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Study to Evaluate the Effects of AT-527 in Non-Hospitalized Adult Patients With Mild or Moderate COVID-19

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ClinicalTrials.gov Identifier: NCT04709835
Recruitment Status : Completed
First Posted : January 14, 2021
Last Update Posted : November 8, 2021
Sponsor:
Collaborator:
Atea Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE January 12, 2021
First Posted Date  ICMJE January 14, 2021
Last Update Posted Date November 8, 2021
Actual Study Start Date  ICMJE February 3, 2021
Actual Primary Completion Date September 17, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2021)
Change from Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA [ Time Frame: Up to Day 7 ]
SARS-CoV-2 virus RNA will be measured by reverse-transcription polymerase chain reaction (RT-PCR).
Original Primary Outcome Measures  ICMJE
 (submitted: January 13, 2021)
Change from Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA [ Time Frame: Cohort A: Up to Day 7; Cohorts B-E: Up to Day 14. ]
SARS-CoV-2 virus RNA will be measured by reverse-transcription polymerase chain reaction (RT-PCR).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2021)
  • Time to Cessation of SARS-CoV-2 Viral Shedding [ Time Frame: Up to Day 7 ]
    Time to cessation of viral shedding is defined as the time between the initiation of any study treatment and first time when the virus RNA by RT-PCR is below the limit of detection.
  • Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA [ Time Frame: Up to Day 7 ]
    Time to sustained non-detectable SARS-CoV-2 virus RNA is defined as the time from initiation of study treatment to the last timepoint when the virus RNA by RT-PCR is below the limit of detection.
  • Proportion of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints [ Time Frame: Up to Day 7 ]
  • Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA [ Time Frame: Up to Day 7 ]
    AUC in the amount of SARS-CoV-2 virus RNA from baseline to the last sample timepoint.
  • Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 hours) [ Time Frame: Up to 28 Days ]
    Alleviation of symptoms is defined as the length of time taken from start of treatment to the point at which a Score of 0 or 1 has been maintained for a duration of at least 21.5 hours. Improvement of symptoms is defined as at least a single category improvement from baseline on the Likert scale.
  • Time to Alleviation or Improvement of COVID-19 Symptoms (43 hours) [ Time Frame: Up to 28 Days ]
    Alleviation of symptoms is defined as the length of time taken from start of treatment to the point at which a Score of 0 or 1 has been maintained for a duration of at least 43 hours. Improvement of symptoms is defined as at least a single category improvement from baseline on the Likert scale.
  • Time to Alleviation of COVID-19 Symptoms (21.5 hours) [ Time Frame: Up to 28 Days ]
    Alleviation of symptoms is defined as the length of time taken from start of treatment to the point at which the following criteria are met and maintained for at least 21.5 hours: Score of 0 or 1 on Items 1-12 of the COVID-19 Symptom Diary (without consideration for presence of pre-existing symptoms).
  • Time to Alleviation of COVID-19 Symptoms (43 hours) [ Time Frame: Up to 28 Days ]
    Alleviation of symptoms is defined as the length of time taken from start of treatment to the point at which the following criteria are met and maintained for at least 43 hours: Score of 0 or 1 on Items 1-12 of the COVID-19 Symptom Diary (without consideration for presence of pre-existing symptoms).
  • Duration of Fever [ Time Frame: Up to 28 Days ]
    Defined as the time to return to an afebrile state (temperature ≤ 37.5°C) maintained for at least 21.5 hours
  • Frequency of COVID-19 Related Complications [ Time Frame: Up to 33 Days ]
    Examples of COVID-19 related complications include death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis, myocarditis, and cardiac failure.
  • Time to Alleviation of an Individual Symptom [ Time Frame: Up to 28 Days ]
    Time to alleviation of an individual symptom is defined as the time taken from the start of treatment to the point at which the following criterion is met and maintained (for each individual symptom) for at least 21.5 hours:
    • Score of 0 or 1 for Items 1-12 of the COVID-19 Symptom Diary.
    • Score of 0 for Items 13 and 14 of the COVID-19 Symptom Diary.
  • Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 33 Days ]
  • Plasma Concentration of AT-511, AT-551, AT-229 and AT-273 [ Time Frame: Up to Day 7 ]
    AT-511 is the free base form of AT-527. Its major metabolites are AT-551, AT-229, and AT 273.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2021)
  • Time to Cessation of SARS-CoV-2 Viral Shedding [ Time Frame: Cohort A: Up to Day 7; Cohorts B-E: Up to Day 14. ]
    Time to cessation of viral shedding is defined as the time between the initiation of any study treatment and first time when the virus RNA by RT-PCR is below the limit of detection.
  • Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA [ Time Frame: Cohort A: Up to Day 7; Cohorts B-E: Up to Day 14. ]
    Time to sustained non-detectable SARS-CoV-2 virus RNA is defined as the time from initiation of study treatment to the last timepoint when the virus RNA by RT-PCR is below the limit of detection.
  • Proportion of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints [ Time Frame: Cohort A: Up to Day 7; Cohorts B-E: Up to Day 14. ]
  • Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA [ Time Frame: Cohort A: Up to Day 7; Cohorts B-E: Up to Day 14. ]
    AUC in the amount of SARS-CoV-2 virus RNA from baseline to the last sample timepoint.
  • Time to Alleviation of COVID-19 Symptoms [ Time Frame: Up to 28 Days ]
    Alleviation of symptoms is defined as the length of time taken from start of treatment to the point at which the following criteria are met and maintained for at least 21.5 hours: Score of 0 or 1 on Items 1-12 of the COVID-19 Symptom Diary.
  • Duration of Fever [ Time Frame: Up to 28 Days ]
    Defined as the time to return to an afebrile state (temperature ≤ 37.5°C) maintained for at least 21.5 hours
  • Frequency of COVID-19 Related Complications [ Time Frame: Up to 33 Days ]
    Examples of COVID-19 related complications include death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis, myocarditis, and cardiac failure.
  • Time to Alleviation of an Individual Symptom [ Time Frame: Up to 28 Days ]
    Time to alleviation of an individual symptom is defined as the time taken from the start of treatment to the point at which the following criterion is met and maintained (for each individual symptom) for at least 21.5 hours:
    • Score of 0 or 1 for Items 1-12 of the COVID-19 Symptom Diary.
    • Score of 0 for Items 13 and 14 of the COVID-19 Symptom Diary.
  • Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 33 Days ]
  • Plasma Concentration of AT-511, AT-551, AT-229 and AT-273 [ Time Frame: Cohort A: Up to Day 7; Cohorts B-E: Up to Day 8 ]
    AT-511 is the free base form of AT-527. Its major metabolites are AT-551, AT-229, and AT 273.
  • Relationship Between Plasma Concentration of AT- 273 and Anti-Viral Activity [ Time Frame: Cohort A: Up to Day 7; Cohorts B-E: Up to Day 8 ]
    Drug exposure response relationship will be explored through modelling (PK-PD modelling) to evaluate the relationship between plasma concentrations of AT-273 and viral load at each timepoint
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Effects of AT-527 in Non-Hospitalized Adult Patients With Mild or Moderate COVID-19
Official Title  ICMJE A Phase II Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Antiviral Activity, Safety, Pharmacokinetics, and Efficacy of RO7496998 (AT-527) in Non-Hospitalized Adult Patients With Mild or Moderate COVID-19
Brief Summary This randomized study evaluates the antiviral activity, safety, efficacy and pharmacokinetics of AT-527 versus a placebo in participants with mild or moderate coronavirus disease (COVID-19) who are not hospitalized.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Drug: AT-527
    Results from Cohort A determined the dose and regimen to be used for Cohort B.
    Other Name: RO7496998
  • Drug: Placebo
    The dose and regimen of the placebo will match that of the respective AT-527 comparator arm.
Study Arms  ICMJE
  • Experimental: AT-527
    Participants will receive 550 mg AT-527 twice a day (BID) in Cohort A and 1100 mg AT-527 BID in Cohort B.
    Intervention: Drug: AT-527
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 1, 2021)
104
Original Estimated Enrollment  ICMJE
 (submitted: January 13, 2021)
220
Actual Study Completion Date  ICMJE October 13, 2021
Actual Primary Completion Date September 17, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Positive SARS-CoV-2 diagnostic test (RT-PCR or rapid antigen test)at screening
  • Has symptoms consistent with mild or moderate COVID-19, as determined by the investigator, with onset ≤5 days prior to randomization

