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

A Multicenter, Phase III Randomized, Double-Blind, Placebo-Controlled, Outpatient Study to Evaluate the Efficacy, Safety, Antiviral Activity of RO7496998 (AT-527) in Patients With Mild or Moderate COVID-19

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 Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Placebo; Drug: RO7496998

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Mar Del Plata, Argentina, B7602DCK
    • Instituto Ave Pulmo
• Belgium
  • Châtelineau, Belgium, 6200
    • Maison Médicale La Brèche
  • Erpent, Belgium, 5101
    • Private Practice Dr Jean Benoit Martinot
  • Gozée, Belgium, 6534
    • Medif
• Brazil
  • DF
    • Brasilia, DF, Brazil, 70200-730
      • L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar
    • Taguatinga, DF, Brazil, 72145-450
      • Chronos Pesquisa Clínica
  • PE
    • Recife, PE, Brazil, 52051-380
      • Hospital Agamenon Magalhaes
  • PR
    • Curitiba, PR, Brazil, 80810-040
      • Hospital Nossa Senhora Das Gracas
  • SP
    • Sao Paulo, SP, Brazil, 02401-400
      • Conjunto Hospitalar do Mandaqui
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital
  • Copenhagen, Denmark, DK-2100
    • Rigshospitalet Copenhagen University Hospital
• Germany
  • Köln, Germany, 50668
    • Praxis am Ebertplatz
• Japan
  • Higashiosaka-Shi, Japan, 578-0947
    • Higashiosaka City Medical Center
  • Izumisano, Japan, 598-0048
    • Rinku General Medical Center
  • Kanagawa, Japan, 252-5188
    • Sagamihara Kyodo Hospital
  • Meguro-Ku, Japan, 153-0051
    • Misyuku hospital
  • Narita, Japan, 286-8520
    • Iuhw Narita Hospital
  • Okawa-Shi, Japan, 831-0016
    • Houjin Syadan Kouhoukai Takagi Hospital
  • Okayama, Japan, 700-8557
    • Okayama City Hospital
  • Ome-Shi, Japan, 198-0042
    • Ome Municipal General Hospital
  • Sakai-shi, Japan, 591-8555
    • National Hospital Organization Kinki-chuo Chest Medical Center
  • Shinagawa, Japan, 140-8522
    • Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai
  • Tokyo, Japan, 193-0998
    • Tokyo Medical University Hachioji Medical Center
  • Tokyo, Japan, 162-0052
    • Center Hospital of the National Center for Global Health and Medicine
  • Tokyo, Japan, 133-0071
    • Edogawa Medicare Hospital
• Mexico
  • Guadalajara, Mexico, 44100
    • Instituto Jalisciense de Investigacion Clinica S.A. de C.V.
  • Mexico, Mexico
    • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  • Coahuila
    • Torreón, Coahuila, Mexico, 27000
      • CIMAB SA de CV
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44670
      • Panamerican Clinical Research S.A de C.V.
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 06700
      • Clinstile S.A de C.V.
  • Queretaro
    • Queréaro, Queretaro, Mexico, 76230
      • PanAmerican Clinical Research, Queretaro
• Portugal
  • Matosinhos, Portugal, 4454-509
    • Unidade Local de Saúde de Matosinhos SA
• Romania
  • Bucuresti, Romania, 021105
    • Prof. Dr. Matei Bals Institute of Infectious Diseases
  • Caracal, Romania, 235200
    • County Hospital Caracal
  • Sibiu, Romania, 550245
    • Sibiu Emergency Clinical County Hospital
• Switzerland
  • Genève, Switzerland, 1211
    • Hôpital Universitaire de Genève (HUG)
  • Zürich, Switzerland, 8091
    • UniversitätsSpital Zürich
• Turkey
  • Ankara, Turkey, 06100
    • Gazi Universitesi Tip Fakultesi
  • Izmir, Turkey, 35100
    • Ege University Medical Faculty
  • Trabzon, Turkey, 61080
    • Karadeniz Technical University Faculty of Medicine
  • Çankaya, Turkey, 06590
    • Ankara University Medical Faculty - PPDS
• Ukraine
  • KIEV Governorate
    • Kyiv, KIEV Governorate, Ukraine, 01135
      • Medical Center LLC "Harmony of Beauty"
    • Kyiv, KIEV Governorate, Ukraine, 02091
      • CNE Kyiv City Clinical Hospital#1 of Exec. Body
    • Kyiv, KIEV Governorate, Ukraine, 03049
      • Kyiv Railway Clinical Hospital No2 of Branch Health Center of the JSC Ukrainian Rail
    • Kyiv, KIEV Governorate, Ukraine, 04050
      • Polyclinic of Center of Medical Service and Rehabilitation of State JSHC Artem
  • Kharkiv Governorate
    • Kharkiv, Kharkiv Governorate, Ukraine, 61124
      • Municipal Non-profit Enterprise ?City Clinical Hospital #13? of Kharkiv City Council
    • Kharkiv, Kharkiv Governorate, Ukraine, 61172
      • Public Non-Profit Enterprise ?City Outpatient Clinic #9? of Kharkiv City Council
  • Kholm Governorate
    • Dnipro, Kholm Governorate, Ukraine, 49074
      • CNPE City Clinical Hospital #6 of DCC
  • Podolia Governorate
    • Vinnytsya, Podolia Governorate, Ukraine
      • Communal Non-Commercial Enterprise Vinnytsia City Clinical Hospital 1
  • Tavria Okruha
    • Zaporizhzhia, Tavria Okruha, Ukraine, 69118
      • Communal Non-Profit Enterprise City Hospital #7 of Zaporizhzhia City Council

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO7496998 (AT-527); Orally administered, 550 mg twice daily (BID) for 5 days	Drug: RO7496998; 275 mg tablets; Other Names: AT-527
Placebo Comparator: Placebo; The dose and regimen of the placebo will match that of AT-527.	Drug: Placebo; Matching tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 29 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 29 days
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.	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.	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.	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.	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.	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.	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.	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.	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.	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)	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.	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.	Baseline and on Days 3, 5, 7 and 14
Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA		Day 1 prior to dosing, Day 3, Day 5, Day 7 and Day 14
Percentage of Participants With Adverse Events (AEs)		Up to Day 33 visit
Plasma Concentration of AT-511 at Specified Timepoints	AT-511 is the free base form of RO7496998 (AT-527).	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)	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)	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)	Up to 7 days

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Atea Pharmaceuticals, Inc.
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2021
• Primary Completion (Actual): December 2, 2021
• Study Completion (Actual): December 2, 2021

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 17, 2021

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Coronavirus Disease 2019; COVID-19; antiviral drug; SARS-CoV-2; Mild to Moderate COVID-19; antiviral efficacy
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: CV43043; 2020-005759-18 (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: No
• Studies a U.S. FDA-regulated device product: No