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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: RO7496998
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RO7496998 (AT-527)<br>Orally administered, 550 mg twice daily (BID) for 5 days | Drug: RO7496998<br>* 275 mg tablets<br>* Other names: AT-527;|
| Placebo Comparator: Placebo<br>The dose and regimen of the placebo will match that of AT-527. | Drug: Placebo<br>* Matching tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Proportion of Participants Requiring Hospitalization for COVID-19 |  | Up to 33 days | 
| 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 | 
| 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 | 
| 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 | 
| Proportion of Participants with any Post-Treatment Infection |  | Up to 33 days | 
| 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 | 
| 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 | 
| Proportion of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints |  | Up to 14 days | 
| 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 | 
| Percentage of Participants with Adverse Events (AEs) |  | Up to 33 days | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus Disease 2019; COVID-19; antiviral drug; SARS-CoV-2; Mild to Moderate COVID-19; antiviral efficacy