Study to Evaluate the Effects of RO7496998 (AT-527) in Non-Hospitalized Adult and Adolescent Participants With Mild or Moderate COVID-19
- Registration Number
- NCT04889040
- Lead Sponsor
- Hoffmann-La Roche
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 216
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo The dose and regimen of the placebo will match that of AT-527. RO7496998 (AT-527) RO7496998 Orally administered, 550 mg twice daily (BID) for 5 days
- Primary Outcome Measures
Name Time Method Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours) Up to 29 days 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).
The time to alleviation or improvement of COVID-19 symptoms is defined as follows: for new symptoms, it 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, it is defined as 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.
- Secondary Outcome Measures
Name Time Method Time to Alleviation of COVID-19 Symptoms (43 Hours) Up to 29 days 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.Time to Cessation of SARS-CoV-2 Viral Shedding Up to 14 days Defined as time from randomization to the first time when a negative qualitative virus RNA by RT-PCR test result is obtained.
Percentage of Participants With Adverse Events (AEs) Up to Day 33 visit Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours) Up to 29 days 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).
The time to alleviation or improvement of COVID-19 symptoms is defined as follows: for new symptoms, it 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, it is defined as 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.Time to Alleviation of Individual Symptoms Up to 29 days 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 DiaryDuration of Fever Up to 29 days Time to return to an afebrile state (temperature ≤ 37.5°C) maintained for at least 21.5 hours.
Percentage of Participants With Any Post-Treatment Infection Up to Day 33 visit Post-treatment infections were defined as any treatment-emergent adverse event with a primary system organ class of infections and infestations.
Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA Baseline and on Days 3, 5, 7 and 14 SARS-CoV-2 virus RNA will be measured by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR)
Plasma Concentration of AT-551 at Specified Timepoints Up to 7 days 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)
Plasma Concentration of AT-273 at Specified Timepoints Up to 7 days 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)
Time to Alleviation of COVID-19 Symptoms (21.5 Hours) Up to 29 days 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.Time to One-Category Improvement of Baseline Presenting COVID-19 Symptoms Up to 29 days Time from randomization to the point at which symptoms (Items 1-12 of the COVID-19 Symptom Diary) have improved by at least one category from baseline on the COVID-19 Symptom Diary Likert scale, maintained for at least 21.5 hours.
Percentage of Participants Requiring Hospitalization for COVID-19 Up to Day 33 visit Hospitalizations for COVID-19 are defined as SAEs for which the investigator has cited that the suspected cause was the disease under study and where there is a non-missing hospital admission date.
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints Baseline and on Days 3, 5, 7 and 14 Defined as percentage of participants with a positive qualitative virus RNA by RT-PCR.
Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA Day 1 prior to dosing, Day 3, Day 5, Day 7 and Day 14 Plasma Concentration of AT-511 at Specified Timepoints Up to 7 days AT-511 is the free base form of RO7496998 (AT-527).
Plasma Concentration of AT-229 at Specified Timepoints Up to 7 days 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)
Percentage of Participants With Greater Than or Equal to 1 COVID-19 Related Medically Attended Visit Up to Day 33 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.
Percentage of Participants With COVID-19 Related Complications Up to Day 33 visit COVID-related complications are defined as death, hospitalization, pneumonia, sepsis, coagulopathy, pericarditis/myocarditis and cardiac failure.
Pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis/myocarditis, and cardiac failure were adjudicated per blinded manual medical review of events by an internal adjudication team before study readout.
Trial Locations
- Locations (50)
Higashiosaka city Medical Center
🇯🇵Higashiosaka-Shi, Japan
County Hospital Caracal
🇷🇴Caracal, Romania
Maison Médicale La Brèche
🇧🇪Châtelineau, Belgium
Medif
🇧🇪Gozée, Belgium
Rinku General Medical Center
🇯🇵Izumisano, Japan
Misyuku hospital
🇯🇵Meguro-Ku, Japan
Houjin Syadan Kouhoukai Takagi Hospital
🇯🇵Okawa-Shi, Japan
Instituto Jalisciense de Investigacion Clinica S.A. de C.V.
🇲🇽Guadalajara, Mexico
Unidade Local de Saude de Matosinhos SA
🇵🇹Matosinhos, Portugal
Ege University Medical Faculty
🇹🇷Izmir, Turkey
Edogawa Medicare Hospital
🇯🇵Tokyo, Japan
CIMAB SA de CV
🇲🇽Torreón, Coahuila, Mexico
CNPE City Clinical Hospital #6 of DCC
🇺🇦Dnipro, Kholm Governorate, Ukraine
Medical Center LLC "Harmony of Beauty"
🇺🇦Kyiv, KIEV Governorate, Ukraine
Center Hospital of the National Center for Global Health and Medicine
🇯🇵Tokyo, Japan
Prof. Dr. Matei Bals Institute of Infectious Diseases
🇷🇴Bucuresti, Romania
Hôpital Universitaire de Genève (HUG)
🇨🇭Genève, Switzerland
Polyclinic of Center of Medical Service and Rehabilitation of State JSHC Artem
🇺🇦Kyiv, KIEV Governorate, Ukraine
PanAmerican Clinical Research, Querétaro
🇲🇽Queréaro, Queretaro, Mexico
Clinstile S.A de C.V.
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
Karadeniz Technical University Faculty of Medicine
🇹🇷Trabzon, Turkey
CNE Kyiv City Clinical Hospital#1 of Exec. Body
🇺🇦Kyiv, KIEV Governorate, Ukraine
Universitätsspital Zürich
🇨🇭Zürich, Switzerland
Kyiv Railway Clinical Hospital No2 of Branch Health Center of the JSC Ukrainian Rail
🇺🇦Kyiv, KIEV Governorate, Ukraine
Communal Non-Profit Enterprise City Hospital #7 of Zaporizhzhia City Council
🇺🇦Zaporizhzhia, Tavria Okruha, Ukraine
Communal Non-Commercial Enterprise Vinnytsia City Clinical Hospital 1
🇺🇦Vinnytsya, Podolia Governorate, Ukraine
Instituto Ave Pulmo
🇦🇷Mar Del Plata, Argentina
IUHW Narita Hospital
🇯🇵Narita, Japan
Chronos Pesquisa Clinica
🇧🇷Taguatinga, DF, Brazil
Private Practice Dr Jean Benoit Martinot
🇧🇪Erpent, Belgium
Ome Municipal General Hospital
🇯🇵Ome-Shi, Japan
Hospital Nossa Senhora das Graças
🇧🇷Curitiba, PR, Brazil
Hospital Agamenon Magalhães
🇧🇷Recife, PE, Brazil
L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar
🇧🇷Brasilia, DF, Brazil
Conjunto Hospitalar do Mandaqui
🇧🇷Sao Paulo, SP, Brazil
Aalborg Universitetshospital
🇩🇰Aalborg, Denmark
Praxis am Ebertplatz
🇩🇪Köln, Germany
Rigshospitalet Copenhagen University Hospital
🇩🇰Copenhagen, Denmark
Sagamihara Kyodo Hospital
🇯🇵Kanagawa, Japan
Okayama City Hospital
🇯🇵Okayama, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
🇯🇵Sakai-shi, Japan
Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai
🇯🇵Shinagawa, Japan
Tokyo Medical University Hachioji Medical Center
🇯🇵Tokyo, Japan
Panamerican Clinical Research S.A de C.V.
🇲🇽Guadalajara, Jalisco, Mexico
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
🇲🇽Mexico, Mexico
Sibiu Emergency Clinical County Hospital
🇷🇴Sibiu, Romania
Gazi Universitesi Tip Fakultesi
🇹🇷Ankara, Turkey
Ankara University Medical Faculty - PPDS
🇹🇷Çankaya, Turkey
Public Non-Profit Enterprise ?City Outpatient Clinic #9? of Kharkiv City Council
🇺🇦Kharkiv, Kharkiv Governorate, Ukraine
Municipal Non-profit Enterprise ?City Clinical Hospital #13? of Kharkiv City Council
🇺🇦Kharkiv, Kharkiv Governorate, Ukraine