Safety and Efficacy of AT-527 in Subjects With Moderate Coronavirus Disease (COVID-19) in a Hospital Setting

NCT04396106 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: AT-03A-001
• Study Type: interventional
• Target: 83
• Locations: 10 countries
• Sites: 37

Brief Summary

The objectives of this study are to evaluate the safety, tolerability, antiviral activity and efficacy of AT-527 in adult subjects ≥18 years of age with moderate COVID-19 and risk factors for poor outcomes (such as obesity (BMI\>30), hypertension, diabetes or asthma). Eligible subjects will be randomized to blinded AT-527 (nucleotide analog) tablets or matching placebo tablets to be administered orally for 5 days. Part A will evaluate an AT-527 dose of 550 mg BID and Part B will evaluate a second dose of AT-527 (1100 mg BID). Local supportive standard of care (SOC) will be allowed for all subjects. Efficacy, antiviral activity and safety observations will be compared for treatment with active AT-527 tablets vs. placebo tablets.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• Proportions (Active vs. Placebo) of Subjects With Progressive Respiratory Insufficiency (PRI) on or Before Day 14.

  Progressive respiratory insufficiency defined as a ≥ 2-tier increase in respiratory support methods required to maintain satisfactory oxygenation (SpO2 ≥ 93%), using the 6-tier hierarchical scale of respiratory support methods, within the 14-day study period. Level 1:Normal oxygenation on room air (SpO2 ≥93), no need for supplemental O2 Level 2:Persistent hypoxemia on room air (SpO2 \<93) with requirement for low-level supplemental O2 by nasal cannula/mask (up to 2L/min) to maintain SpO2 ≥93 Level 3:Requirement for higher levels of passive supplemental O2 by nasal cannula or mask (≥2 L/min) to maintain SpO2 ≥93 Level 4:Requirement for oxygenation by positive-pressure devices Level 5:Required invasive respiratory support (intubated mechanical ventilation or ECMO) Level 6:Death

  Day 14

Secondary Outcomes (1)

• Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab

  Through Day 14

Study Arms (4)

AT-527 - 550 mg BID

ACTIVE COMPARATOR

Part A

Drug: AT-527

Placebo for 550 mg BID

PLACEBO COMPARATOR

Part A

Other: Placebo

AT-527 - 1100 mg BID

ACTIVE COMPARATOR

Part B

Drug: AT-527

Placebo for 1100 mg BID

PLACEBO COMPARATOR

Part B

Other: Placebo

Interventions

AT-527 DRUG

One 550 mg tablet of AT-527 administered every \~12 hours (twice a day) for a total of 5 days

AT-527 - 550 mg BID

Placebo OTHER

One placebo tablet administered every \~12 hours (twice a day) for a total of 5 days

Placebo for 550 mg BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalized or in a hospital-affiliated confinement facility
• SARS-CoV-2 positive
• Initial COVID-19 symptom onset within 5 days prior to Screening
• SpO2 ≥ 93% on room air or requires ≤ 2L/min oxygen by nasal cannula or mask to maintain SpO2 ≥ 93%
• Must also have a history of at least one of the following known risk factors for poor outcomes: obesity (BMI\>30), hypertension, diabetes or asthma.

You may not qualify if:

• Severe or critical COVID-19 illness: RR ≥30, HR ≥125, SpO2 \<93% on room air or requires \>2L/min oxygen by nasal cannula or mask to maintain SpO2 ≥93%, systolic blood pressure \< 90 mm Hg, diastolic blood pressure \< 60 mm Hg or PaO2/FiO2 \<300
• Requires mechanical ventilation
• Lobar or segmental consolidation on chest imaging.
• Treatment with other drugs thought to possibly have activity against SARS-CoV-2
• ALT or AST \> 5 x upper limit of normal (ULN)
• Female subject is pregnant or breastfeeding
• Has received or is expected to receive any dose of a SARS-CoV-2 vaccine before the Day 14 visit (Part B).

Sponsors & Collaborators

• Atea Pharmaceuticals, Inc.: lead

Study Sites (37)

Atea Study Site

Scottsdale, Arizona, 85258, United States

Location

Atea Study Site

Davis, California, 95817, United States

Location

Atea Study Site

Los Angeles, California, 90017, United States

Location

Atea Study Site

Washington D.C., District of Columbia, 20037, United States

Location

Atea Study Site

Orlando, Florida, 32804, United States

Location

Atea Study Site

Atlanta, Georgia, 30303, United States

Location

Atea Study Site

Chicago, Illinois, 60611, United States

Location

Atea Study Site

Chicago, Illinois, 60612, United States

Location

Atea Study Site

Boston, Massachusetts, 02115, United States

Location

Atea Study Site

Butte, Montana, 59701, United States

Location

Atea Study Site

Charlotte, North Carolina, 28204, United States

Location

Atea Study Site

Cincinnati, Ohio, 45219, United States

Location

Atea Study Site

Columbus, Ohio, 43203, United States

Location

Atea Study Site

Charleston, South Carolina, 29425, United States

Location

Atea Study Site

Columbia, South Carolina, 29203, United States

Location

Atea Study Site

Rosario, Argentina

Location

Atea Study Site

Vicente López, Argentina

Location

Atea Study Site

Brussels, Belgium

Location

Atea Study Site

Mechelen, Belgium

Location

Atea Study Site

Belo Horizonte, Brazil

Location

Atea Study Site

Brasília, Brazil

Location

Atea Study Site

Campo Largo, Brazil

Location

Atea Study Site

Porto Alegre, Brazil

Location

Atea Study Site

São Paulo, Brazil

Location

Atea Study Site

Cairo, Egypt

Location

Atea Study Site

Chisinau, Moldova

Location

Atea Study Site

Bucharest, Romania

Location

Atea Study Site

Bloemfontein, South Africa

Location

Atea Study Site

Cape Town, South Africa

Location

Atea Study Site

Centurion, South Africa

Location

Atea Study Site

George, South Africa

Location

Atea Study Site

Worcester, South Africa

Location

Atea Study Site

Barcelona, Spain

Location

Atea Study Site

Madrid, Spain

Location

Atea Study Site

Pozuelo de Alarcón, Spain

Location

Atea Study Site

Brovary, Ukraine

Location

Atea Study Site

Kyiv, Ukraine

Location

Related Publications (1)

• Horga A, Kuritzkes DR, Kowalczyk JJ, Pietropaolo K, Belanger B, Lin K, Perkins K, Hammond J. Phase II study of bemnifosbuvir in high-risk participants in a hospital setting with moderate COVID-19. Future Virol. 2023 Jun;18(8):489-500. doi: 10.2217/fvl-2023-0064. Epub 2023 Jun 23.

  PMID: 38051993 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

AT-511

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Study was prematurely discontinued. At the time of study discontinuation, only 2 subjects were enrolled in Part B and both received placebo.

Results Point of Contact

• Title: Atea Clinical Trials
• Organization: Atea Pharmaceuticals, Inc.

ateaclinicaltrials@ateapharma.com

1-857-284-8891

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2020
• First Posted: May 20, 2020
• Study Start: May 26, 2020
• Primary Completion: January 10, 2022
• Study Completion: February 28, 2022
• Last Updated: March 9, 2023
• Results First Posted: March 9, 2023

Record last verified: 2023-02

Locations

EG (1); AR (2); ZA (5); BE (2); BR (5); MO (1); RO (1); ES (3); UA (2); US (15)