Exclusion Criteria:

  • Clinical signs indicative of COVID-19 illness requiring hospitalization, defined as any of the following: shortness of breath at rest, respiratory rate ≥30, heart rate ≥125, peripheral capillary oxygen saturation ≤93% on room air
  • Treatment with a therapeutic agent against SARS-CoV-2 including, but not limited to, other direct acting antivirals, convalescent plasma, monoclonal antibodies against SARS CoV-2, or intravenous immunoglobulin within 3 months or less than 5 drug elimination half-lives (whichever is longer) prior to screening
  • Requirement, in the opinion of the investigator, for any of the prohibited medications during the study
  • Use of hydroxychloroquine or amiodarone within 3 months of screening
  • Pregnant or breastfeeding, or intending to become pregnant during the study or within 30 days after the final dose of AT-527. Women of childbearing potential must have a negative urine pregnancy test result at screening
  • Abnormal laboratory test results at screening
  • Clinically significant abnormal ECG, as determined by the Investigator, at screening
  • Planned procedure or surgery during the study
  • Known allergy or hypersensitivity to study drug or drug product excipients
  • Substance abuse, as determined by the investigator, within 12 months prior to screening
  • Poor peripheral venous access
  • Malabsorption syndrome or other condition that would interfere with enteral absorption
  • Any clinically significant history of epistaxis within the last 3 months and/or history of being hospitalized due to epistaxis of any previous occasion
  • History of anaphylaxis
  • Any uncontrolled serious medical condition or other clinically significant abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Canada,   Greece,   Ireland,   Latvia,   Lithuania,   Poland,   Spain,   United Kingdom
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT04709835
Other Study ID Numbers  ICMJE WV43042
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Atea Pharmaceuticals, Inc.
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP