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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04709835
Recruitment Status : Completed
First Posted : January 14, 2021
Results First Posted : October 13, 2022
Last Update Posted : October 26, 2022
Sponsor:
Collaborator:
Atea Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche

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
COVID-19 Drug: AT-527 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
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 : February 3, 2021
Actual Primary Completion Date : September 17, 2021
Actual Study Completion Date : October 13, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Participants will receive AT-527-matched placebo twice a day (BID) on Days 1-5.
Drug: Placebo
The dose and regimen of the placebo will match that of the respective AT-527 comparator arm.

Experimental: AT-527 550 mg (1x550 mg)
Participants will receive 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.
Drug: AT-527
Results from Arm AT-527 500 mg determined the dose and regimen to be used for AT-527 1100 mg.
Other Name: RO7496998

Experimental: AT-527 1100 mg (4x275 mg)
Participants will receive 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Drug: AT-527
Results from Arm AT-527 500 mg determined the dose and regimen to be used for AT-527 1100 mg.
Other Name: RO7496998




Primary Outcome Measures :
  1. Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo [ Time Frame: Baseline, Day 3, Day 5, Day 7 ]
    SARS-CoV-2 virus RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) from nasopharyngeal (NP) swabs. The change from baseline was estimated from an ANCOVA model with baseline viral load as a covariate. Reported here is the adjusted mean change from baseline. A negative change from baseline indicates an improvement.

  2. Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 1100 mg and Pooled Placebo [ Time Frame: Baseline, Day 3, Day 5, Day 7 ]
    SARS-CoV-2 virus RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) from NP swabs. The change from baseline was estimated from an ANCOVA model with baseline viral load as a covariate. Reported here is the adjusted mean change from baseline. A negative change from baseline indicates an improvement.


Secondary Outcome Measures :
  1. Time to Cessation of SARS-CoV-2 Viral Shedding [ Time Frame: Up to Day 7 ]
    Time to cessation of viral shedding was defined as the time between the initiation of any study treatment and the first time when a negative or below the limit of detection RT-PCR test result was obtained. RT-PCR was measured from NP swabs. Median, 25th and 75th percentiles were estimated from the Kaplan-Meier curve.

  2. 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 was defined as the time between the initiation of any study treatment and first time when a negative or below the limit of detection test result by RT-PCR is obtained after which no positive test above or equal to the limit of detection was reported. RT-PCR was measured from NP swabs. Median, 25th and 75th percentiles were estimated from the Kaplan-Meier curve.

  3. Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints [ Time Frame: Baseline, Day 3, Day 5, Day 7 ]
    Reported here is the percentage of participants with a positive virus RNA by RT-PCR test result above or equal to the limit of quantification (LOQ). RT-PCR was measured from NP swabs.

  4. Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA [ Time Frame: Baseline, Day 3, Day 5, Day 7 ]
    AUC is the amount of SARS-CoV-2 virus RNA from baseline to the last sample timepoint and was calculated using the trapezoidal method. RT-PCR was measured from NP swabs.

  5. Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours) [ Time Frame: Up to 28 Days ]
    COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe).Time to alleviation or improvement is defined as the length of time taken from start of treatment to the point at which all of the following three criteria are met and maintained for a concurrent duration of at least 21.5 hours: "new" symptoms with a score of 0 or 1; "pre- existing and worsened due to COVID-19" symptoms with at least a single category improvement from baseline; "pre-existing and not worsened due to COVID-19" symptoms remaining the same or at least a single category improvement from baseline.

  6. Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours) [ Time Frame: Up to 28 Days ]
    COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation or improvement is defined as the length of time taken from start of treatment to the point at which all of the following three criteria are met and maintained for a concurrent duration of at least 43 hours: "new" symptoms with a score of 0 or 1; "pre- existing and worsened due to COVID-19" symptoms with at least a single category improvement from baseline; "pre-existing and not worsened due to COVID-19" symptoms remaining the same or at least a single category improvement from baseline.

  7. Time to Alleviation of COVID-19 Symptoms (21.5 Hours) [ Time Frame: Up to 28 Days ]
    COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation of COVID-19 symptoms is defined as the length of time taken from start of treatment to the point at which the following criterion is met and maintained for at least 21.5 hours: Score of 0 or 1 on Items 1-12 of the COVID-19 Symptom Diary, regardless of if the symptom is pre-existing or new.

  8. Time to Alleviation of COVID-19 Symptoms (43 Hours) [ Time Frame: Up to 28 Days ]
    COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation of COVID-19 symptoms is defined as the length of time taken from start of treatment to the point at which the following criterion is met and maintained for at least 43 hours: Score of 0 or 1 on Items 1-12 of the COVID-19 Symptom Diary, regardless of if the symptom is pre-existing or new.

  9. Duration of Fever [ Time Frame: Up to 28 Days ]
    Duration of fever was defined as the time from start of treatment to return to an afebrile state (temperature ≤ 37.5°C) maintained for at least 21.5 hours.

  10. Percentage of Participants With COVID-19 Related Complications [ Time Frame: Up to 33 Days ]
    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 [ Time Frame: Up to 28 Days ]
    The COVID-19 Symptom Diary included the following 14 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, diarrhea, sense of smell over the past 7 days and sense of taste over the past 7 days. The severity of items 1-12 was recorded on a 4-point Likert scale (none=0, mild=1, moderate=2, severe=3). Items 13-14 were recorded on a 3-point Likert scale (same as usual=0, less than usual=1, no sense=2). Time to alleviation of an individual symptom was defined as the time taken from the start of treatment to the point at which the following criterion was 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) [ Time Frame: Up to 33 Days ]
    An AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any of the following: any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition not present at baseline or related to a protocol-mandated intervention.

  13. Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 [ Time Frame: Day 1: pre-dose, 1 hour, 3 hours; Day 3: pre-dose; Day 5: pre-dose, 3 hours, 48 hours ]
    AT-511 is the free base form of AT-527. Its major metabolites are AT-551, AT-229, and AT-273.

  14. Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 [ Time Frame: Day 1: pre-dose, 1 hour, 4 hours; Day 3: pre-dose; Day 5: pre-dose, 1 hour, 4 hours, 48 hours ]
    AT-511 is the free base form of AT-527. Its major metabolites are AT-551, AT-229, and AT-273.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04709835


Locations
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Canada, Ontario
Hamilton Medical Research Group
Hamilton, Ontario, Canada, L8M 1K7
Greece
National and Kapodistrian University of Athens
Athens, Greece, 115 28
General State Hospital of Nikaia St Panteleimon
Nikaia Attikis, Greece, 184 54
Ireland
Connolly Hospital
Dublin, Ireland, 15
Latvia
Outpatient Clinic Adoria
Rīga, Latvia, LV-1011
The Family Physician's Practice of Dr. Maija Kozlovska
Salaspils, Latvia, LV-2121
Spain
Hospital Universitario La Paz
Madrid, Spain, 280146
Hospital Universitario Infanta Leonor
Madrid, Spain, 28031
United Kingdom
Chapel Street Medical Centre
Ashton-under-Lyne, United Kingdom, OL6 6EW
Tower Family Healthcare - Moorgate Primary Care Ce
Bury, United Kingdom, BL9 0NJ
CPS Research
Glasgow, United Kingdom, G20 0XA
Chelsea and Westminster NHS Trust
London, United Kingdom, SW3 6JJ
Sponsors and Collaborators
Hoffmann-La Roche
Atea Pharmaceuticals, Inc.
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:
Study Protocol  [PDF] September 17, 2021
Statistical Analysis Plan  [PDF] September 1, 2021

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04709835    
Other Study ID Numbers: WV43042
2020-005366-34 ( EudraCT Number )
First Posted: January 14, 2021    Key Record Dates
Results First Posted: October 13, 2022
Last Update Posted: October 26, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
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)

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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:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases