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NCT04396106

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

Terminated Phase 2 Results posted Last updated 9 March 2023
What this trial tests

Phase 2 trial testing AT-527 in COVID-19 in 83 participants. Terminated before completion.

Timeline
26 May 2020
Primary endpoint
10 January 2022
28 February 2022

Quick facts

Lead sponsorAtea Pharmaceuticals, Inc.
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment83
Start date26 May 2020
Primary completion10 January 2022
Estimated completion28 February 2022
Sites37 locations across South Africa, Ukraine, Belgium, Moldova, Argentina, Romania, Spain, United States

Drugs / interventions tested

Conditions studied

Sponsor

Atea Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
AT-527 - 550 mg BID3
Placebo for 550 mg BID4
Placebo for 1100 mg BID0
Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab Secondary · Through Day 14

Change in the viral load as measured by swab of the upper part of the pharynx.

Change from baseline to Day 2
GroupValue95% CI
AT-527 - 550 mg BID-0.55± 1.175
Placebo for 550 mg BID-0.02± 1.838
Placebo for 1100 mg BID-1.37± 1.57
Change from baseline to Day 5
GroupValue95% CI
AT-527 - 550 mg BID-1.00± 1.316
Placebo for 550 mg BID-0.80± 1.853
Placebo for 1100 mg BID-2.51± 0.66
Change from baseline to Day 8
GroupValue95% CI
AT-527 - 550 mg BID-1.64± 1.534
Placebo for 550 mg BID-1.38± 1.281
Placebo for 1100 mg BID-3.78± 1.39
Change from baseline to Day 10
GroupValue95% CI
AT-527 - 550 mg BID-1.72± 1.734
Placebo for 550 mg BID-2.26± 1.452
Placebo for 1100 mg BID-4.78± 2.13
Change from baseline to Day 12
GroupValue95% CI
AT-527 - 550 mg BID-2.13± 2.065
Placebo for 550 mg BID-2.08± 1.584
Placebo for 1100 mg BID-4.78± 2.13
Change from baseline to Day 14
GroupValue95% CI
AT-527 - 550 mg BID-2.61± 1.873
Placebo for 550 mg BID-2.26± 1.747
Placebo for 1100 mg BID-4.13± 1.21

Adverse events — posted to ClinicalTrials.gov

Time frame: 28 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AT-527 - 550 mg BID
Serious: 5/40 (13%)
Deaths: 0/40
Placebo for 550 mg BID
Serious: 3/40 (8%)
Deaths: 2/40
AT-527 - 1100 mg BID
Serious: 0
Deaths: 0
Placebo for 1100 mg BID
Serious: 1/2 (50%)
Deaths: 1/2

Serious adverse events (12 terms)

ReactionSystemAT-527 - 550 mg BIDPlacebo for 550 mg BIDAT-527 - 1100 mg BIDPlacebo for 1100 mg BID
Oxygen saturation decreasedInvestigations
Abdominal abscessInfections and infestations
Acute kidney injuryRenal and urinary disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
COVID-19 pneumoniaInfections and infestations
Haemodynamic instabilityVascular disorders
Hyperglycaemic hyperosmolar nonketotic syndromeMetabolism and nutrition disorders
PneumoniaInfections and infestations
Respiratory failureRespiratory, thoracic and mediastinal disorders
RhabdomyolysisMusculoskeletal and connective tissue disorders
Supraventricular tachycardiaCardiac disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Other adverse events (19 terms — click to expand)

ReactionSystemAT-527 - 550 mg BIDPlacebo for 550 mg BIDAT-527 - 1100 mg BIDPlacebo for 1100 mg BID
Blood triglycerides increasedInvestigations
Alanine aminotransferase increasedInvestigations
Blood cholesterol increasedInvestigations
Aspartate aminotransferase increasedInvestigations
DiarrhoeaGastrointestinal disorders
Oxygen saturation decreasedInvestigations
Lipase increasedInvestigations
EnterocolitisGastrointestinal disorders
FlatulenceGastrointestinal disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
Injection site haemorrhageGeneral disorders
Sinus tachycardiaCardiac disorders
PneumoniaInfections and infestations
UrticariaSkin and subcutaneous tissue disorders
HepatitisHepatobiliary disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
N-terminal prohormone brain natriuretic peptide increasedInvestigations
Pulmonary embolismRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Oxygen saturation decreased, Abdominal abscess, Acute kidney injury, Acute respiratory failure, COVID-19 pneumonia, Haemodynamic instability, Hyperglycaemic hyperosmolar nonketotic syndrome, Pneumonia.

Data from ClinicalTrials.gov NCT04396106 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. AT-527, a Double Prodrug of a Guanosine Nucleotide Analog, Is a Potent Inhibitor of SARS-CoV-2 <i>In Vitro</i> and a Promising Oral Antiviral for Treatment of COVID-19.
    Good SS, Westover J, Jung KH, Zhou XJ, et al · · 2021 · cited 112× · PMID 33558299 · DOI 10.1128/aac.02479-20
  2. SARS-CoV-2 Antiviral Therapy.
    Tao K, Tzou PL, Nouhin J, Bonilla H, et al · · 2021 · cited 80× · PMID 34319150 · DOI 10.1128/cmr.00109-21
  3. Races of small molecule clinical trials for the treatment of COVID-19: An up-to-date comprehensive review.
    Hu S, Jiang S, Qi X, Bai R, et al · · 2022 · cited 68× · PMID 34762760 · DOI 10.1002/ddr.21895
  4. An Update on Antiviral Therapy Against SARS-CoV-2: How Far Have We Come?
    Indari O, Jakhmola S, Manivannan E, Jha HC. · · 2021 · cited 65× · PMID 33762954 · DOI 10.3389/fphar.2021.632677
  5. Oral antiviral treatments for COVID-19: opportunities and challenges.
    Rahmah L, Abarikwu SO, Arero AG, Essouma M, et al · · 2022 · cited 53× · PMID 35871712 · DOI 10.1007/s43440-022-00388-7
  6. An update of anti-viral treatment of COVID-19
    Şimşek-Yavuz S, Komsuoğlu Çelikyurt FI. · · 2021 · cited 51× · PMID 34391321 · DOI 10.3906/sag-2106-250
  7. Therapeutics for COVID-19 and post COVID-19 complications: An update.
    Basu D, Chavda VP, Mehta AA. · · 2022 · cited 44× · PMID 35136858 · DOI 10.1016/j.crphar.2022.100086
  8. Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review.
    Al-Horani RA, Kar S. · · 2020 · cited 33× · PMID 32993173 · DOI 10.3390/v12101092

Verify or expand the search:

Other trials of AT-527

Trials testing the same drug.

Other recruiting trials for COVID-19

Currently open trials in the same condition.

Other Atea Pharmaceuticals, Inc. trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing