SUNRISE-3: Efficacy and Safety of Bemnifosbuvir in High-Risk Outpatients With COVID-19

Study Overview
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Brief Summary
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The purpose of the study is to evaluate whether bemnifosbuvir (BEM) is effective and safe in adults with COVID-19 who do not need to be in the hospital but who are at high risk for progression to severe disease. Eligible subjects will be randomly assigned (by chance) to receive BEM or matching placebo orally for 5 days. Co-administration of locally available standard of care (SOC) is allowed. The total duration of the study is 60 days.

Official Title
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A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Bemnifosbuvir in High-Risk Outpatients With COVID-19

Conditions
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SARS CoV 2 Infection, COVID-19

Intervention / Treatment
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* Drug: Bemnifosbuvir (BEM)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive SARS-CoV-2 test conducted ≤ 5 days prior to randomization Mild or moderate COVID-19 with symptom onset ≤ 5 days before randomization and at least one COVID-19 related symptom present at time of screening Subject must be high risk, defined below: Age ≥70 years OR Age ≥55 years with one of the following: i) obesity (body mass index [BMI] ≥30 kg/m2) ii) diabetes mellitus iii) cardiovascular disease or hypertension iv) chronic lung disease requiring routine therapy OR Age 50 to 54 years with two of the following: i) obesity (BMI ≥30 kg/m2) ii) diabetes mellitus iii) cardiovascular disease or hypertension iv) chronic lung disease requiring routine therapy OR Age ≥18 years with one of the following: i) Down syndrome, sickle cell disease, dementia, Parkinson's disease, or care home residents ii) One of the following immunocompromising conditions or immunosuppressive treatments: receiving chemotherapy for cancer, hematologic malignancy, being within 2 years of a hematopoietic stem cell transplant, receipt of a solid organ transplant and on immunosuppressive therapy, human immunodeficiency virus (HIV) infection untreated or with CD4+ T lymphocyte count <350 cells per cubic millimeter, moderate/severe primary immunodeficiency, taking immunosuppressive medications Use of adequate contraception for females of childbearing potential Exclusion Criteria: Severe or critical COVID-19 illness Admitted to a hospital within 90 days prior to randomization due to COVID-19 Use of other investigational drugs within 30 days prior to planned dosing, or plans to enroll in another clinical trial of an investigational agent while participating in the present study Initiation or planned initiation of remdesivir for treatment of the current SARS-CoV-2 infection Requirement of prohibited medications, including hydroxychloroquine or amiodarone within 3 months prior to screening. Note: Subjects who had already initiated any COVID-19 drug with antiviral effects intended to treat symptomatic SARS-CoV-2 infection (≥ 24 hours prior to randomization) will be excluded. During screening (or within 24 hours prior to or after randomization), locally available COVID-19 drugs with antiviral effects (including but not limited to nirmatrelvir/ritonavir, molnupiravir, favipiravir, monoclonal antibodies) will be permitted. Other known active viral or bacterial infection at the time of screening, such as influenza and respiratory syncytial virus (RSV). Note: This exclusion does not apply to subjects with stable chronic viral infections, such as chronic hepatitis C virus (HCV) or HIV providing other eligibility criteria are met. Receiving dialysis or have known severe renal impairment History of severe hepatic impairment (Child-Pugh Class C) Known allergy or hypersensitivity to components of study drug

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bemnifosbuvir (BEM)<br> | Drug: Bemnifosbuvir (BEM)<br>* BEM tablets administered orally every 12 hours (twice a day) for a total of 5 days<br>* Other names: AT-527;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo tablets administered orally every 12 hours (twice a day) for a total of 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects hospitalized for any cause or died due to any cause |  | Day 1 through Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects hospitalized due to COVID-19 or died due to any cause |  | Day 1 through Day 29 | 
| Proportion of subjects who died due to any cause |  | Day 1 through Day 29; Day 1 through Day 60 | 
| Proportion of subjects with COVID-19-related complications |  | Day 1 through Day 29 | 
| Proportion of subjects with COVID-19-medically attended visits (hospitalization, emergency room (ER) visit, urgent care visit, physician's office visit, or telemedicine visit) or who died due to any cause |  | Day 1 through Day 29; Day 1 through Day 60 | 
| Proportion of subjects with COVID-19 symptom relapse |  | Day 1 through Day 29 | 
| Proportion of subjects with viral load rebound |  | Day 1 through Day 29 |