LY3819253 (LY-CoV555) for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)

COVID-19 Clinical Trial

Official title:

A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19 (Trial H1: LY3819253 (LY-CoV555))

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05780268
• Other study ID #: 014/ACTIV-3/H1
• Status: Completed
• Phase: Phase 3
• Start date: August 5, 2020
• Est. completion date: February 1, 2021

Study information

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

Clinical Trial Summary

This study looks at the safety and effectiveness of LY3819253 in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either LY3819253 plus current standard of care (SOC), or with placebo plus current SOC. This is ACTIV-3/TICO Treatment Trial H1.

Description:

This is a treatment trial of the ACTIV-3/TICO master protocol (NCT04501978) to evaluate the safety and efficacy of LY3819253 in hospitalized patients infected with COVID-19.

This is a randomized, blinded, controlled sub-study of LY3819253 plus current standard of care (SOC) against placebo plus current SOC. The placebo arm may be shared across other sub-studies of the ACTIV-3/TICO master protocol. When more than one drug is being tested at the same time, participants will be randomly allocated to treatments or placebo.

Randomization will be stratified by study site pharmacy and disease severity. There are 2 disease severity strata: Participants without organ failure (severity stratum 1) and participants with organ failure (severity stratum 2).

An independent Data and Safety Monitoring Board (DSMB) will regularly review interim analyses and summarize safety and efficacy outcomes. The pace of enrollment with be initially restricted, and there will be an early review of safety data by the DSMB. At the outset of the trial, only participants in disease severity stratum 1 will be enrolled. This will continue until approximately 300 participants are enrolled and followed for 5 days. The exact number will vary according to the speed of enrollment and the timing of DSMB meetings. Prior to expanding enrollment to also include patients in disease severity stratum 2, safety will be evaluated and a pre-specified futility assessment by the DSMB will be carried out using 2 ordinal outcomes assessed at Day 5.

If LY3819253 passes the futility assessment, enrollment of participants will be expanded, seamlessly and without any data unblinding, to include participants in disease severity stratum 2 as well as those in disease severity stratum 1. Future interim analyses will be based on the primary endpoint of sustained recovery and will use pre-specified guidelines to determine early evidence of benefit, harm, or futility for the investigational agent. Participants will be followed for 18 months following randomization.

This trial will be conducted in several hundred clinical sites. Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 314
• Est. completion date: February 1, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: Refer to the master protocol (NCT04501978)

Exclusion Criteria: Refer to the master protocol (NCT04501978)

Additional Criteria:

Non-pregnant female participants who are of reproductive potential and male participants who are able to father a child must abstain from male/female sexual intercourse or agree to use two forms of effective contraception, where at least one form is highly effective (less than 1% failure rate), for the entirety of the study and for 90 days after investigational agent is administered. Highly effective methods of contraception (less than 1% failure rate) include, but are not limited to:

• combination oral contraceptives

• implanted contraceptives

• intrauterine devices

Effective methods of contraception include, but are not limited to:

• diaphragms and cervical caps with spermicide

• cervical sponges

• condoms with spermicide

NOTE:

• Use of male and female condoms as a double barrier method is not considered acceptable due to the high failure rate when these barrier methods are combined.

• Barrier protection methods without concomitant use of a spermicide are not an effective or acceptable method of contraception.

• Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), and withdrawal are not acceptable methods of contraception. Participants not of reproductive potential are eligible without requiring the use of a contraceptive method. Participant-reported history is acceptable documentation of surgical sterilization and menopause. Participants with pregnant partners should use condoms during vaginal intercourse through 90 days after investigational agent administration. Participants should refrain from sperm donation through 90 days after investigational agent administration. NOTE: Reproductive potential is defined as patients who have reached menarche, who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) = 40 IU/ml or 24 consecutive months if an FSH is not available, who have not undergone surgical sterilization, who do not have other clinical condition that could induce amenorrhea, who are not taking medications such as oral contraceptives, hormones, gonadotropin releasing hormone, antiestrogens, selective estrogen receptor modulators (SERMs) or chemotherapy that could induce amenorrhea. Individuals with permanent infertility due to an alternate medical cause (e.g. Mullerian agenesis, androgen insensitivity), investigator discretion should be applied.

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• LY3819253
LY3819253 is a neutralizing immunoglobulin G (IgG)-1 monoclonal antibody (mAb) to the receptor binding domain (RBD) of the S protein of SARS-CoV-2
• Placebo
Commercially available 0.9% sodium chloride solution
• Remdesivir
Antiviral agent

Locations

Country	Name	City	State
Denmark	Aalborg Hospital (Site 625-005), Hobrovej 18	Aalborg
Denmark	Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99	Aarhus N
Denmark	Righospitalet (Site 625-006), Blegdamsvej 9,	Copenhagen Ø
Denmark	Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75	Herlev
Denmark	Nordsjællands Hospital (Site 625-009), Dyrehavevej 29	Hillerød
Denmark	Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30	Hvidovre
Denmark	Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24	Kolding
Denmark	Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4	Odense
Singapore	Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng	Singapore
Spain	Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n	Badalona	Barcelona
Spain	Hospital Clínic de Barcelona (Site 626-004), Carrer de Villaroel 170	Barcelona
Spain	Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29	Barcelona
Spain	Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN	Madrid
Spain	Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46	Madrid
Spain	UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal	Madrid
United States	University of Michigan (Site 205-001), 1500 East Medical Center Drive	Ann Arbor	Michigan
United States	Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE	Atlanta	Georgia
United States	University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue	Aurora	Colorado
United States	University of Maryland Medical Center (Site 301-019), 22 South Greene Street	Baltimore	Maryland
United States	Massachusetts General Hospital (Site 202-002), 55 Fruit Street	Boston	Massachusetts
United States	Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street	Bronx	New York
United States	Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road	Bronx	New York
United States	University of Virginia Health Systems (Site 301-021), 1215 Lee Street	Charlottesville	Virginia
United States	Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue	Cleveland	Ohio
United States	Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue	Cleveland	Ohio
United States	Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.	Dallas	Texas
United States	UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor	Dallas	Texas
United States	Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic)	Denver	Colorado
United States	Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.	Detroit	Michigan
United States	Duke University Hospital (Site 301-006), 2301 Erwin Road	Durham	North Carolina
United States	Community Regional Medical Center (Site 203-005), 2823 Fresno Street	Fresno	California
United States	Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road	Garfield Heights	Ohio
United States	Memorial Hermann Hospital (Site 203-006), 6411 Fannin Street	Houston	Texas
United States	Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.	Houston	Texas
United States	University of Mississippi Medical Center (Site 202-005), 2500 North State Street	Jackson	Mississippi
United States	Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive	Lebanon	New Hampshire
United States	University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.	Lexington	Kentucky
United States	Keck Hospital of USC (Site 301-020), 1500 San Pablo Street	Los Angeles	California
United States	Miami VAMC (Site 074-003), 1201 NW 16 Street	Miami	Florida
United States	Hennepin Healthcare (Site 027-001), 701 Park Avenue	Minneapolis	Minnesota
United States	West Virginia University (Site 301-023), One Medical Center Drive	Morgantown	West Virginia
United States	Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street	Murray	Utah
United States	Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive	Nashville	Tennessee
United States	Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway	New Orleans	Louisiana
United States	Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.	Portland	Oregon
United States	Virginia Commonwealth University Health System (Site 210-005), 1250 East Marshall Street	Richmond	Virginia
United States	University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207	Salt Lake City	Utah
United States	San Francisco VAMC (Site 074-002), 4150 Clement St.	San Francisco	California
United States	UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave.	San Francisco	California
United States	UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.	San Francisco	California
United States	Harborview Medical Center (Site 208-001), 325 9th Avenue	Seattle	Washington
United States	University of Washington Medical Center - Montlake (Site 208-006), 1959 NE Pacific Street	Seattle	Washington
United States	Baystate Medical Center (Site 201-001), 759 Chestnut Street	Springfield	Massachusetts
United States	Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.	Stanford	California
United States	Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue	Tucson	Arizona
United States	MedStar Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW	Washington	District of Columbia
United States	Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd	Winston-Salem	North Carolina

Sponsors (13)

Lead Sponsor

Collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

AIDS Clinical Trials Group, Cardiothoracic Surgical Trials Network, Eli Lilly and Company, International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), Kirby Institute, Medical Research Council, National Heart, Lung, and Blood Institute (NHLBI), Prevention and Early Treatment of Acute Lung Injury, University of Copenhagen, University of Minnesota, US Department of Veterans Affairs, Washington D.C. Veterans Affairs Medical Center

Countries where clinical trial is conducted

United States,  Denmark,  Singapore,  Spain, 

References & Publications (1)

ACTIV-3/TICO LY-CoV555 Study Group; Lundgren JD, Grund B, Barkauskas CE, Holland TL, Gottlieb RL, Sandkovsky U, Brown SM, Knowlton KU, Self WH, Files DC, Jain MK, Benfield T, Bowdish ME, Leshnower BG, Baker JV, Jensen JU, Gardner EM, Ginde AA, Harris ES, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Sustained Recovery	Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.	Through Day 90
Primary	Number of Participants With an Ordinal Outcome on Day 5	Ordinal outcome with 7 mutually exclusive categories	Status on Day 5
Secondary	Number of Participants Who Died From All Causes	All-cause mortality	Through Day 90
Secondary	Number of Participants With a Safety Outcome Through Day 5	Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 5	Through Day 5
Secondary	Number of Participants With a Safety Outcome Through Day 28	Death, SAE, clinical organ failure, serious infections, or Grade 3 or 4 event through Day 28	Through Day 28
Secondary	Number of Participants With a Safety Outcome Through Day 90	Death, SAE, clinical organ failure, serious infections through Day 90	Through Day 90