Study to Evaluate the Effects of RO7496998 (AT-527) in Non-Hospitalized Adult and Adolescent Participants With Mild or Moderate COVID-19

Phase 3TerminatedNCT04889040

Hoffmann-La Roche216 enrolled

Overview

This study will evaluate the efficacy, safety, antiviral activity, and pharmacokinetics of study drug RO7496998 (AT-527) compared to placebo in non-hospitalized adult and adolescent participants with mild to moderate coronavirus disease 2019 (COVID-19) in the outpatient setting.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

216

Conditions

COVID-19

Interventions

RO7496998DRUG

275 mg tablets

PlaceboDRUG

Matching tablets

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Positive SARS-CoV-2 diagnostic test (RT-PCR or validated rapid antigen test) ≤72 hours prior to randomization * At least three of the following symptoms of at least moderate (score ≥2 as per COVID-19 Symptom Diary) intensity: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills or sweats, feeling hot or feverish, nausea, vomiting, or diarrhea. * Has symptoms consistent with mild or moderate COVID-19, as determined by the investigator, with onset ≤5 days before dosing on Day 1 Exclusion Criteria: * Clinical signs indicative of COVID-19 illness requiring hospitalization * Admitted to a hospital prior to randomization or is hospitalized (inpatient) at randomization due to COVID-19 * In the opinion of the investigator, is likely to experience imminent deterioration and require hospitalization * Treatment with an investigational drug within 5 half-lives or 3 months (whichever is longer) of randomization * Treatment with a COVID-19 therapeutic agent including, but not limited to, other direct or indirect acting antivirals against SARS-CoV-2 (such as remdesivir or favipiravir), systemic or inhaled steroids (such as dexamethasone or inhaled budesonide), colchicine, ivermectin, interferons, convalescent plasma, monoclonal antibodies against SARS CoV-2 or interleukin 6 (IL-6), intravenous immunoglobulin or other EUA-approved treatments within 3 months or less than 5 drug elimination half-lives (whichever is longer) prior to the screening visit * Concomitant use of P-glycoprotein inhibitors or inducers listed as prohibited therapy in the protocol * Known allergy or hypersensitivity to components of study drug * Abnormal laboratory test results at screening * Requirement of any prohibited medications during the study * Other known active viral or bacterial infection at the time of screening, such as influenza * Any clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, could jeopardize the safety of the patient or affect patient compliance or safety/efficacy observations during the study * COVID-19 vaccination within ≤ 40-days prior to enrollment (second dose if applicable)

Locations (50)

Outcomes

Primary Outcomes

Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours)

COVID-19 symptoms will be evaluated using the COVID-19 Symptom Diary (questions 1-12). The severity of each COVID-19 symptom will be recorded on a Likert scale (i.e none/mild/moderate/severe). The time to alleviation or improvement of COVID-19 symptoms is defined as follows: for new symptoms, it is defined as the length of time taken from randomization to the point at which a Score of 0 or 1 has been maintained for a duration of at least 21.5 hours. For preexisting symptoms, it is defined as the time from randomization to when a patient's symptoms have been maintained or improved (requires at least a single category improvement from baseline on the COVID-19 Symptom Diary Likert scale) for a duration of 21.5 hours.

Time frame: Up to 29 days

Secondary Outcomes

Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours)

COVID-19 symptoms will be evaluated using the COVID-19 Symptom Diary (questions 1-12). The severity of each COVID-19 symptom will be recorded on a Likert scale (i.e none/mild/moderate/severe). The time to alleviation or improvement of COVID-19 symptoms is defined as follows: for new symptoms, it is defined as the length of time taken from randomization to the point at which a Score of 0 or 1 has been maintained for a duration of at least 43 hours. For preexisting symptoms, it is defined as the time from randomization to when a patient's symptoms have been maintained or improved (requires at least a single category improvement from baseline on the COVID-19 Symptom Diary Likert scale) for a duration of 43 hours.

Time frame: Up to 29 days

Time to Alleviation of COVID-19 Symptoms (21.5 Hours)

Time from randomization 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.

Time frame: Up to 29 days

Time to Alleviation of COVID-19 Symptoms (43 Hours)

Time from randomization 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.

Data from ClinicalTrials.gov

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Instituto Ave Pulmo

Mar del Plata, Argentina

Maison Médicale La Brèche

Châtelineau, Belgium

Private Practice Dr Jean Benoit Martinot

Erpent, Belgium

Medif

Gozée, Belgium

L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar

Brasília, Federal District, Brazil

Chronos Pesquisa Clinica

Taguatinga, Federal District, Brazil

Hospital Nossa Senhora das Graças

Curitiba, Paraná, Brazil

Hospital Agamenon Magalhães

Recife, Pernambuco, Brazil

Conjunto Hospitalar do Mandaqui

São Paulo, São Paulo, Brazil

Aalborg Universitetshospital

Aalborg, Denmark

...and 40 more locations

Time frame: Up to 29 days

Time to One-Category Improvement of Baseline Presenting COVID-19 Symptoms

Time from randomization to the point at which symptoms (Items 1-12 of the COVID-19 Symptom Diary) have improved by at least one category from baseline on the COVID-19 Symptom Diary Likert scale, maintained for at least 21.5 hours.

Time frame: Up to 29 days

Time to Alleviation of Individual Symptoms

Time from randomization 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 1-14 of the COVID-19 Symptom Diary

Time frame: Up to 29 days

Percentage of Participants Requiring Hospitalization for COVID-19

Hospitalizations for COVID-19 are defined as SAEs for which the investigator has cited that the suspected cause was the disease under study and where there is a non-missing hospital admission date.

Time frame: Up to Day 33 visit

Percentage of Participants With Greater Than or Equal to 1 COVID-19 Related Medically Attended Visit

Medically attended visit is defined as hospitalization, emergency room (ER) visit, urgent care visit, physician's office visit, or telemedicine visit, with the primary reason for the visit being COVID-19.

Time frame: Up to Day 33 visit

Duration of Fever

Time to return to an afebrile state (temperature ≤ 37.5°C) maintained for at least 21.5 hours.

Time frame: Up to 29 days

Percentage of Participants With COVID-19 Related Complications

COVID-related complications are defined as death, hospitalization, pneumonia, sepsis, coagulopathy, pericarditis/myocarditis and cardiac failure. Pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis/myocarditis, and cardiac failure were adjudicated per blinded manual medical review of events by an internal adjudication team before study readout.

Time frame: Up to Day 33 visit

Percentage of Participants With Any Post-Treatment Infection

Post-treatment infections were defined as any treatment-emergent adverse event with a primary system organ class of infections and infestations.

Time frame: Up to Day 33 visit

Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA

SARS-CoV-2 virus RNA will be measured by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR)

Time frame: Baseline and on Days 3, 5, 7 and 14

Time to Cessation of SARS-CoV-2 Viral Shedding

Defined as time from randomization to the first time when a negative qualitative virus RNA by RT-PCR test result is obtained.

Time frame: Up to 14 days

Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints

Defined as percentage of participants with a positive qualitative virus RNA by RT-PCR.

Time frame: Baseline and on Days 3, 5, 7 and 14

Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA

Time frame: Day 1 prior to dosing, Day 3, Day 5, Day 7 and Day 14

Percentage of Participants With Adverse Events (AEs)

Time frame: Up to Day 33 visit

Plasma Concentration of AT-511 at Specified Timepoints

AT-511 is the free base form of RO7496998 (AT-527).

Time frame: Up to 7 days

Plasma Concentration of AT-551 at Specified Timepoints

AT-511 is the free base form of RO7496998 (AT-527). Major metabolites are AT-551, AT-229, and AT-273 (a surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010)

Time frame: Up to 7 days

Plasma Concentration of AT-229 at Specified Timepoints

AT-511 is the free base form of RO7496998 (AT-527). Major metabolites are AT-551, AT-229, and AT-273 (a surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010)

Time frame: Up to 7 days

Plasma Concentration of AT-273 at Specified Timepoints

AT-511 is the free base form of RO7496998 (AT-527). Major metabolites are AT-551, AT-229, and AT-273 (a surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010)

Time frame: Up to 7 days