COVID-19, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV 2 Infection)
Conditions
Brief summary
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.
Interventions
BEM tablets administered orally every 12 hours (twice a day) for a total of 5 days
DRUGPlacebo
Placebo tablets administered orally every 12 hours (twice a day) for a total of 5 days
Sponsors
Atea Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. Age ≥70 years OR 2. 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 3. 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 4. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Subjects Hospitalized for Any Cause or Died Due to Any Cause | Day 1 through Day 29 |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Subjects Who Died Due to Any Cause | Day 1 through Day 29; Day 1 through Day 60 |
| Percentage of Subjects With COVID-19-related Complications | Day 1 through Day 29 |
| Percentage of Subjects Hospitalized Due to COVID-19 or Died Due to Any Cause | Day 1 through Day 29 |
| Percentage of Subjects With COVID-19 Symptom Relapse | Day 1 through Day 29 |
| Percentage of Subjects With Viral Load Rebound | Day 1 through Day 29 |
| Percentage 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 |
Countries
Argentina, Brazil, Canada, Germany, India, Japan, Latvia, Mexico, Netherlands, Pakistan, Philippines, Romania, South Africa, Spain, Sweden, Tunisia, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BEM - SCO Stratum Supportive Care Only (SCO) Stratum are subjects who did not receive any treatment with direct SARS-CoV-2 antiviral activity in parallel with study drug (BEM or placebo (PBO)). | 1,022 |
| PBO - SCO Stratum Supportive Care Only (SCO) Stratum are subjects who did not receive any treatment with direct SARS-CoV-2 antiviral activity in parallel with study drug (BEM or placebo (PBO)). | 1,033 |
| BEM - Combo Stratum Combination (Combo) Stratum are subjects who did receive treatment with direct SARS-CoV-2 antiviral activity in parallel with study drug (BEM or placebo (PBO)). | 36 |
| PBO - Combo Stratum Combination (Combo) Stratum are subjects who did receive treatment with direct SARS-CoV-2 antiviral activity in parallel with study drug (BEM or placebo (PBO)). | 34 |
| Total | 2,125 |
Baseline characteristics
| Characteristic | BEM - SCO Stratum | PBO - SCO Stratum | BEM - Combo Stratum | PBO - Combo Stratum | Total |
|---|---|---|---|---|---|
| Age, Customized 18-49 years | 28 Participants | 30 Participants | 1 Participants | 2 Participants | 61 Participants |
| Age, Customized 50-64 years | 429 Participants | 432 Participants | 13 Participants | 13 Participants | 887 Participants |
| Age, Customized 65-79 years | 486 Participants | 487 Participants | 18 Participants | 17 Participants | 1008 Participants |
| Age, Customized >= 80 years | 79 Participants | 84 Participants | 4 Participants | 2 Participants | 169 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 861 Participants | 875 Participants | 16 Participants | 18 Participants | 1770 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 123 Participants | 131 Participants | 19 Participants | 16 Participants | 289 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 38 Participants | 27 Participants | 1 Participants | 0 Participants | 66 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 11 Participants | 1 Participants | 0 Participants | 20 Participants |
| Race (NIH/OMB) Asian | 68 Participants | 55 Participants | 3 Participants | 1 Participants | 127 Participants |
| Race (NIH/OMB) Black or African American | 73 Participants | 73 Participants | 3 Participants | 2 Participants | 151 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 4 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 8 Participants | 5 Participants | 3 Participants | 21 Participants |
| Race (NIH/OMB) White | 867 Participants | 882 Participants | 24 Participants | 28 Participants | 1801 Participants |
| Sex: Female, Male Female | 613 Participants | 634 Participants | 18 Participants | 22 Participants | 1287 Participants |
| Sex: Female, Male Male | 409 Participants | 399 Participants | 18 Participants | 12 Participants | 838 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 1,093 | 1 / 1,103 | 0 / 37 | 0 / 36 |
| other Total, other adverse events | 39 / 1,093 | 35 / 1,103 | 6 / 37 | 9 / 36 |
| serious Total, serious adverse events | 9 / 1,093 | 2 / 1,103 | 0 / 37 | 0 / 36 |
Outcome results
Primary
Percentage of Subjects Hospitalized for Any Cause or Died Due to Any Cause
Time frame: Day 1 through Day 29
Population: Modified intent-to-treat (mITT) population included subjects who received \>= 1 dose of study drug and had \>= 1 positive SARS-CoV-2 result through Day 5.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BEM - SCO Stratum | Percentage of Subjects Hospitalized for Any Cause or Died Due to Any Cause | 7 Participants |
| PBO - SCO Stratum | Percentage of Subjects Hospitalized for Any Cause or Died Due to Any Cause | 2 Participants |
| BEM - Combo Stratum | Percentage of Subjects Hospitalized for Any Cause or Died Due to Any Cause | 0 Participants |
| PBO - Combo Stratum | Percentage of Subjects Hospitalized for Any Cause or Died Due to Any Cause | 0 Participants |
