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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT04709835
Collaborator
Atea Pharmaceuticals, Inc. (Industry)
104
Enrollment
43
Locations
2
Arms
8.3
Actual Duration (Months)
2.4
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
104 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Feb 3, 2021
Actual Primary Completion Date :
Sep 17, 2021
Actual Study Completion Date :
Oct 13, 2021

Arms and Interventions

Arm Intervention/Treatment
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.

Drug: AT-527
Results from Cohort A determined the dose and regimen to be used for Cohort B.
Other Names:
  • RO7496998

    		•
    Placebo Comparator: Placebo

    Drug: Placebo
    The dose and regimen of the placebo will match that of the respective AT-527 comparator arm.

    Outcome Measures

    Primary Outcome Measures

    1. Change from Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA [Up to Day 7]

      SARS-CoV-2 virus RNA will be measured by reverse-transcription polymerase chain reaction (RT-PCR).

    Secondary Outcome Measures

    1. Time to Cessation of SARS-CoV-2 Viral Shedding [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.

    2. Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA [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.

    3. Proportion of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints [Up to Day 7]

    4. Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA [Up to Day 7]

      AUC in the amount of SARS-CoV-2 virus RNA from baseline to the last sample timepoint.

    5. Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 hours) [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.

    6. Time to Alleviation or Improvement of COVID-19 Symptoms (43 hours) [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.

    7. Time to Alleviation of COVID-19 Symptoms (21.5 hours) [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).

    8. Time to Alleviation of COVID-19 Symptoms (43 hours) [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).

    9. Duration of Fever [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

    10. Frequency of COVID-19 Related Complications [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.

    11. Time to Alleviation of an Individual Symptom [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.

    12. Percentage of Participants with Adverse Events (AEs) [Up to 33 Days]

    13. Plasma Concentration of AT-511, AT-551, AT-229 and AT-273 [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Multiprofile Hospital for Active Treatment Puls AD PPDS Blagoevgrad Bulgaria 2700
    2 Multiprofile Hospital For Active Treatment Dr. Tota Venkova JSC Gabrovo Bulgaria 5300
    3 MHAT Dr. Atanas Dafovski AD Kardzhali Bulgaria 6600
    4 Multiprofile Hospital for Active Treatment - Prof. Dr. Paraskev Stoyanov AD Lovech Bulgaria 5500
    5 Medical center Medconsult Pleven OOD Pleven Bulgaria 5800
    6 University Multiprofile Hospital for Active Treatment Sveta Marina Pleven OOD Pleven Bulgaria 5800
    7 Multiprofile Hospital for Active Treatment Plovdiv Plovdiv Bulgaria 4003
    8 MHAT "Sv. Ivan Rilski" - Razgrad AD; Department of pnemology and phthisiatry Razgrad Bulgaria 7200
    9 Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases Dr. D. Gramatikov - Ruse Ruse Bulgaria 7002
    10 Multiprofile Hospital for Active Treatment - Samokov EOOD Samokov Bulgaria 2000
    11 Diagnostic and Consulting Center Aleksandrovska EOOD Sofia Bulgaria 1431
    12 Diagnostic Consultative CTR XX Sofia EOOD Sofia Bulgaria 1618
    13 Multiprofile Hospital for Active Treatment (MHAT) - Targovishte Targovishte Bulgaria 7700
    14 Vancouver Infectious Diseases Centre Vancouver British Columbia Canada V6Z 2C7
    15 Hamilton Medical Research Group Hamilton Ontario Canada L8M 1K7
    16 Evangelismos General Hospital of Athens Athens Greece 106 76
    17 Sotiria General Hospital of Athens; 3rd Department of Internal Medicine Athens Greece 115 27
    18 National and Kapodistrian University of Athens Athens Greece 115 28
    19 University General Hospital of Ioannina Ioannina Greece 455 00
    20 General State Hospital of Nikaia St Panteleimon Nikaia Attikis Greece 184 54
    21 Connolly Hospital Dublin Ireland 15
    22 Private Practice of Dr Liga Kozlovska Balvi Latvia LV-4501
    23 RSU Ambulance Riga Latvia LV-1007
    24 Outpatient Clinic Alma Rīga Latvia LV-1010
    25 Outpatient Clinic Adoria Rīga Latvia LV-1011
    26 The Family Physician's Practice of Dr. Maija Kozlovska Salaspils Latvia LV-2121
    27 M & M Centrs Ādaži Latvia LV-2164
    28 UAB Inmedica Kaunas Lithuania LT-48259
    29 JSC Saules Family Health Center Kaunas Lithuania LT-4949
    30 Vilnius University Hospital Santaros Klinikos Vilnius Lithuania 8406
    31 Krakowskie Centrum Medyczne Sp. z o.o. Krakow Poland 31-501
    32 Centrum Medyczne Pulawska SP. z o.o. Piaseczno Poland 05-500
    33 Centralny Szpital Klinicznty MSWiA w Warszawie Warszawa Poland 02-507
    34 Centrum Badań Klinicznych Wrocław Poland 51-162
    35 Hospital El Pilar - Grupo Quirónsalud Esplugues de Llobregat Barcelona Spain 08950
    36 Hospital Universitario Son Espases Palma de Mallorca Islas Baleares Spain 07010
    37 Hospital Costa del Sol Marbella Malaga Spain 29600
    38 Hospital Universitario La Paz - PPDS Barcelona Spain 8041
    39 Hospital Universitario Infanta Leonor Madrid Spain 28031
    40 Chapel Street Medical Centre Ashton-under-Lyne United Kingdom OL6 6EW
    41 Tower Family Healthcare - Moorgate Primary Care Ce Bury United Kingdom BL9 0NJ
    42 CPS Research Glasgow United Kingdom G20 0XA
    43 Chelsea and Westminster NHS Trust London United Kingdom SW3 6JJ

    Sponsors and Collaborators

    • Hoffmann-La Roche
    • Atea Pharmaceuticals, Inc.

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT04709835
    Other Study ID Numbers:
    • WV43042
    First Posted:
    Jan 14, 2021
    Last Update Posted:
    Nov 8, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Additional relevant MeSH terms:
    COVID-19

    Study Results

    No Results Posted as of Nov 8, 2021