ACTIV-2: A Study for Outpatients With COVID-19

Covid19 Clinical Trial

Official title:

Adaptive Platform Treatment Trial for Outpatients With COVID-19 (Adapt Out COVID)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04518410
• Other study ID #: A5401/ACTIV-2
• Secondary ID: 38742
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 19, 2020
• Est. completion date: June 20, 2023

Study information

• Verified date: May 2023
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Drug studies often look at the effect one or two drugs have on a medical condition, and involve one company. There is currently an urgent need for one study to efficiently test multiple drugs from more than one company, in people who have tested positive for COVID-19 but who do not currently need hospitalization. This could help prevent disease progression to more serious symptoms and complications, and spread of COVID-19 in the community.

This study looks at the safety and effectiveness of different drugs in treating COVID-19 in outpatients. In Phase II, participants in the study will be treated with either a study drug or with placebo. In protocol version 7.0, participants in Phase III of the study will be treated with either a study drug or active comparator drug. Participants assigned to the bamlanivimab agent/placebo arm and will have 28 days of intensive follow-up following study drug administration, followed by limited follow-up through 24 weeks in phase II and in phase III. All other investigational agents and their corresponding placebo arms will involve 28 days of intensive follow-up, followed by limited follow-up through 72 weeks in phase II and phase III. Additional study visits may be required, depending on the agent.

Description:

This is a master protocol to evaluate the safety and efficacy of multiple investigational agents aimed at modifying the host immune response to SARS-CoV-2 infection, or directly enhancing viral control in order to limit disease progression.

The study includes both infused and non-infused agents and is a randomized controlled platform that allows agents to be added and dropped during the course of the study for efficient phase II and phase III testing of new agents within the same trial infrastructure.

Version 7 of the protocol provided for blinded phase II evaluation of an investigational agent for superiority to placebo among participants at lower risk of progression to hospitalization or death, regardless of the mode of administration of the agent.

Agents that graduate to phase III after initiation of the protocol version will be evaluated in persons at higher risk for progression to hospitalization or death for non-inferiority to an active comparator (monoclonal antibody cocktail of casirivimab plus imdevimab (REGEN-COV, Regeneron). This active comparator has been shown to be effective in this population in preventing hospitalization or death. When two or more agents are being evaluated in the same phase of the study, the trial design includes sharing of the control group (placebo in phase II and active comparator in phase III) for efficient evaluation of each agent.

Investigational agents will be approved by the Trial Oversight Committee (TOC) for phase II evaluation based on the presence of in vitro data demonstrating promise as anti-SARS-CoV-2 therapeutics in pre-clinical testing, and for which there are suitable pharmacokinetics and safety data from phase I testing, or through clinical or research testing for a different indication, and agent availability. Investigational agents will be included in phase III evaluation based on agent entry criteria for phase III as outlined in the protocol (or by TOC approval based on data available outside ACTIV-2).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4044
• Est. completion date: June 20, 2023
• Est. primary completion date: April 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed informed consent.

• Documentation of laboratory-confirmed SARS-CoV-2 infection, as determined by a molecular (nucleic acid) or antigen test from any respiratory tract specimen (e.g. oropharyngeal, nasopharyngeal (NP), or nasal swab, or saliva) collected =240 hours (10 days) prior to study entry. Laboratory-confirmed SARS-CoV-2 infection outside the US must be conducted at a DAIDS-approved laboratory.

• Able to begin study treatment no later than 7 days from self-reported onset of COVID-19 related symptom(s) or measured fever, where the first day of symptoms is considered symptom day 0 and defined by the self-reported date of first reported sign/symptom from the following list:

• subjective fever or feeling feverish

• cough

• shortness of breath or difficulty breathing at rest or with activity

• sore throat

• body pain or muscle pain/aches

• fatigue

• headache

• chills

• nasal obstruction or congestion

• nasal discharge

• loss of taste or smell

• nausea or vomiting

• diarrhea

• temperature > 38°C (100.4°F)

• One or more of the following signs/symptoms within 24 hours of participating in the study:

• subjective fever or feeling feverish

• cough

• shortness of breath or difficulty breathing at rest or with activity

• sore throat

• body pain or muscle pain/aches

• fatigue

• headache

• chills

• nasal obstruction or congestion

• nasal discharge

• loss of taste or smell

• nausea or vomiting

• diarrhea

• temperature > 38°C (100.4°F)

• Oxygen levels of =92% obtained at rest (adjusted as needed for altitude) by study staff within 24 hours of study entry. For a potential participant who regularly receives chronic supplementary oxygen for an underlying lung condition, their oxygen saturation should be measured while on their standard home oxygen supplementation level.

• Participant must agree not to participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 during the study period until hospitalization or 28 days after the start of the study, whichever occurs first.

• Meet the protocol definition of being at "higher" risk of progression to hospitalization or death (BRII-196/BRII-198).

• In Phase III, meeting the protocol definition of being at "higher" risk of progression to hospitalization or death (SNG001, SAB-185, BMS 986414+BMS 986413)

• For participants of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to study entry by any clinic or laboratory that has a CLIA certification or its equivalent, or by a point of care (POC)/CLIA-waived test. Note: Participants not of reproductive potential are eligible without requiring the use of a contraceptive method (BRII-196/BRII-198. AZD7442 [IV], AZD7442 [IM], SNG001, Camostat, SAB-185, BMS 986414+BMS 986413).

• Participants that engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives. They are strongly advised to inform their non-pregnant sexual partners of reproductive potential to use effective contraceptives for 24 weeks after investigational product is administered. Participants with pregnant partners should use condoms during vaginal intercourse through 24 weeks after investigational agent administration. Participants should refrain from sperm donation for 24 weeks after investigational agent administration (BRII-196/BRII-198, AZD7442 [IV], AZD7442 [IM], SAB-185).

• Participants that engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives for 30 days after investigational agent administration. They are also strongly advised to inform their non-pregnant sexual partners of reproductive potential to sue effective contraceptives for 30 days after investigational agent is administered to the participant. Participants with pregnant partners should use condoms during vaginal intercourse through 30 days after last dose of investigational agent administration. Participants should refrain from sperm donation for 30 days after investigational agent administration (SNG001).

• Participants that engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives. They are also strongly advised to inform their non-regnant sexual partners of reproductive potential to use effective contraceptives from study entry through 90 days after study treatment. Participants with pregnant partners should use condoms during vaginal intercourse from study entry through 90 days after the last dose of the study treatment. Participants should refrain from sperm donation from study entry through 90 days after the last dose of study treatment (Camostat).

• If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use effective contraception for 24 weeks after investigational agent is administered. This would include oral contraceptives, implanted contraceptives, implanted contraceptives, intrauterine devices, and barrier methods.

• If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use highly effective contraception for 24 weeks after investigational agent is administered (AZD7442 [IV], AZD7442 [IM], SAB-185).

• If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use effective contraception for 30 days after investigational agent is administered (SNG001).

• If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use effective contraception for 90 days after the last dose of treatment (Camostat).

• If participating in sexual activity that could lead to pregnancy, participants who are of reproductive potential must agree to use highly effective contraception for at least 48 weeks after the investigational agent is administered (BMS 986414+BMS 986413).

Exclusion Criteria:

• History of or current hospitalization for COVID-19.

• For the current SARS-CoV-2 infection, any positive SARS-CoV-2 nucleic acid or antigen tests from any respiratory tract specimen collected > 240 hours prior to study entry.

• Current need for hospitalization or immediate medical attention.

• Use of any prohibited medication listed in the protocol and/or use of systemic or inhaled steroids for the purpose of COVID-19 treatment (new or increased dose from chronic baseline) within 30 days prior to study.

• Receipt of convalescent COVID-19 plasma or other antibody-based anti-SARS-CoV-2 treatment or prophylaxis at any time prior to study entry.

• Receipt of other investigational treatments for SARS-CoV-2 any time before participating in the study (not including drugs approved and taken for other conditions/diseases or COVID-19 vaccines).

• Known allergy/sensitivity or hypersensitivity to study drug or placebo.

• Any condition requiring surgery up to 7 days before participating in the study, or that is considered life threatening up to 30 days before participating in the study.

• Currently pregnant or breastfeeding (BRII-196/BRII-198, AZD7442 [IV], AZD7442 [IM], SNG001, Camostat, SAB-185, BMS 986414+BMS 986413).

• In phase II, meeting the protocol definition of being at "higher" risk of progression to hospitalization or death (AZD7442 [IV], AZD7442 [IM], SNG001, Camostat, SAB-185, BMS 986414+BMS 986413).

• Inflammatory skin conditions that compromise the safety of intramuscular (IM) injections, or other overlying skin conditions or tattoos that would preclude the assessment of injection site reactions, per the discretion of the investigator (AZD7442 [IM]).

• Inflammatory skin conditions that compromise the safety of subcutaneous (SC) injections, or other overlying skin conditions or tattoos that would preclude the assessment of infection site reactions, per the discretion of the investigator (BMS 986414+BMS 986413).

• History of coagulopathy which, in the opinion of the investigator, would preclude IM injection, or use of oral or injectable anticoagulants (protocol provides more information on prohibited medications) (AZD7442 [IM]).

• Use of or need for chronic supplemental oxygen (SNG001).

• Known severe liver disease prior to enrollment (defined as ALT or AST > 5 times upper limit of normal or end stage liver disease with Child-Pugh Class C or Child-Pugh-Turcotte score = 10) (Camostat).

• Known severe kidney disease prior to enrollment (defined as estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m² or on renal-replacement therapy such as peritoneal dialysis or hemodialysis (Camostat)

Other investigational drug protocol-defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Coronavirus
• Coronavirus Infections
• COVID-19
• Covid19

Intervention

Biological:
• bamlanivimab 7000mg
Administered by single IV infusion. Participants are no longer being randomized to this intervention.
• BRII-196+BRII-198
1000 mg (BRII-196)/1000 mg (BRII-198) combination therapy. Administered by consecutive IV infusions as single dose. Participants are no longer being randomized to this intervention.
• AZD7442 (IV)
300 mg AZD7442 (150 mg AZD8895 + 150 mg AZD1061). Administered by IV infusion as single dose. Participants are no longer being randomized to this intervention.
• AZD7442 (IM)
Administered intramuscularly as 2 separate injections sequentially (300 mg AZD8895 then 300 mg AZD1061) for one dose. Injections administered in the side of the thigh, one injection in each thigh. Participants are no longer being randomized to this intervention.

Drug:
• SNG001
1.3 mL solution administered once daily for 14 days using Aerogen Ultra nebulizer (inhalation device). Participants are no longer being randomized to this intervention.
• Camostat
200 mg (2 x 100 mg) film-coated tablets administered orally every 6 hours for 7 days. Participants are no longer being randomized to this intervention.

Biological:
• BMS-986414 + BMS-986413
Administered subcutaneously (SC) as 4 separate injections for one dose (two injections of C135-LS 200mg and two injections of C144-SL 200mg). Participants are no longer being randomized to this intervention.
• SAB-185 (3,840 Units/kg)
Administered by IV infusion as single dose. Participants are no longer being randomized to this intervention.
• SAB-185 (10,240 Units/kg)
Administered by IV infusion as single dose. Participants are no longer being randomized to this intervention.

Drug:
• CASIRIVIMAB + IMDEVIMAB
600 mg casirivimab and 600 mg imdevimab, administered together as single IV infusion as one-time dose at study entry. Participants are no longer being randomized to this intervention.
• Placebo for Bamlanivimab 7000mg
Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
• Placebo for Bamlanivimab 700mg
Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
• Placebo for BRII-196+BRII-198
Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
• Placebo for SNG001
Trisodium citrate dihydrate, di-sodium hydrogen-phosphate, sodium dihydrogen-phosphate dihydrate, racemic methionine (DL-methionine) and water. 1.3 mL solution administered once daily for 14 days using Aerogen Ultra nebulizer (inhalation device). Participants are no longer being randomized to this intervention.
• Placebo for Camostat
200 mg (2 x 100 mg) film-coated tablets administered orally every 6 hours for 7 days. Participants are no longer being randomized to this intervention.
• Placebo for SAB-185 (low dose)
Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
• Placebo for BMS-986414 + BMS-986413
Administered SC as 4 separate injections for one dose. Participants are no longer being randomized to this intervention.
• Placebo for AZD7442 (IV)
Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
• Placebo for AZD7442 (IM)
Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.
• Placebo for SAB-185 (high dose)
Commercially available 0.9% sodium chloride solution. Participants are no longer being randomized to this intervention.

Biological:
• bamlanivimab 700mg
Administered by single IV infusion. Participants are no longer being randomized to this intervention.

Locations

Country	Name	City	State
Argentina	Fundación Sanatorio Güemes (Site 3001), Francisco Acuña de Figueroa 1240	Buenos Aires	Ciudad Autónoma De Buenos Aires
Argentina	Clínica Adventista Belgrano (Site 3007), Estomba 1710	Ciudad Autonoma de Buenos Aires
Argentina	Instituto Médico Platense (Site 3011), Avenida 51 335	La Plata	Buenos Aires
Argentina	Instituto Ave Pulmo (Site 3006), Carlos M. Alvear 3345	Mar Del Plata
Argentina	Hospital Universitario Austral (Site 3004), Av. Juan Domingo Peron, Derqui	Pilar
Argentina	Instituto Médico Río Cuarto (Site 3005), Hipólito Yrigoyen 1020	Río Cuarto	Córdoba
Argentina	Instituto Médico de la Fundación Estudios Clínicos (Site 3009), Italia 428	Rosario	Santa Fe
Brazil	Hospital Das Clinicas Da Universidade Federal de Minas Gerais (Site 4001), Avenida Alfredo Balena 190	Belo Horizonte	Minas Gerais
Brazil	SOM Federal University Minas Gerais Brazil (Site 4002), Avenida Alfredo Balena 190	Belo Horizonte	Minas Gerais
Brazil	Hospital Dia do Pulmão (Site 4007), Rua Engenheiro Paul Werner, 1141	Blumenau	Santa Catarina
Brazil	L2 Ip - Instituto de Pesquisas Clinicas Ltda (Site 4008), SGAS 613, Conjunto E, Lote 95, Sala 6	Brasília	Distrito Federal
Brazil	Hospital Nossa Senhora da Conceicao (Site 4004), Avenida Francisco Trein 596	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto (Site 4003), Avenida Bandeirantes 3900, Campus Universitário	Ribeirão Preto	São Paulo
Brazil	Instituto de Pesquisa Clínica Evandro Chagas (Site 4005), Avenida Brasil, 4365	Rio De Janeiro
Brazil	Hospital E Maternidade Celso Pierro (Site 4006), Avenue John Boyd Dunlop S/n	São Paulo
Canada	Medical Arts Health Research Group (Site 2003), 360-1855 Kirschner Rd.	Kelowna	British Columbia
Guatemala	Centro Medico Militar (Site 9401), Finca El Palomar, Acatan, Sta. Rosita Zona 16	Ciudad De Guatemala
Mexico	Hospital Civil De Culiacan (Site 6011), Avenida Álvaro Obregón 1422	Culiacán	Sinaloa
Mexico	Neurociencias Estudios Clinicos S.C. (Site 6008), Boulevard Alfonso G. Calderon, 2193 int 2 A desarrollo urbano 3 rios	Culiacán	Sinaloa
Mexico	Centro de Investigación Farmacéutica Especializada de Occidente (Site 6006), Av. Vallarta 1670, Piso 2 PH1, Colonia Americana	Guadalajara	Jalisco
Mexico	Instituto Jalisciense de Investigacion Clinica SA de CV (Site 6005), Penitenciaria Numero 20, Colonia Centro	Guadalajara	Jalisco
Mexico	Eme Red Hospitalaria (Site 6010), Calle 33 No. 496	Mérida	Yucatán
Mexico	Kohler and Milstein Research (Site 6013), Avenida Colón 197, García Ginerés	Mérida	Yucatán
Mexico	Oaxaca Site Management Organization (Site 6004), Calle Humboldt 302, Colonia Centro	Oaxaca	Distrito Federal
Mexico	CIMAB SA de CV (Site 6002), Francisco I Madero 270 Sur	Torreon	Coahuila
Philippines	De La Salle Health Sciences Institute (Site 9504), Gov. Mangubat Avenue	Cavite City	Cavite
Philippines	Makati Medical Center (Site 9502), No. 2 Amorsolo Street, Legaspi Village	Makati City	National Capital Region
Philippines	Asian Hospital and Medical Center (Site 9503), 2205 Civic Drive	Muntinlupa	National Capital Region
Puerto Rico	Puerto Rico AIDS Clinical Trials Unit (Site 1024), Proyecto ACTU Biomedical Building II	San Juan
South Africa	Worthwhile Clinical Trials (Site 9214), No. 1 Mowbray Avenue	Benoni	Gauteng
South Africa	Durban International Clinical Research Site (Site 9208), Sidmouth Avenue	Durban	Kwazulu - Natal
South Africa	TASK Eden (Site 9218), G, 4 Victoria St.	George
South Africa	CLINRESCO, ARWYP Medical Suites (Site 9209), 22 Pine Avenue	Johannesburg
South Africa	Helen Joseph Hospital (Site 9201), Perth Road	Johannesburg	Gauteng
South Africa	Roodepoort Medicross (Site 9220), 54 Ontdekkers Road	Johannesburg	Gauteng
South Africa	Soweto ACTG CRS (Site 9203), Chris Hani Road	Johannesburg	Gauteng
South Africa	The Aurum Institute Tembisa Clinical Research Site (Site 9217), Cnr Flint Mazibuko / Rev RTJ Namane Drive	Johannesburg	Gauteng
South Africa	Peermed Clinical Trial Center (Site 9215), Corner of Voortrekker and Monument Roads	Kempton Park	Ekurhuleni, Gauteng
South Africa	The Aurum Institute Klerksdorp Clinical Research Center (Site 9204), Corner Margaretha Prinsloo St. and O.R. Tambo St.	Klerksdorp	North-West
South Africa	Mzansi Ethical Research Centre (Site 9212), 184 Cowen Ntuli Street, Steve Tschwete	Mpumalanga
South Africa	Global Clinical Trials Sunnyside (Site 9216), 175 Steve Biko Street	Pretoria
South Africa	Setshaba Research Centre (Site 9205), 2088 Block H	Pretoria	Gauteng
South Africa	The Aurum Institute Rustenburg Clinical Research Site (Site 9202), 50 Steen St., c/o Pretorius St.	Rustenburg	North-West
South Africa	Into Research (Site 9210), Totius Street	Tshwane	Gauteng
South Africa	Welkom Clinical Trial Centre (Site 9211), 189 Power Road	Welkom	Matjhabeng, Free State
United States	Omnibus Clinical Research (Site 1253), 3340 W. Ball Road, Ste. I	Anaheim	California
United States	Pinnacle Research Group (Site 1082), 321 E. 10th Street	Anniston	Alabama
United States	North Alabama Research Center LLC (Site 1194), 721 W. Market St., Ste. B	Athens	Alabama
United States	Agile Clinical Rsearch Trials, LLC (Site 1051), 750 Hammond Drive	Atlanta	Georgia
United States	Rare Disease Research, LLC. (Site 1248), 1891 Howell Mill Rd.NW, Ste. B	Atlanta	Georgia
United States	The Ponce de Leon Center (site 1015), 341 Ponce De Leon Avenue Northeast	Atlanta	Georgia
United States	University of Colorado (Site 1007), 12401 East 17th Avenue	Aurora	Colorado
United States	Franco A. Felizarta MD (Site 1174), 3535 San Dimas St.	Bakersfield	California
United States	Baltimore VA Medical Center (Site 1258), 10 N. Greene St.	Baltimore	Maryland
United States	Johns Hopkins University (Site 1006), 1830 East Monument Street	Baltimore	Maryland
United States	Saint Hope Foundation Inc. (Site 1100), 6800 West Loop Street, Ste. 560	Bellaire	Texas
United States	University of Alabama at Birmingham (Site 1005), 908 20th Street South	Birmingham	Alabama
United States	South Texas Medical Research Institute, Inc./TTS Research (Site 1198), 1420 River Road	Boerne	Texas
United States	Beth Israel Deaconess Medical Center (Site 1166), 110 Francis Street	Boston	Massachusetts
United States	Brigham and Women's Hospital - Therapeutics Clinical Research Site (Site 1023), 75 Francis Street	Boston	Massachusetts
United States	Massachusetts General Hospital (Site 1016), 55 Fruit Street	Boston	Massachusetts
United States	Imagine Research of Palm Beach County (Site 1157), 709 S. Federal Hwy., Ste. 2	Boynton Beach	Florida
United States	Bozeman Health Deaconess Hospital (Site 1115), 931 Highland Blvd, Ste. 3103	Bozeman	Montana
United States	Bradenton Research Center Inc. (Site 1109), 3924 9th Ave. W	Bradenton	Florida
United States	Synergy Healthcare (Site 1099), 300 Riverside Drive E., Ste. 1350	Bradenton	Florida
United States	Bronx Prevention Research Center (Site 1108), 390 East 158th Street	Bronx	New York
United States	Jacobi Medical Center (Site 1105), 1400 Pelham Parkway South	Bronx	New York
United States	James J. Peters VA Medical Center (Site 1053), 130 West Kingsbridge Road	Bronx	New York
United States	Lincoln Hospital (Site 1092), 249 East 149th Street	Bronx	New York
United States	Urban Health Plan, Inc. (Site 1243), 1065 Southern Blvd	Bronx	New York
United States	Maimonides Medical Center (Site 1138), 4802 10th Avenue	Brooklyn	New York
United States	Investigators Research Group, LLC. (Site 1170), 321 E. Northfield Dr., Ste. 100	Brownsburg	Indiana
United States	PanAmerican Clinical Research, LLC. (Site 1069), 1416 Palm Blvd.	Brownsville	Texas
United States	University at Buffalo, Emergency Medicine (Site 1172), 77 Goodell Street	Buffalo	New York
United States	Balanced Life Health Care Solutions/SKYCRNG (Site 1191), 2033 Buford Hwy., Ste. 109	Buford	Georgia
United States	Metro Infectious Disease Consultants (Site 1106), 901 McClintock Dr., Ste. 201	Burr Ridge	Illinois
United States	Mercury Street Medical Group (Site 1074), 300 W. Mercury St.	Butte	Montana
United States	Clearview Medical Research LLC. (Site 1251), 2714 Hidaway Ave., Ste. 103	Canyon Country	California
United States	University of North Carolina at Chapel Hill (Site 1001), 130 Mason Farm Rd., Bioinformatics Bldg, 2nd Floor	Chapel Hill	North Carolina
United States	Carolina Clinical Research (Site 1167), 9040 Nations Ford Rd.	Charlotte	North Carolina
United States	Chicago Clinical Research Institute (Site 1132), 611 W. Roosevelt Rd.	Chicago	Illinois
United States	Great Lakes Clinical Trials (Site 1049), 5149 N. Ashland Ave.	Chicago	Illinois
United States	Northwestern University (Site 1025), 645 North Michigan Ave	Chicago	Illinois
United States	Rush University Medical Center (Site 1017), 600 Paulina St.	Chicago	Illinois
United States	University of Chicago (Site 1064), 5841 S. Maryland Ave.	Chicago	Illinois
United States	University of Illinois at Chicago (Site 1147), 835 South Wood Street	Chicago	Illinois
United States	The Christ Hospital (Site 1119), 2123 Auburn Avenue	Cincinnati	Ohio
United States	Case Western Reserve University (Site 1033), 2061 Cornell Road	Cleveland	Ohio
United States	MetroHealth Medical Center (Site 1195), 2500 Metrohealth Dr.	Cleveland	Ohio
United States	Medtrial, LLC (Site 1134), 1718 Saint Julian Pl., Ste. 2	Columbia	South Carolina
United States	University of Missouri Health Care System (Site 1224), 1 Hospital Drive	Columbia	Missouri
United States	IACT Health (Site 1035), 800 Talbotton Road	Columbus	Georgia
United States	Ohio State University Medical Center (Site 1020), 480 Medical Center Drive	Columbus	Ohio
United States	Cullman Clinical Trials (Site 1140), 501 Clark St. NE.	Cullman	Alabama
United States	Trinity Health and Wellness Center (Site 1030), 219 Sunset Avenue	Dallas	Texas
United States	UT Southwestern HIV/ID Clinical Trials Unit (Site 1208), 1936 Amelia Court	Dallas	Texas
United States	Cardiology Physicians, P.A. (Site 1180), 305 Memorial Medical Pkwy., Ste. 301	Daytona Beach	Florida
United States	Vida Clinical Studies (Site 1244), 3815 Pelham Street	Dearborn	Michigan
United States	Midland Florida Clinical Research Center LLC (Site 1130), 665 Peachwood Drive	DeLand	Florida
United States	Research Carolina Elite (Site 1247), 7480 Waterside Loop Road, Suite 201	Denver	North Carolina
United States	Integrity Clinical Research (Site 1214), 3901 NW 79th Ave.	Doral	Florida
United States	Universal Axon Clinical Research (Site 1077), 3650 NW 82nd Ave.	Doral	Florida
United States	Doylestown Hospital (Site 1122), 595 W. State Street	Doylestown	Pennsylvania
United States	Clintheory (Site 1254), 4300 Pleasant Hill Road	Duluth	Georgia
United States	Duke University Medical Center (Site 1041), 40 Duke Medicine Circle	Durham	North Carolina
United States	Doctors Hospital at Renaissance Health Institute for Research and Development (Site 1145), 5323 S. McColl Rd.	Edinburg	Texas
United States	Inova Fairfax Medical Campus (Site 1029), 3300 Gallows Road	Falls Church	Virginia
United States	Sanford Health (Site 1084), 801 Broadway N.	Fargo	North Dakota
United States	Revive Research Institute (Site 1257), 32255 Northwestern Hwy.	Farmington Hills	Michigan
United States	Flushing Hospital Medical Center (Site 1067), 4500 Parsons Blvd	Flushing	New York
United States	EMINAT Research (Site 1202), 2500 E. Commercial Blvd.	Fort Lauderdale	Florida
United States	Holy Cross Health (Site 1072), 4725 North Federal Highway	Fort Lauderdale	Florida
United States	Clinical Trials Center of Middle Tennessee (Site 1183), 100 Covey Drive	Franklin	Tennessee
United States	St. Jude Heritage Medical Group (Site 1093), 2151 N. Harbor Blvd.	Fullerton	California
United States	North Florida / South Georgia Veterans Health System (Site 1133), 1601 SW Archer Rd.	Gainesville	Florida
United States	University of Florida (Site 1047), 1600 SW. Archer Rd.	Gainesville	Florida
United States	Sealy Institute for Vaccine Sciences Clincial Trials Program (Site 1044), 400 Harborside Drive	Galveston	Texas
United States	NW FL Clinical Research Group, LLC. (Site 1046), 400 Gulf Breeze Parkway	Gulf Breeze	Florida
United States	MedPharmics, LLC. (Site 1032), 15190 Community Rd.	Gulfport	Mississippi
United States	Memorial Hospital at Gulfport (Site 1104), 4500 13th Street	Gulfport	Mississippi
United States	Hannibal Clinic (Site 1129), 100 Medical Drive	Hannibal	Missouri
United States	AGA Clinical Trials (Site 1026), 900 West 49th Street	Hialeah	Florida
United States	Best Quality Research, Inc. (Site 1237), 2387 W. 68th St., Ste. 403	Hialeah	Florida
United States	Community Research of South Florida (Site 1197), 7100 W. 20th Ave., Ste. 403	Hialeah	Florida
United States	Indago Research and Health Center (Site 1050), 3700 W. 12th Ave., Ste. 300	Hialeah	Florida
United States	New Generation Medical Research (Site 1204), 7600 W. 20th Ave., Ste. 106	Hialeah	Florida
United States	Innovative Health Medical Center (Site 1222), 6750 Taft Street	Hollywood	Florida
United States	John A. Burns School of Medicine UH Clinics at Kakaako (Site 1177), 651 Ilalo St.	Honolulu	Hawaii
United States	Dynamic Medical Research Group (Site 1081), 8314 Southwest Fwy	Houston	Texas
United States	Fairway Medical Clinic (Site 1156), 4910 Telephone Road	Houston	Texas
United States	Houston Methodist Hospital (Site 1123), 6565 Fannin Street	Houston	Texas
United States	Lyndon B. Johnson Hospital (Site 1014), 5656 Kelley Street	Houston	Texas
United States	Rheumatology Center of Houston (Site 1252), 1200 Binz St., Ste. 1495	Houston	Texas
United States	University of Texas Health Science Center at Houston (Site 1055), 6431 Fannin Street, Ste. 2.112	Houston	Texas
United States	Houston Heart and Vascular Associates (Site 1215), 1485 FM 1960 Bypass R. E., Ste. 100	Humble	Texas
United States	Hershel Woody Williams VA Medical Center (Site 1128), 1540 Spring Valley Drive	Huntington	West Virginia
United States	Snake River Research, PLLC (Site 1120), 2900 Cortez Ave.	Idaho Falls	Idaho
United States	Roudebush VA Medical Center (Site 1217), 550 University Blvd	Indianapolis	Indiana
United States	Mayo Clinic Jacksonville (Site 1149), 4500 San Pablo Rd. S.	Jacksonville	Florida
United States	University of Florida Jacksonville (Site 1039), 655 West 8th Street	Jacksonville	Florida
United States	Jamaica Hospital Medical Center (Site 1066), 8900 Van Wyck Expressway	Jamaica	New York
United States	Jasper Summit Research, LLC. (Site 1056), 1280 Summit	Jasper	Alabama
United States	University of Kansas Medical Center (Site 1042), 3901 Rainbow Boulevard	Kansas City	Kansas
United States	EvergreenHealth (Site 1080), 12040 NE 128th Street, Ste MS-77	Kirkland	Washington
United States	University of California San Diego (Site 1160), 9350 Campus Point Drive, Perlman Cancer Cancer	La Jolla	California
United States	Fadi A. Haddad, MD, Inc. (Site 1146), 8860 Center Dr., Ste. 320	La Mesa	California
United States	Atella Clinical Research (Site 1111), 5451 La Palma Avenue	La Palma	California
United States	Las Vegas Medical Research (Site 1048), 8530 W. Sunset Rd.	Las Vegas	Nevada
United States	Loma Linda University Health (Site 1110), 11374 Mountain View, Dover Bldg, Ste. C	Loma Linda	California
United States	Science 37, Inc. (Site 1124), 12121 Bluff Creek Dr., Ste. 100	Los Angeles	California
United States	UCLA CARE Center (Site 1003), 11075 Santa Monica Blvd., Suite 100	Los Angeles	California
United States	University of Southern California (Site 1057), 1300 N. Mission Rd., Rm 349	Los Angeles	California
United States	VA Northern California Health Care System (NAVREF) (Site 1137), 10535 Hospital Way	Mather	California
United States	SMS Clincial Research, LLC. (Site 1060), 1210 N. Galloway Ave.	Mesquite	Texas
United States	MedPharmics (Site 1065), 3800 Houma Blvd.	Metairie	Louisiana
United States	Advance Medical Research Center (Site 1193) 330 SW. 27th Ave., Ste. 701	Miami	Florida
United States	Allied Biomedical Research Institute (Site 1227), 7100 SW. 47th St., Ste. 220	Miami	Florida
United States	Clintex Research Group, Inc. (Site 1231), 590 SW. 27th Ave.	Miami	Florida
United States	D&H National Research Centers (Site 1205), 8485 Bird Road	Miami	Florida
United States	Florida International Medical Research (Site 1239), 1890 S. Red Rd., Ste. 103	Miami	Florida
United States	Gonzalez MD & Aswad MD Health Services (Site 1238), 3401 NW. 7th Street	Miami	Florida
United States	Miami Clinical Research (Site 1089), 2400 SW. 69th Ave.	Miami	Florida
United States	Miami Dade Medical Research Institute, LLC (Site 1223), 8955 SW. 87th Ct.	Miami	Florida
United States	Pro Live Medical Research Corp (Site 1219), 12781 SW. 42nd Street	Miami	Florida
United States	Research Institute of South Florida, Inc. (Site 1201), 9835 SW. 72nd Street, Ste. 201	Miami	Florida
United States	RM Medical Research, Inc. (Site 1230), 10346 W. Flagler St.	Miami	Florida
United States	University of Miami Miller School of Medicine CoVID Unit (Site 1068), 1425 NW. 10th Ave.	Miami	Florida
United States	QC Trials (Site 1117), 300 W. 41st Street, Ste. 203	Miami Beach	Florida
United States	Lakes Research (Site 1037), 5801 NW 151 Street	Miami Lakes	Florida
United States	Savin Medical Group, LLC. (Site 1212), 5789B NW. 151st Street	Miami Lakes	Florida
United States	Amber Clinical Research, LLC. (Site 1206), 9000 NE. 2nd Avenue	Miami Shores	Florida
United States	Medical College of Wisconsin, Inc. (Site 1036), 8701 Watertown Plank Road	Milwaukee	Wisconsin
United States	Vida Clinical Studies (Site 1246), 5757 West Oklahoma Avenue	Milwaukee	Wisconsin
United States	Central Valley Research, LLC (Site 1085), 400 E. Orangeburg Ave., Ste. 5	Modesto	California
United States	Clinical Trials of America, LLC. (Site 1245) 3201 Armand Street	Monroe	Louisiana
United States	Carteret Medical Group, LLC. (Site 1249), 302 Medical Park Ct.	Morehead City	North Carolina
United States	West VA University, Mary Babb Randolph Cancer Center (Site 1178), 1 Medical Center Drive	Morgantown	West Virginia
United States	Vanderbilt Therapeutics Clinical Research (Site 1013), Vanderbilt Health One Hundred Oaks, 719 Thompson Ln., Ste 47183	Nashville	Tennessee
United States	Louisiana State University Health Sciences Center (Site 1153), 2000 Canal Street	New Orleans	Louisiana
United States	New Orleans Adolescent Trials Unit (Site 1028), 1440 Canal St., Suite 904	New Orleans	Louisiana
United States	Ochsner Clinic Foundation (Site 1218), 1514 Jefferson Highway	New Orleans	Louisiana
United States	Columbia Partnership for Prevention and Control of HIV/AIDS CTU (Site 1019), Columbia University Irving Medical Center, Department of Medicine - Division of Infectious Diseases, 180 Fort Washington Avenue, HP6 - Rm 604	New York	New York
United States	Cornell Clinical Trials Unit (Site 1011), NewYork-Presbyterian Hospital-Weill Cornell Medical Center, 525 East 68th Street	New York	New York
United States	Hoag Memorial Hospital Presbyterian (Site 1200), 1 Hoag Dr.	Newport Beach	California
United States	One Health Research Clinic, Inc. (Site 1250), 5880 Live Oak Pkwy, Ste. 160	Norcross	Georgia
United States	Bravo Health Care Center (Site 1221), 1440 79 Street	North Bay Village	Florida
United States	Valley Clinical Research, Inc. (Site 1059), 18433 Roscoe Blvd., Ste 210	Northridge	California
United States	Cincinnati CRS (Site 1004), University of Cincinnati, University Hospital, 200 Albert Sabin Way	Ohio City	Ohio
United States	Quality Clinical Research (Site 1112), 10040 Regency Circle	Omaha	Nebraska
United States	University of California Irvine (Site 1083), 843 Health Sciences Road	Orange	California
United States	Clintheory (Site 1203), 7350 Sandlake Commons Blvd.	Orlando	Florida
United States	Orlando Immunology Center (Site 1045), 1707 North Mills Avenue	Orlando	Florida
United States	FOMAT Medical Research (Site 1136), 300 South A Street	Oxnard	California
United States	IMIC, Inc. (Site 1141), 18320 Franjo Rd	Palmetto Bay	Florida
United States	Family Clinical Trials (Site 1236), 1601 N. Palm Ave., Ste. 102	Pembroke Pines	Florida
United States	University of Pennsylvania (Site 1031), 3400 Spruce Street	Philadelphia	Pennsylvania
United States	Absolute Clinical Research, LLC. (Site 1186), 7725 North 43rd Avenue, Ste. 211	Phoenix	Arizona
United States	The University of Pittsburgh (Site 1018), 3471 5th Ave.	Pittsburgh	Pennsylvania
United States	Veterans Affairs Pittsburgh Healthcare System (Site 1070), University Drive C.	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Center for Health Research (Site 1079), 3800 N. Interstate Ave.	Portland	Oregon
United States	Oregon Health and Science University (Site 1259), 3181 SW. 10th Avenue	Portland	Oregon
United States	Portland VA Medical Center (Site 1131), 3710 SW US Veterans Hospital Rd.	Portland	Oregon
United States	Providence Portland Medical Center (Site 1098), 4805 NE. Glisan Street	Portland	Oregon
United States	Canton-Potsdam Hospital (Site 1076), 50 Leroy Street	Potsdam	New York
United States	The Miriam Hospital Clinical Research Site (1142), 164 Summit Avenue	Providence	Rhode Island
United States	Eisenhower Medical Center (Site 1040), 39000 Bob Hope Drive	Rancho Mirage	California
United States	American Indian Clinical Trials Research Network (Site 1148), 717 Meade Street	Rapid City	South Dakota
United States	Epic Medical Research, LLC (Site 1233), 106 Plaza Drive	Red Oak	Texas
United States	Paradigm Research (Site 1150), 3652 Eureka Way	Redding	California
United States	Clinical Research Partners LLC (Site 1196), 7110 Forest Ave., Ste. 201	Richmond	Virginia
United States	Riverside Medical Clinic (Site 1232), 7117 Brockton Ave.	Riverside	California
United States	University of Rochester (Site 1010), 601 Elmwood Ave	Rochester	New York
United States	University of California Davis Medical Center (Site 1097), 2315 Stockton Blvd.	Sacramento	California
United States	Washington University School of Medicine (Site 1008), 620 South Taylor, Suite 200	Saint Louis	Missouri
United States	San Antonio Military Medical Center (Site 1173), 3551 Roger Brooke Dr.	San Antonio	Texas
United States	Premier Urgent Care Centers of California, Inc. (Site 1176), 284 E. Highland Ave.	San Bernardino	California
United States	University of California San Diego (Site 1002), 220 Dickinson Street	San Diego	California
United States	VA San Diego Health System (Stie 1127), 3350 La Jolla	San Diego	California
United States	Zion Medical Center (Site 1063), 4647 Zion Avenue	San Diego	California
United States	San Francisco Research Institute (Site 1210), 2435 Ocean Ave.	San Francisco	California
United States	University of California San Francisco (Site 1009), 995 Potrero Ave., Building 80, Ward 84	San Francisco	California
United States	AXCES Research Group (Site 1152), 531 Harkle Road	Santa Fe	New Mexico
United States	Physician Care Clinical Research, LLC. (Site 1242), 1617 S. Tuttle Ave., Ste. 1A	Sarasota	Florida
United States	University of Washington ACTU (Site 1012), Harborview Medical Center, 325 9th Ave.	Seattle	Washington
United States	Bassetti Medical Research, Inc. (Site 1158), 5825 US Highway 27 N.	Sebring	Florida
United States	Walter Reed Army Institute of Research (Site 1118), 503 Robert Grant Ave.	Silver Spring	Maryland
United States	Sanford USD Medical Center (Site 1078), 1305 W. 18th St.	Sioux Falls	South Dakota
United States	Renew Health Clinical Research, LLC. (Site 1161), 1550 Janmar Rd.	Snellville	Georgia
United States	Providence Medical Research Center (Site 1075), 105 W. 8th Ave., Ste. 6050W	Spokane	Washington
United States	STAT Research (Site 1107), 66 Remick Blvd.	Springboro	Ohio
United States	Stanford University (Site 1213), 1201 Welch Road	Stanford	California
United States	Revival Research Corporation (Site 1256), 13409 East 14 Mile Road	Sterling Heights	Michigan
United States	SUNY Stony Brook NICHD (Site 1094), HSC L-02, Rm. 142 C	Stony Brook	New York
United States	UConn - Institute for Collaboration on Health (Site 1169), 2006 Hillside Rd., Unit 1248	Storrs	Connecticut
United States	DBC Research (Site 1188), 7707 N. University Dr., Ste. 106	Tamarac	Florida
United States	ETNA Medical Center (Site 1225), 7401 N. University Drive	Tamarac	Florida
United States	Moore Clinical Research, Inc. (Site 1164), 4257 W. Kennedy Blvd.	Tampa	Florida
United States	Tampa General Hospital Family Care Center Healthpark (Site 1088), 5802 N. 30th Street	Tampa	Florida
United States	Millennium Clinical Trials (Site 1260), 550 Saint Charles Dr., Ste. 208	Thousand Oaks	California
United States	Office of Ramesh V. Nathan, MD (Site 1073), 2220 Lynn Rd., Ste. 301	Thousand Oaks	California
United States	Harbor UCLA (Site 1022), 1124 West Carson Street	Torrance	California
United States	University of Arizona (Site 1043), 1501 N. Campbell Ave., Rm. 6410	Tucson	Arizona
United States	Ascension St. John Clinical Research Institute (Site 1090), 1725 East 19th Street	Tulsa	Oklahoma
United States	AIDS Research and Treatment Center of the Treasure Coast (Site 1095), 981 37th Place	Vero Beach	Florida
United States	Infectious Disease Consultants of the Treasure Coast (Site 1171), 3735 11th Cir., Ste. 201	Vero Beach	Florida
United States	Whitman-Walker Health (Site 1027), 1337 R Street NW.	Washington	District of Columbia
United States	Allegiance Research Specialists (Site 1162), 2645 N. Mayfair Rd., Ste. 200	Wauwatosa	Wisconsin
United States	Clinovacare Medical Clinical Research Center (Site 1211), 160 Medical Circle Suite D	West Columbia	South Carolina
United States	Triple O Research Institute PA (Site 1121), 2580 Metrocentre Blvd., Ste. 4	West Palm Beach	Florida
United States	Allianz Research Institute Inc. (Site 1159), 14120 Beach Blvd., Ste. 101	Westminster	California
United States	Wake Forest University Health Sciences (Site 1038), 1 Medical Center Boulevard	Winston-Salem	North Carolina
United States	University of Massachusetts Medical School (Site 1054), 55 Lake Avenue N.	Worcester	Massachusetts

Sponsors (9)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	AIDS Clinical Trials Group, AstraZeneca, Brii Biosciences Limited, Bristol-Myers Squibb, Eli Lilly and Company, SAb Biotherapeutics, Inc., Sagent Pharmaceuticals, Synairgen Research Ltd.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Guatemala,  Mexico,  Philippines,  Puerto Rico,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	COVID-19 Symptom Duration (Phase 2)	Bamlanivimab arms: Symptom duration=max. duration (days) across targeted symptoms including: feeling feverish, cough, shortness of breath/difficulty breathing at rest/with activity, sore throat, body pain/muscle pain/aches, fatigue, headache, chills, nasal obstruction/congestion, nasal discharge, nausea, vomiting, and diarrhea. Subjects who die on/before day 28 assigned symptom duration 29 days.; No scale. Min. value: 0 Days, Max. Value 29 Days. Higher value=worse health condition.; Non-Bamlanivimab arms: 13 symptoms (as for Bamlanivimab) scored daily as absent (score 0), mild (score 1), moderate (score 2) or severe (score 3). Symptom duration=time (days) from Day 0 (pre-treatment) to first of two consecutive days when all symptoms scored moderate/severe at Day 0 (pre-treatment) are scored mild/absent, AND all symptoms scored mild/absent at Day 0 (pre-treatment) are scored absent.; No scale. Min. value: 0 Days, Max. Value 26 Days. Higher value=worse health condition.	Up to Day 28
Primary	Quantification of SARS-CoV-2 RNA (Phase 2)	Bamlanivimab Agent arms: Measured as Detected or Undetected from staff-collected NP (nasopharyngeal) swabs. Lower Limit of Detection is 1.4 (log 10 copies/ml).; Non-Bamlanivimab Agent arms: Measured as below Lower Limit of Quantification (LLoQ) or at/above LLoQ from staff-collected NP (nasopharyngeal) swabs. Lower Limit of Quantification is 2 (log 10 copies/ml).; SNG001 and SNG001 Pooled Placebo arm each exclude 6 participants, due to unsuitable sample specimen conditions.	Day 3
Primary	Quantification of SARS-CoV-2 RNA (Phase 2)	Bamlanivimab Agent arms: Measured as Detected or Undetected from staff-collected NP (nasopharyngeal) swabs. Lower Limit of Detection is 1.4 (log 10 copies/ml).; Non-Bamlanivimab Agent arms: Measured as below Lower Limit of Quantification (LLoQ) or at/above LLoQ from staff-collected NP (nasopharyngeal) swabs. Lower Limit of Quantification is 2 (log 10 copies/ml).	Day 7
Primary	Quantification of SARS-CoV-2 RNA (Phase 2)	Bamlanivimab Agent arms: Measured as Detected or Undetected from staff-collected NP (nasopharyngeal) swabs. Lower Limit of Detection is 1.4 (log 10 copies/ml).; Non-Bamlanivimab Agent arms: Measured as below Lower Limit of Quantification (LLoQ) or at/above LLoQ from staff-collected NP (nasopharyngeal) swabs. Lower Limit of Quantification is 2 (log 10 copies/ml).	Day 14
Primary	Proportion of Participants With New Adverse Event (AE) = Grade 3 (Phase 2)	AE Severity: Adverse event Severity grading followed Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017, which can be found on the DAIDS RSC website at: https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables.; Grade 1 indicates a mild event; Grade 2 indicates a moderate event; Grade 3 indicates a severe event; Grade 4 indicates a potentially life-threatening event; Grade 5 indicates death	Thru Day 28
Primary	Cumulative Incidence of Death Due to Any Cause or Hospitalization Due to Any Cause (Phase 3)	Hospitalization defined as =24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe COVID-19	Thru Day 28
Primary	Proportion of Participants With New Adverse Event (AE) = Grade 3 (Phase 3)	AE Severity: Adverse event Severity grading followed Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017, which can be found on the DAIDS RSC website at: https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables.; Grade 1 indicates a mild event; Grade 2 indicates a moderate event; Grade 3 indicates a severe event; Grade 4 indicates a potentially life-threatening event; Grade 5 indicates death	Thru Day 28
Secondary	COVID-19 Symptom Duration (Phase 3)	Duration defined as the number of days from start of investigational agent to the first of two consecutive days when any symptoms scored as moderate or severe as study entry (pre-treatment) are scored as mild or absent; and any symptoms scored as mild or absent at study entry are scored as absent, AND any symptoms scored as mile or absent at study entry (pre-treatment) are scored as absent. Targeted symptoms are: Feeling feverish; cough, shortness of breath or difficulty breathing; sore throat; body pain or muscle pain/aches; fatigue (low energy); headache, chills, nasal obstruction or congestion (stuffy nose); nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3)	Thru Day 28
Secondary	Quantification of SARS-CoV-2 RNA (Phase 3)	Measured as quantification (	Day 3
Secondary	Cumulative Incidence of Death From Any Cause or Hospitalization Due to Any Cause (Phase 2)	Hospitalization defined as =24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe COVID-19	Thru Day 28
Secondary	Cumulative Incidence of Death From Any Cause, or Hospitalization Due to Any Cause Related to COVID-19 (Phase 3)	Hospitalizations due to any cause deemed unrelated to COVID-19 are excluded. Hospitalization defined as =24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe COVID-19	Thru Day 28
Secondary	Level of SARS-CoV-2 RNA From NP Swabs (Phase 2)	Measured from staff-collected NP swabs	Thru Day 14
Secondary	Level of SARS-CoV-2 RNA From NP Swabs (Phase 3)	Measured from staff-collected NP swabs	Day 3
Secondary	Duration of Targeted Clinical COVID-19 Symptoms (Phases 2 and 3)	Duration defined as the number of days from start of investigational agent to the first of four consecutive days when all symptoms scored as absent. Targeted symptoms are: Feeling feverish; cough, shortness of breath or difficulty breathing; sore throat; body pain or muscle pain/aches; fatigue (low energy); headache, chills, nasal obstruction or congestion (stuffy nose); nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3)	Thru Day 28
Secondary	COVID-19 Symptom Severity Ranking (Phases 2 and 3)	Symptoms scored daily as absent (score 0), mild (score 1), moderate (score 2) or severe (score 3). Symptoms: feeling feverish, cough, shortness of breath/difficulty breathing at rest/with activity, sore throat, body pain/muscle pain/aches, fatigue, headache, chills, nasal obstruction/congestion, nasal discharge, nausea, vomiting, and diarrhea. Subjects alive and never hospitalized through Day 28: Symptom Severity Ranking=subject-specific AUC (area under curve) joining daily total symptom score associated with COVID-19 disease, over time (through Day 28, counting Day 0 as first day), calculated by trapezoidal rule and rescaled for time by dividing by the total number of trapezoids. Subjects who died within Day 28: Assigned severity score 42; Subjects alive but remaining hospitalized at Day 28: Assigned severity score 41; Subjects alive but no longer hospitalized at Day 28: Assigned severity score 40.; Calculated Severity Score=scale of 0 to 42. Higher value=worse health condition.	From Day 0 thru Day 28
Secondary	Proportion of Participants With =1 Worsening Symptom of COVID-19 (Phases 2 and 3)	Progression of one or more COVID-19-associated symptoms to a worse status than recorded in study diary at study entry, prior to start of investigational product or placebo	Thru Day 28
Secondary	Time to Self-reported Return to Usual Health (a) (Phases 2 and 3)	Defined as the number of days from start of investigational treatment until the first of two consecutive days that a participant reported return to usual (pre-COVID-19) health as recorded in a participant's study diary	Thru Day 28
Secondary	Cumulative Incidence of Death Due to Any Cause or Hospitalization Due to Any Cause (Phases 2 and 3)		Day 0 thru Week 24
Secondary	Cumulative Incidence of Death Due to Any Cause or Hospitalization Due to Any Cause (Phases 2 and 3)		Day 0 thru Week 72
Secondary	Oxygen Saturation Level (Phases 2 and 3)	Measured by pulse oximeter and categorized as <96% versus =96%	Thru Day 28
Secondary	AUC of SARS-CoV-2 RNA From Site-collected NP Swabs (Phase 2)	Measured by area under the curve (AUC) and above assay lower limit of quantification of quantitative SARS-CoV-2 RNA over time	Thru Day 14
Secondary	Incidence of New Adverse Event (AE) = Grade 2 (Phases 2 and 3)		Thru Day 28
Secondary	Incidence of New Adverse Event (AE) = Grade 2 (Phases 2 and 3)		Thru Week 24
Secondary	Incidence of New Adverse Event (AE) = Grade 3 (Phases 2 and 3)		Thru Week 24
Secondary	Time to Self-reported Return to Usual Health (b) (Phases 2 and 3)	Defined as the number of days from start of investigational treatment until the first of four consecutive days that a participant reported return to usual (pre-COVID-19) health as recorded in a participant's study diary	Thru Day 28

External Links

•   A Participant's Guide to Clinical Trials (NIAID)
•   CDC (Centers for Disease Control and Prevention): Coronavirus (COVID-19) website
•   Clinical Trials at NIAID
•   FDA Safety Alerts and Recalls
•   Find a Clinical Trial (NIAID)
•   National Institute for Allergy and Infectious Diseases (NIAID)
•   NIH COVID-19 treatment guidelines
•   NIH: Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)
•   WHO COVID-19 treatment guidelines