- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04709835
Study to Evaluate the Effects of AT-527 in Non-Hospitalized Adult Patients With Mild or Moderate COVID-19
October 24, 2022 updated by: Hoffmann-La Roche
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
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.
Study Overview
Study Type
Interventional
Enrollment (Actual)
104
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ontario
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Hamilton, Ontario, Canada, L8M 1K7
- Hamilton Medical Research Group
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Athens, Greece, 115 28
- National and Kapodistrian University of Athens
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Nikaia Attikis, Greece, 184 54
- General State Hospital of Nikaia St Panteleimon
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Dublin, Ireland, 15
- Connolly Hospital
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Rīga, Latvia, LV-1011
- Outpatient Clinic Adoria
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Salaspils, Latvia, LV-2121
- The Family Physician's Practice of Dr. Maija Kozlovska
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Madrid, Spain, 28031
- Hospital Universitario Infanta Leonor
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Madrid, Spain, 280146
- Hospital Universitario La Paz
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Ashton-under-Lyne, United Kingdom, OL6 6EW
- Chapel Street Medical Centre
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Bury, United Kingdom, BL9 0NJ
- Tower Family Healthcare - Moorgate Primary Care Ce
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Glasgow, United Kingdom, G20 0XA
- CPS Research
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London, United Kingdom, SW3 6JJ
- Chelsea and Westminster NHS Trust
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
Participants will receive AT-527-matched placebo twice a day (BID) on Days 1-5.
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The dose and regimen of the placebo will match that of the respective AT-527 comparator arm.
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Experimental: AT-527 550 mg (1x550 mg)
Participants will receive 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.
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Results from Arm AT-527 500 mg determined the dose and regimen to be used for AT-527 1100 mg.
Other Names:
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Experimental: AT-527 1100 mg (4x275 mg)
Participants will receive 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
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Results from Arm AT-527 500 mg determined the dose and regimen to be used for AT-527 1100 mg.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
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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.
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Baseline, Day 3, Day 5, Day 7
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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
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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.
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Baseline, Day 3, Day 5, Day 7
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to Cessation of SARS-CoV-2 Viral Shedding
Time Frame: Up to Day 7
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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.
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Up to Day 7
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Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA
Time Frame: Up to Day 7
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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.
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Up to Day 7
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Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints
Time Frame: Baseline, Day 3, Day 5, Day 7
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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.
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Baseline, Day 3, Day 5, Day 7
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Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA
Time Frame: Baseline, Day 3, Day 5, Day 7
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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.
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Baseline, Day 3, Day 5, Day 7
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Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours)
Time Frame: Up to 28 Days
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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.
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Up to 28 Days
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Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours)
Time Frame: Up to 28 Days
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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.
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Up to 28 Days
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Time to Alleviation of COVID-19 Symptoms (21.5 Hours)
Time Frame: Up to 28 Days
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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.
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Up to 28 Days
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Time to Alleviation of COVID-19 Symptoms (43 Hours)
Time Frame: Up to 28 Days
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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.
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Up to 28 Days
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Duration of Fever
Time Frame: Up to 28 Days
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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.
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Up to 28 Days
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Percentage of Participants With COVID-19 Related Complications
Time Frame: Up to 33 Days
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COVID-19 related complications include death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis, myocarditis, and cardiac failure.
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Up to 33 Days
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Time to Alleviation of an Individual Symptom
Time Frame: Up to 28 Days
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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.
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Up to 28 Days
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Percentage of Participants With Adverse Events (AEs)
Time Frame: Up to 33 Days
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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.
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Up to 33 Days
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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
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AT-511 is the free base form of AT-527.
Its major metabolites are AT-551, AT-229, and AT-273.
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Day 1: pre-dose, 1 hour, 3 hours; Day 3: pre-dose; Day 5: pre-dose, 3 hours, 48 hours
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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
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AT-511 is the free base form of AT-527.
Its major metabolites are AT-551, AT-229, and AT-273.
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Day 1: pre-dose, 1 hour, 4 hours; Day 3: pre-dose; Day 5: pre-dose, 1 hour, 4 hours, 48 hours
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 3, 2021
Primary Completion (Actual)
September 17, 2021
Study Completion (Actual)
October 13, 2021
Study Registration Dates
First Submitted
January 12, 2021
First Submitted That Met QC Criteria
January 13, 2021
First Posted (Actual)
January 14, 2021
Study Record Updates
Last Update Posted (Actual)
October 26, 2022
Last Update Submitted That Met QC Criteria
October 24, 2022
Last Verified
October 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- WV43042
- 2020-005366-34 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD 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)
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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