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

Hoffmann-La Roche50 sites in 12 countries216 target enrollmentApril 28, 2021

ConditionsCOVID-19

InterventionsPlacebo RO7496998

Overview

Phase: Phase 3
Intervention: Placebo
Conditions: COVID-19
Sponsor: Hoffmann-La Roche
Enrollment: 216
Locations: 50
Primary Endpoint: Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours)
Status: Terminated
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

April 28, 2021

End Date

December 2, 2021

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

Placebo

The dose and regimen of the placebo will match that of AT-527.

Intervention: Placebo

RO7496998 (AT-527)

Orally administered, 550 mg twice daily (BID) for 5 days

Intervention: RO7496998

Outcomes

Primary Outcomes

Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours)

Time Frame: 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 Outcomes

Time to Alleviation of COVID-19 Symptoms (43 Hours)(Up to 29 days)
Time to Cessation of SARS-CoV-2 Viral Shedding(Up to 14 days)
Percentage of Participants With Adverse Events (AEs)(Up to Day 33 visit)
Time to One-Category Improvement of Baseline Presenting COVID-19 Symptoms(Up to 29 days)
Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours)(Up to 29 days)
Time to Alleviation of Individual Symptoms(Up to 29 days)
Duration of Fever(Up to 29 days)
Percentage of Participants With Any Post-Treatment Infection(Up to Day 33 visit)
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)
Plasma Concentration of AT-551 at Specified Timepoints(Up to 7 days)
Plasma Concentration of AT-273 at Specified Timepoints(Up to 7 days)
Time to Alleviation of COVID-19 Symptoms (21.5 Hours)(Up to 29 days)
Percentage of Participants Requiring Hospitalization for COVID-19(Up to Day 33 visit)
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints(Baseline and on Days 3, 5, 7 and 14)
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)
Plasma Concentration of AT-229 at Specified Timepoints(Up to 7 days)
Percentage of Participants With Greater Than or Equal to 1 COVID-19 Related Medically Attended Visit(Up to Day 33 visit)
Percentage of Participants With COVID-19 Related Complications(Up to Day 33 visit)