p-value: 0.954Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects Hospitalized Due to COVID-19 or Died Due to Any Cause
Time frame: Day 1 through Day 29
Population: Modified intent-to-treat (mITT) population included subjects who received \>= 1 dose of study drug and had \>= 1 positive SARS-CoV-2 result through Day 5.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BEM - SCO Stratum | Percentage of Subjects Hospitalized Due to COVID-19 or Died Due to Any Cause | 4 Participants |
| PBO - SCO Stratum | Percentage of Subjects Hospitalized Due to COVID-19 or Died Due to Any Cause | 2 Participants |
| BEM - Combo Stratum | Percentage of Subjects Hospitalized Due to COVID-19 or Died Due to Any Cause | 0 Participants |
| PBO - Combo Stratum | Percentage of Subjects Hospitalized Due to COVID-19 or Died Due to Any Cause | 0 Participants |
Secondary
Percentage of Subjects Who Died Due to Any Cause
Time frame: Day 1 through Day 29; Day 1 through Day 60
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BEM - SCO Stratum | Percentage of Subjects Who Died Due to Any Cause | Through Day 29 | 2 Participants |
| BEM - SCO Stratum | Percentage of Subjects Who Died Due to Any Cause | Through Day 60 | 3 Participants |
| PBO - SCO Stratum | Percentage of Subjects Who Died Due to Any Cause | Through Day 60 | 1 Participants |
| PBO - SCO Stratum | Percentage of Subjects Who Died Due to Any Cause | Through Day 29 | 1 Participants |
| BEM - Combo Stratum | Percentage of Subjects Who Died Due to Any Cause | Through Day 29 | 0 Participants |
| BEM - Combo Stratum | Percentage of Subjects Who Died Due to Any Cause | Through Day 60 | 0 Participants |
| PBO - Combo Stratum | Percentage of Subjects Who Died Due to Any Cause | Through Day 29 | 0 Participants |
| PBO - Combo Stratum | Percentage of Subjects Who Died Due to Any Cause | Through Day 60 | 0 Participants |
Secondary
Percentage 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
Time frame: Day 1 through Day 29; Day 1 through Day 60
Population: Modified intent-to-treat (mITT) population included subjects who received \>= 1 dose of study drug and had \>= 1 positive SARS-CoV-2 result through Day 5.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BEM - SCO Stratum | Percentage 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 | Through Day 29 | 7 Participants |
| BEM - SCO Stratum | Percentage 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 | Through Day 60 | 8 Participants |
| PBO - SCO Stratum | Percentage 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 | Through Day 60 | 12 Participants |
| PBO - SCO Stratum | Percentage 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 | Through Day 29 | 11 Participants |
| BEM - Combo Stratum | Percentage 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 | Through Day 29 | 1 Participants |
| BEM - Combo Stratum | Percentage 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 | Through Day 60 | 1 Participants |
| PBO - Combo Stratum | Percentage 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 | Through Day 29 | 0 Participants |
| PBO - Combo Stratum | Percentage 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 | Through Day 60 | 0 Participants |
Secondary
Percentage of Subjects With COVID-19-related Complications
Time frame: Day 1 through Day 29
Population: Modified intent-to-treat (mITT) population included subjects who received \>= 1 dose of study drug and had \>= 1 positive SARS-CoV-2 result through Day 5.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BEM - SCO Stratum | Percentage of Subjects With COVID-19-related Complications | 3 Participants |
| PBO - SCO Stratum | Percentage of Subjects With COVID-19-related Complications | 4 Participants |
| BEM - Combo Stratum | Percentage of Subjects With COVID-19-related Complications | 0 Participants |
| PBO - Combo Stratum | Percentage of Subjects With COVID-19-related Complications | 0 Participants |
Secondary
Percentage of Subjects With COVID-19 Symptom Relapse
Time frame: Day 1 through Day 29
Population: Modified intent-to-treat (mITT) population included subjects who received \>= 1 dose of study drug and had \>= 1 positive SARS-CoV-2 result through Day 5.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BEM - SCO Stratum | Percentage of Subjects With COVID-19 Symptom Relapse | 272 Participants |
| PBO - SCO Stratum | Percentage of Subjects With COVID-19 Symptom Relapse | 265 Participants |
| BEM - Combo Stratum | Percentage of Subjects With COVID-19 Symptom Relapse | 13 Participants |
| PBO - Combo Stratum | Percentage of Subjects With COVID-19 Symptom Relapse | 12 Participants |
Secondary
Percentage of Subjects With Viral Load Rebound
Time frame: Day 1 through Day 29
Population: Modified intent-to-treat (mITT) population included subjects who received \>= 1 dose of study drug and had \>= 1 positive SARS-CoV-2 result through Day 5.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BEM - SCO Stratum | Percentage of Subjects With Viral Load Rebound | 79 Participants |
| PBO - SCO Stratum | Percentage of Subjects With Viral Load Rebound | 102 Participants |
| BEM - Combo Stratum | Percentage of Subjects With Viral Load Rebound | 4 Participants |
| PBO - Combo Stratum | Percentage of Subjects With Viral Load Rebound | 5 Participants |