Study to Evaluate the Effects of RO7496998 (AT-527) in Non-Hospitalized Adult and Adolescent Participants With Mild or Moderate COVID-19

COVID-19 Clinical Trial

— MORNINGSKY  

Official title:

A Multicenter, Phase III Randomized, Double-Blind, Placebo-Controlled, Outpatient Study to Evaluate the Efficacy, Safety, Antiviral Activity of RO7496998 (AT-527) in Patients With Mild or Moderate COVID-19

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05126576
• Other study ID #: CV43043
• Secondary ID: 2020-005759-18
• Status: Suspended
• Phase: Phase 3
• Start date: April 28, 2021
• Est. completion date: November 17, 2021

Study information

• Verified date: November 2021
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy, safety, antiviral activity, and pharmacokinetics of study drug RO7496998 (AT-527) compared to placebo in non-hospitalized adult and adolescent participants with mild to moderate coronavirus disease 2019 (COVID-19) in the outpatient setting.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 1386
• Est. completion date: November 17, 2021
• Est. primary completion date: November 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Positive SARS-CoV-2 diagnostic test (RT-PCR or validated rapid antigen test) =72 hours prior to randomization

• At least three of the following symptoms of at least moderate (score =2 as per COVID-19 Symptom Diary) intensity: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills or sweats, feeling hot or feverish, nausea, vomiting, or diarrhea.

• Has symptoms consistent with mild or moderate COVID-19, as determined by the investigator, with onset =5 days before dosing on Day 1

Exclusion Criteria:

• Clinical signs indicative of COVID-19 illness requiring hospitalization

• Admitted to a hospital prior to randomization or is hospitalized (inpatient) at randomization due to COVID-19

• In the opinion of the investigator, is likely to experience imminent deterioration and require hospitalization

• Treatment with an investigational drug within 5 half-lives or 3 months (whichever is longer) of randomization

• Treatment with a COVID-19 therapeutic agent including, but not limited to, other direct or indirect acting antivirals against SARS-CoV-2 (such as remdesivir or favipiravir), systemic or inhaled steroids (such as dexamethasone or inhaled budesonide), colchicine, ivermectin, interferons, convalescent plasma, monoclonal antibodies against SARS CoV-2 or interleukin 6 (IL-6), intravenous immunoglobulin or other EUA-approved treatments within 3 months or less than 5 drug elimination half-lives (whichever is longer) prior to the screening visit

• Concomitant use of P-glycoprotein inhibitors or inducers listed as prohibited therapy in the protocol

• Known allergy or hypersensitivity to components of study drug

• Abnormal laboratory test results at screening

• Requirement of any prohibited medications during the study

• Other known active viral or bacterial infection at the time of screening, such as influenza

• Any clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, could jeopardize the safety of the patient or affect patient compliance or safety/efficacy observations during the study

• COVID-19 vaccination within = 40-days prior to enrollment (second dose if applicable)

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• RO7496998
275 mg tablets
• Placebo
Matching tablets

Locations

Country	Name	City	State
Argentina	Instituto Medico Rio Cuarto	Cordoba
Argentina	Instituto Ave Pulmo	Mar Del Plata
Argentina	Clínica Independencia	Munro
Argentina	Instituto Medico de la Fundacion Estudios Clinicos	Rosario
Argentina	Clinica Mayo de U.M.C.B. S.R.L	San Miguel de Tucumán
Argentina	Sanatorio Medico de Diagnostico Y Tratamiento	Santa Fe
Belgium	Maison Médicale La Brèche	Châtelineau
Belgium	Private Practice Dr Jean Benoit Martinot	Erpent
Belgium	Medif	Gozée
Brazil	Hospital das Clinicas - UFMG	Belo Horizonte	MG
Brazil	L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar	Brasilia	DF
Brazil	Hospital E Maternidade Celso Pierro PUCCAMP	Campinas	SP
Brazil	Hospital Erasto Gaertner	Curitiba	PR
Brazil	Hospital Nossa Senhora das Graças	Curitiba	PR
Brazil	Hospital Agamenon Magalhães	Recife	PE
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS	Sao Jose Do Rio Preto	SP
Brazil	Conjunto Hospitalar do Mandaqui	Sao Paulo	SP
Brazil	CPQuali Pesquisa Clínica Sao Paulo	Sao Paulo	SP
Brazil	Institute of Infectious Diseases Emilio Ribas	Sao Paulo	SP
Brazil	Chronos Pesquisa Clinica	Taguatinga	DF
Denmark	Aalborg Universitetshospital	Aalborg
Denmark	Rigshospitalet Copenhagen University Hospital	Copenhagen
Denmark	Sjællands Universitetshospital, Roskilde	Roskilde
France	Centre Hospitalier Victor Dupouy	Argenteuil
France	Hôpital Saint Joseph	Marseille
France	Hopital Tenon	Paris
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Praxis am Ebertplatz	Köln
Italy	ASST di Lecco - Presidio Ospedaliero A. Manzoni di Lecco	Lecco	Lombardia
Italy	Ospedale San Raffaele S.r.l.	Milano	Lombardia
Italy	Comprensorio Amedeo Di Savoia Birago Di Vische	Torino	Piemonte
Japan	Funabashi Central Hospital	Funabashi-Shi
Japan	Higashiosaka city Medical Center	Higashiosaka-Shi
Japan	Rinku General Medical Center	Izumisano
Japan	Sagamihara Kyodo Hospital	Kanagawa
Japan	Misyuku hospital	Meguro-Ku
Japan	Fujita Health University Banbuntane Hotokukai Hospital	Nagoya-shi
Japan	Nagoya City East Medical Center	Nagoya-Shi Chikusa-Ku
Japan	Tokyo Metropolitan Police Hospital	Nakano-Ku
Japan	IUHW Narita Hospital	Narita
Japan	Houjin Syadan Kouhoukai Takagi Hospital	Okawa-Shi
Japan	Okayama City Hospital	Okayama
Japan	Ome Municipal General Hospital	Ome-Shi
Japan	Osaka City General Hospital	Osaka
Japan	National Hospital Organization Kinki-Chuo Chest Medical Center	Sakai-shi
Japan	Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai	Shinagawa
Japan	Center Hospital of the National Center for Global Health and Medicine	Tokyo
Japan	Edogawa Medicare Hospital	Tokyo
Japan	JCHO Tokyo Shinjuku Medical Center	Tokyo
Japan	St. Luke's International Hospital	Tokyo
Japan	Tokyo Medical University Hachioji Medical Center	Tokyo
Japan	National Hospital Organization Kasumigaura Medical Center	Tsuchiurat
Japan	Mie Prefectural Medical Centre	Yokkaichi
Mexico	Instituto Jalisciense de Investigacion Clinica S.A. de C.V.	Guadalajara
Mexico	Panamerican Clinical Research S.A de C.V.	Guadalajara	Jalisco
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico
Mexico	Clinstile S.A de C.V.	Mexico City	Mexico CITY (federal District)
Mexico	CEPREP; Hospital Universitario	Monterrey
Mexico	PanAmerican Clinical Research, Querétaro	Queréaro	Queretaro
Mexico	CIMAB SA de CV	Torreón	Coahuila
Portugal	Hospital Senhora da Oliveira - Guimaraes, E.P.E	Guimarães
Portugal	Centro Hospitalar de Leiria (CHL)	Leiria
Portugal	Unidade Local de Saude de Matosinhos SA	Matosinhos
Romania	Prof. Dr. Matei Bals Institute of Infectious Diseases	Bucuresti
Romania	County Hospital Caracal	Caracal
Romania	Sibiu Emergency Clinical County Hospital	Sibiu
Romania	Dr. Victor Babes Clinical Hospital of Pneumophthisiology and Infectious Diseases	Timisoara
South Africa	Dr JM Engelbrecht Trial site	Cape Town
South Africa	TASK Eden	George
South Africa	Langeberg Clinical Trials	Kraaifontein
South Africa	Clinical Projects Research	Worcester
Switzerland	Hôpital Universitaire de Genève (HUG)	Genève
Switzerland	Universitätsspital Zürich	Zürich
Turkey	Gazi Universitesi Tip Fakultesi	Ankara
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Ankara University Medical Faculty - PPDS	Çankaya
Turkey	Koc University Medical Faculty Hospital	Istanbul
Turkey	Ege University Medical Faculty	Izmir
Turkey	Istanbul University Cerrahpasa Medical Faculty Hospital; Tesvikiye Caddesi No:20	Si?sli?
Turkey	Karadeniz Technical University Faculty of Medicine	Trabzon
Ukraine	CNPE City Clinical Hospital #6 of DCC	Dnipro	Kholm Governorate
Ukraine	Municipal Non-profit Enterprise "City Clinical Hospital # 4" of Dnipro City Council	Dnipro	KIEV Governorate
Ukraine	CNPE Ivano-Frankivsk Regional Centre of Phthisiology and Pulmonology of IFRC	Ivano Frankivsk	KIEV Governorate
Ukraine	Municipal Non-profit enterprise Central City Clinical Hospital of Ivano-Frankivsk City Council	Ivano-Frankivsk	Katerynoslav Governorate
Ukraine	Municipal Non-profit Enterprise "City Clinical Hospital #13" of Kharkiv City Council	Kharkiv	Kharkiv Governorate
Ukraine	Public Non-Profit Enterprise "City Outpatient Clinic #9" of Kharkiv City Council	Kharkiv	Kharkiv Governorate
Ukraine	Private Enterprise Private Manufacture Company "Acinus", diagnostic and treatment center	Kirovograd	KIEV Governorate
Ukraine	CNE Kyiv City Clinical Hospital#1 of Exec. Body	Kyiv	KIEV Governorate
Ukraine	Kyiv Railway Clinical Hospital No2 of Branch Health Center of the JSC Ukrainian Rail	Kyiv	KIEV Governorate
Ukraine	Medical Center LLC "Harmony of Beauty"	Kyiv	KIEV Governorate
Ukraine	Medical Center of LLC Preventclinic	Kyiv	KIEV Governorate
Ukraine	Polyclinic of Center of Medical Service and Rehabilitation of State JSHC Artem	Kyiv	KIEV Governorate
Ukraine	Communal Non-Commercial Enterprise Vinnytsia City Clinical Hospital 1	Vinnytsya	Podolia Governorate
Ukraine	Communal Non-Profit Enterprise City Hospital #7 of Zaporizhzhia City Council	Zaporizhzhia	Tavria Okruha

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Argentina,  Belgium,  Brazil,  Denmark,  France,  Germany,  Italy,  Japan,  Mexico,  Portugal,  Romania,  South Africa,  Switzerland,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 hours)	COVID-19 symptoms will be evaluated using the COVID-19 Symptom Diary (questions 1-12). The severity of each COVID-19 symptom will be recorded on a Likert scale (i.e none/mild/moderate/severe).; Alleviation of new symptoms is defined as the length of time taken from randomization to the point at which a Score of 0 or 1 has been maintained for a duration of at least 21.5 hours. For preexisting symptoms, the time from randomization to when a patient's symptoms have been maintained or improved (requires at least a single category improvement from baseline on the COVID-19 Symptom Diary Likert scale) for a duration of 21.5 hours.	Up to 29 days
Secondary	Time to Alleviation or Improvement of COVID-19 Symptoms (43 hours)	COVID-19 symptoms will be evaluated using the COVID-19 Symptom Diary (questions 1-12). The severity of each COVID-19 symptom will be recorded on a Likert scale (i.e none/mild/moderate/severe).; Alleviation of new symptoms is defined as the length of time taken from randomization to the point at which a Score of 0 or 1 has been maintained for a duration of at least 43 hours. For preexisting symptoms, the time from randomization to when a patient's symptoms have been maintained or improved (requires at least a single category improvement from baseline on the COVID-19 Symptom Diary Likert scale) for a duration of 43 hours.	Up to 29 days
Secondary	Time to Alleviation of COVID-19 Symptoms (21.5 hours)	Time from randomization to the point at which the following criterion is met and maintained for at least 21.5 hours.; - Score of 0 or 1 on Items 1-12 of the COVID-19 Symptom Diary.	Up to 29 days
Secondary	Time to Alleviation of COVID-19 Symptoms (43 hours)	Time from randomization to the point at which the following criterion is met and maintained for at least 43 hours.; - Score of 0 or 1 on Items 1-12 of the COVID-19 Symptom Diary.	Up to 29 days
Secondary	Time to One-Category Improvement of Baseline Presenting COVID-19 Symptoms	Time from randomization to the point at which symptoms have improved by at least one category from baseline on the COVID-19 Symptom Diary Likert scale, maintained for at least 21.5 hours.	Up to 29 days
Secondary	Time to Alleviation of Individual Symptoms	Time from randomization to the point at which the following criterion is met and maintained (for each individual symptom) for at least 21.5 hours.; - Score of 0 or 1 for Items 1-14 of the COVID-19 Symptom Diary	Up to 29 days
Secondary	Proportion of Participants Requiring Hospitalization for COVID-19		Up to 33 days
Secondary	Proportion of Participants with Greater than or Equal to 1 COVID-19 Related Medically Attended Visit	Medically attended visit is defined as hospitalization, emergency room (ER) visit, urgent care visit, physician's office visit, or telemedicine visit, with the primary reason for the visit being COVID-19.	Up to 33 days
Secondary	Duration of Fever	Time to return to an afebrile state (temperature = 37.5°C) maintained for at least 21.5 hours	Up to 29 days
Secondary	Frequency of COVID-19 Related Complications	Examples of COVID-19 related complications include death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis/myocarditis and cardiac failure.	Up to 33 days
Secondary	Proportion of Participants with any Post-Treatment Infection		Up to 33 days
Secondary	Change from Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA	SARS-CoV-2 virus RNA will be measured by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR)	Up to 14 days
Secondary	Time to Cessation of SARS-CoV-2 Viral Shedding	Defined as the length of time from randomization to first time when the virus RNA by RT-qPCR is below the limit of detection.	Up to 14 days
Secondary	Proportion of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints		Up to 14 days
Secondary	Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA	AUC in the amount of SARS-CoV-2 virus RNA from randomization to the last sample timepoint.	Up to 14 days
Secondary	Percentage of Participants with Adverse Events (AEs)		Up to 33 days
Secondary	Plasma Concentration of AT-511, AT-551, AT-229 and AT-273 at Specified Timepoints	AT-511 is the free base form of RO7496998 (AT-527). Major metabolites are AT-551, AT-229, and AT-273 (a surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010)	Up to 7 days