A study to evaluate the efficacy and safety of Bemnifosbuvir in High-Risk Outpatients with COVID-19

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Atea Pharmaceuticals Inc., Atea Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

6 Mar 2023 → 30 May 2024

Decision date (initial)

2023-08-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Atea Pharmaceuticals Inc.

External identifiers

EU CT number

2023-504540-33-00

EudraCT number

2022-003268-25

ClinicalTrials.gov

NCT05629962

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Pharmacokinetic

To evaluate the efficacy of BEM compared with placebo in reducing all-cause hospitalization or all-cause death in COVID-19 outpatients receiving only supportive care.

Secondary objectives 3

1. To evaluate the efficacy of BEM compared with placebo on: - COVID-19 related hospitalization or all-cause death through Day 29 - All-cause death through Day 29 and Day 60 - COVID-19-related complications (e.g., death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis/myocarditis, cardiac failure) through Day 29 - COVID-19-related medically attended visits (hospitalization, emergency room (ER) visit, urgent care visit, physician's office visit, or telemedicine visit) or all-cause death through Day 29 and Day 60 -COVID-19 symptom relapse
2. To evaluate the antiviral activity of BEM compared with placebo on viral load rebound
3. To evaluate the safety of BEM compared with placebo

Conditions and MedDRA coding

COVID-19

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-002963-PIP01-21

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Willing and able to provide informed consent.
2. Positive SARS-CoV-2 diagnostic test (RT-PCR or validated rapid antigen test) conducted ≤ 5 days prior to randomization. Note: The test may be obtained locally. A documented historical record of positive result (RT-PCR or validated rapid antigen test) from test conducted ≤ 5 days prior to randomization is acceptable.
3. 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: • Mild COVID-19: - Symptoms of mild illness with COVID-19, which could include fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, and loss of taste or smell, without shortness of breath or dyspnea - No clinical signs indicative of moderate, severe, or critical illness severity • Moderate COVID-19: - Symptoms of moderate illness with COVID-19, which could include any symptom of mild illness or shortness of breath with exertion - Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate ≥ 20 breaths per minute, heart rate ≥ 90 beats per minute; with saturation of oxygen (SpO2) > 93% on room air -No clinical signs indicative of severe or critical illness severity
4. For females of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for 30 days after the final dose of study drug.
5. Females of childbearing potential must have a negative pregnancy test prior to initiation of study drug.
6. Subject must be able to take oral tablet medications.
7. Subject is, in the opinion of the investigator, willing and able to comply with the study drug regimen and all other study requirements.
8. Subject must be high risk, defined below. • Age ≥70 years OR • Age ≥55 years with one of the following risk factors: -Obesity (body mass index [BMI] ≥30 kg/m2) -Diabetes mellitus -Cardiovascular disease (including congenital heart disease) or hypertension (with at least one medication recommended or prescribed) -Chronic lung disease requiring routine therapy (e.g., chronic obstructive pulmonary disease [COPD], moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension) OR • Age 50 to 54 inclusive with two of the following risk factors: -Obesity (body mass index [BMI] ≥30 kg/m2) -Diabetes mellitus -Cardiovascular disease (including congenital heart disease) or hypertension (with at least one medication recommended or prescribed) -Chronic lung disease requiring routine therapy (e.g., chronic obstructive pulmonary disease [COPD], moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension) OR • Age ≥18 years with one of the following: -Down syndrome -Sickle cell disease -Dementia -Parkinson's disease, -Care home residents -One of the following immunocompromising conditions or immunosuppressive treatments: --On immunosuppressive regimens including chemotherapy for the treatment of cancer --Hematologic malignancy associated with poor response to COVID-19 vaccines (e.g., CLL, non-Hodgkin lymphoma, multiple myeloma, acute leukemia) --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 (mm3) --Moderate or severe primary immunodeficiency disorder --Active treatment with an immunosuppressive medication regimen (e.g., high-dose corticosteroids [ie, 20 mg of prednisone daily or equivalent for ≥2 weeks], alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents that are severely immunosuppressive, anti-tumor necrosis factor (TNF) blockers, biologics that are immunosuppressive) • Enrollment of high-risk adolescents (≥ 12 years to 17 years) will be allowed after the planned, pre-specified interim analysis for which 65% of the supportive-care-only stratum completed the follow-up period (Day 29). A DSMB recommendation that the study continue at this interim analysis point will trigger enrollment of adolescents.

Exclusion criteria 13

1. Female subject is pregnant or breastfeeding.
2. Clinical signs or symptoms indicative of severe or critical COVID-19 illness, including any of the following: shortness of breath at rest, respiratory rate ≥ 30 breaths per minute, heart rate ≥ 125 beats per minute, SpO2 ≤ 93% on room air, partial pressure of oxygen/ fraction of inspired oxygen (PaO2/FiO2) <300, shock (defined by systolic blood pressure < 90 mm Hg or diastolic blood pressure < 60 mm Hg or requiring vasopressors), multi-organ dysfunction/failure, respiratory distress, respiratory failure; requirement of endotracheal intubation, mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, extracorporeal membrane oxygenation (ECMO).
3. Admitted to a hospital within 90 days prior to randomization due to COVID-19 or is hospitalized (inpatient) for any reason at randomization. Note: If local policy requires COVID-19 isolation or internment in a hospital or similar facility, but subjects otherwise meet inclusion criteria, this exclusion may not apply. However, subjects under clinical observation at a clinic/study site or hospital with plans to remain in that setting overnight are not study eligible.
4. In the opinion of the investigator, is likely to experience imminent deterioration and require hospitalization within 24 hours.
5. 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, except for unblinded protocols that don't include direct acting antivirals for COVID-19 (e.g., open-label oncological regimen variations or biologic studies). Note: Prior to enrolling subjects that are on other open-label studies, it is the site's responsibility to ensure that the study criteria for that study allow for enrollment into this study.
6. Initiation or planned initiation of remdesivir for treatment of the current SARS-CoV-2 infection.
7. Requirement of any prohibited medications, as described in Section 5.7 of protocol, including either 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, mAbs) will be permitted
8. Other known active viral or bacterial infection at the time of screening, such as influenza (i.e., as verified by a locally available rapid flu test at screening) or respiratory syncytial virus (RSV). Note: This exclusion does not apply to subjects with stable chronic viral infections, such as chronic HCV or HIV providing other eligibility criteria are met.
9. Receiving dialysis or have severe renal impairment [i.e. estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 within 6 months of the screening visit, using the serum creatinine-based CKD-EPI formula]. Note: If the investigator suspects the subject may have eGFR <30 mL/min/1.73 m2, a confirmatory test should be performed at screening to confirm eligibility before the first dose of study drug.
10. History of severe hepatic impairment (Child-Pugh Class C)
11. Known allergy or hypersensitivity to components of study drug.
12. Malabsorption syndrome or other condition that would interfere with enteral absorption.
13. Any clinically significant medical condition or known laboratory abnormality that, in the opinion of the investigator, could jeopardize the safety of the subject or impact subject compliance or safety/efficacy observations in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is the proportion of subjects in the supportive-care-only population who are hospitalized for any cause or died due to any cause through Day 29

Secondary endpoints 7

1. Proportion of subjects with COVID-19-related hospitalization or who died due to any cause through Day 29
2. Proportion of subjects who died due to any cause through Day 29 and Day 60
3. Proportion of subjects with COVID-19-related complications (e.g., death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis/myocarditis, cardiac failure) through Day 29
4. Proportion of subjects with COVID-19-related 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 and Day 60
5. Proportion of subjects with COVID-19 symptom relapse through Day 29
6. Proportion of subjects with viral load rebound through Day 29
7. The incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Atea Pharmaceuticals Inc.

Sponsor organisation

Atea Pharmaceuticals Inc.

Address

225 Franklin Street Suite 2100

City

Boston

Postcode

02110-2856

Country

United States

Scientific contact point

Organisation

Atea Pharmaceuticals Inc.

Contact name

Atea Clinical Trial Information

Public contact point

Organisation

Atea Pharmaceuticals Inc.

Contact name

Atea Clinical Trial Information

Third parties 9

Atea Pharmaceuticals Inc.

Sponsor organisation

Atea Pharmaceuticals Inc.

Address

225 Franklin Street Suite 2100

City

Boston

Postcode

02110-2856

Country

United States

Scientific contact point

Organisation

Atea Pharmaceuticals Inc.

Contact name

Atea Clinical Trial Information

Public contact point

Organisation

Atea Pharmaceuticals Inc.

Contact name

Atea Clinical Trial Information

Third parties 9

Locations

6 EU/EEA countries · 33 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications