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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Terminated
CT.gov ID
NCT04889040
Collaborator
Atea Pharmaceuticals, Inc. (Industry)
1,386
Enrollment
97
Locations
2
Arms
6.7
Actual Duration (Months)
14.3
Patients Per Site
2.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1386 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Apr 28, 2021
Actual Primary Completion Date :
Nov 17, 2021
Actual Study Completion Date :
Nov 17, 2021

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 hours) [Up to 29 days]

      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). Alleviation of new symptoms 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, 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.

    Secondary Outcome Measures

    1. Time to Alleviation or Improvement of COVID-19 Symptoms (43 hours) [Up to 29 days]

      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). Alleviation of new symptoms 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, 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.

    2. Time to Alleviation of COVID-19 Symptoms (21.5 hours) [Up to 29 days]

      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.

    3. Time to Alleviation of COVID-19 Symptoms (43 hours) [Up to 29 days]

      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.

    4. Time to One-Category Improvement of Baseline Presenting COVID-19 Symptoms [Up to 29 days]

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

    5. Time to Alleviation of Individual Symptoms [Up to 29 days]

      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

    6. Proportion of Participants Requiring Hospitalization for COVID-19 [Up to 33 days]

    7. Proportion of Participants with Greater than or Equal to 1 COVID-19 Related Medically Attended Visit [Up to 33 days]

      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.

    8. Duration of Fever [Up to 29 days]

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

    9. 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.

    10. Proportion of Participants with any Post-Treatment Infection [Up to 33 days]

    11. Change from Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA [Up to 14 days]

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

    12. Time to Cessation of SARS-CoV-2 Viral Shedding [Up to 14 days]

      Defined as the length of time from randomization to first time when the virus RNA by RT-qPCR is below the limit of detection.

    13. Proportion of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints [Up to 14 days]

    14. Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA [Up to 14 days]

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

    15. Percentage of Participants with Adverse Events (AEs) [Up to 33 days]

    16. Plasma Concentration of AT-511, AT-551, AT-229 and AT-273 at Specified Timepoints [Up to 7 days]

      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)

    Eligibility Criteria

    Criteria

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Instituto Medico Rio Cuarto Cordoba Argentina 5800
    2 Instituto Ave Pulmo Mar Del Plata Argentina B7602DCK
    3 Clínica Independencia Munro Argentina 1605
    4 Instituto Medico de la Fundacion Estudios Clinicos Rosario Argentina 2000
    5 Clinica Mayo de U.M.C.B. S.R.L San Miguel de Tucumán Argentina T4000IHE
    6 Sanatorio Medico de Diagnostico Y Tratamiento Santa Fe Argentina S3000FUJ
    7 Maison Médicale La Brèche Châtelineau Belgium 6200
    8 Private Practice Dr Jean Benoit Martinot Erpent Belgium 5101
    9 Medif Gozée Belgium 6534
    10 L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar Brasilia DF Brazil 70200-730
    11 Chronos Pesquisa Clinica Taguatinga DF Brazil 72145-450
    12 Hospital das Clinicas - UFMG Belo Horizonte MG Brazil 31270-901
    13 Hospital Agamenon Magalhães Recife PE Brazil 52051-380
    14 Hospital Nossa Senhora das Graças Curitiba PR Brazil 80810-040
    15 Hospital Erasto Gaertner Curitiba PR Brazil 81520-060
    16 Hospital E Maternidade Celso Pierro PUCCAMP Campinas SP Brazil 13060-904
    17 Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS Sao Jose Do Rio Preto SP Brazil 15090-000
    18 CPQuali Pesquisa Clínica Sao Paulo Sao Paulo SP Brazil 01228-000
    19 Institute of Infectious Diseases Emilio Ribas Sao Paulo SP Brazil 01246-900
    20 Conjunto Hospitalar do Mandaqui Sao Paulo SP Brazil 02401-400
    21 Healthy Medical Center SAS Zipaquirá Colombia
    22 Aalborg Universitetshospital Aalborg Denmark 9000
    23 Rigshospitalet Copenhagen University Hospital Copenhagen Denmark DK-2100
    24 Sjællands Universitetshospital, Roskilde Roskilde Denmark 4000
    25 Centre Hospitalier Victor Dupouy Argenteuil France 95107
    26 Hôpital Saint Joseph Marseille France 13008
    27 Hopital Tenon Paris France 75020
    28 Klinikum Chemnitz gGmbH Chemnitz Germany 09116
    29 Universitätsklinikum Frankfurt Frankfurt Germany 60596
    30 Universitätsklinikum Freiburg Freiburg Germany 79106
    31 Praxis am Ebertplatz Köln Germany 50668
    32 ASST di Lecco - Presidio Ospedaliero A. Manzoni di Lecco Lecco Lombardia Italy 23900
    33 Ospedale San Raffaele S.r.l. Milano Lombardia Italy 20132
    34 Comprensorio Amedeo Di Savoia Birago Di Vische Torino Piemonte Italy 10149
    35 Funabashi Central Hospital Funabashi-Shi Japan 273-0021
    36 Higashiosaka city Medical Center Higashiosaka-Shi Japan 578-0947
    37 Rinku General Medical Center Izumisano Japan 598-0048
    38 Sagamihara Kyodo Hospital Kanagawa Japan 252-5188
    39 Misyuku hospital Meguro-Ku Japan 153-0051
    40 Nagoya City East Medical Center Nagoya-Shi Chikusa-Ku Japan 464-0071
    41 Fujita Health University Banbuntane Hotokukai Hospital Nagoya-shi Japan 454-8509
    42 Tokyo Metropolitan Police Hospital Nakano-Ku Japan 164-0001
    43 IUHW Narita Hospital Narita Japan 286-8520
    44 Houjin Syadan Kouhoukai Takagi Hospital Okawa-Shi Japan 831-0016
    45 Okayama City Hospital Okayama Japan 700-8557
    46 Ome Municipal General Hospital Ome-Shi Japan 198-0042
    47 Osaka City General Hospital Osaka Japan 534-0021
    48 National Hospital Organization Kinki-Chuo Chest Medical Center Sakai-shi Japan 591-8555
    49 Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai Shinagawa Japan 140-8522
    50 St. Luke's International Hospital Tokyo Japan 104-8560
    51 Edogawa Medicare Hospital Tokyo Japan 133-0071
    52 Center Hospital of the National Center for Global Health and Medicine Tokyo Japan 162-0052
    53 JCHO Tokyo Shinjuku Medical Center Tokyo Japan 162-8543
    54 Tokyo Medical University Hachioji Medical Center Tokyo Japan 193-0998
    55 National Hospital Organization Kasumigaura Medical Center Tsuchiurat Japan 300-0812
    56 Mie Prefectural Medical Centre Yokkaichi Japan 510-8561
    57 CIMAB SA de CV Torreón Coahuila Mexico 27000
    58 Panamerican Clinical Research S.A de C.V. Guadalajara Jalisco Mexico 44670
    59 Clinstile S.A de C.V. Mexico City Mexico CITY (federal District) Mexico 06700
    60 PanAmerican Clinical Research, Querétaro Queréaro Queretaro Mexico 76230
    61 Instituto Jalisciense de Investigacion Clinica S.A. de C.V. Guadalajara Mexico 44100
    62 Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico Mexico
    63 CEPREP; Hospital Universitario Monterrey Mexico 64460
    64 Hospital Senhora da Oliveira - Guimaraes, E.P.E Guimarães Portugal 4835-044
    65 Centro Hospitalar de Leiria (CHL) Leiria Portugal 2410-197
    66 Unidade Local de Saude de Matosinhos SA Matosinhos Portugal 4454-509
    67 Prof. Dr. Matei Bals Institute of Infectious Diseases Bucuresti Romania 021105
    68 County Hospital Caracal Caracal Romania 235200
    69 Sibiu Emergency Clinical County Hospital Sibiu Romania 550245
    70 Dr. Victor Babes Clinical Hospital of Pneumophthisiology and Infectious Diseases Timişoara Romania 300310
    71 Dr JM Engelbrecht Trial site Cape Town South Africa 7130
    72 TASK Eden George South Africa 6530
    73 Langeberg Clinical Trials Kraaifontein South Africa 7570
    74 Clinical Projects Research Worcester South Africa 6850
    75 Hôpital Universitaire de Genève (HUG) Genève Switzerland 1211
    76 Universitätsspital Zürich Zürich Switzerland 8091
    77 Gazi Universitesi Tip Fakultesi Ankara Turkey 06100
    78 Hacettepe University Medical Faculty Ankara Turkey 06100
    79 Koc University Medical Faculty Hospital Istanbul Turkey 34010
    80 Ege University Medical Faculty Izmir Turkey 35100
    81 Karadeniz Technical University Faculty of Medicine Trabzon Turkey 61080
    82 Ankara University Medical Faculty - PPDS Çankaya Turkey 06590
    83 Istanbul University Cerrahpasa Medical Faculty Hospital; Tesvikiye Caddesi No:20 Şi̇şli̇ Turkey 34365
    84 Municipal Non-profit enterprise Central City Clinical Hospital of Ivano-Frankivsk City Council Ivano-Frankivsk Katerynoslav Governorate Ukraine 76025
    85 Municipal Non-profit Enterprise "City Clinical Hospital #13" of Kharkiv City Council Kharkiv Kharkiv Governorate Ukraine 61124
    86 Public Non-Profit Enterprise "City Outpatient Clinic #9" of Kharkiv City Council Kharkiv Kharkiv Governorate Ukraine 61172
    87 CNPE City Clinical Hospital #6 of DCC Dnipro Kholm Governorate Ukraine 49074
    88 Municipal Non-profit Enterprise "City Clinical Hospital # 4" of Dnipro City Council Dnipro KIEV Governorate Ukraine 41102
    89 CNPE Ivano-Frankivsk Regional Centre of Phthisiology and Pulmonology of IFRC Ivano Frankivsk KIEV Governorate Ukraine 76018
    90 Private Enterprise Private Manufacture Company "Acinus", diagnostic and treatment center Kirovograd KIEV Governorate Ukraine 25006
    91 Medical Center LLC "Harmony of Beauty" Kyiv KIEV Governorate Ukraine 01135
    92 CNE Kyiv City Clinical Hospital#1 of Exec. Body Kyiv KIEV Governorate Ukraine 02091
    93 Medical Center of LLC Preventclinic Kyiv KIEV Governorate Ukraine 03035
    94 Kyiv Railway Clinical Hospital No2 of Branch Health Center of the JSC Ukrainian Rail Kyiv KIEV Governorate Ukraine 03049
    95 Polyclinic of Center of Medical Service and Rehabilitation of State JSHC Artem Kyiv KIEV Governorate Ukraine 04050
    96 Communal Non-Commercial Enterprise Vinnytsia City Clinical Hospital 1 Vinnytsya Podolia Governorate Ukraine
    97 Communal Non-Profit Enterprise City Hospital #7 of Zaporizhzhia City Council Zaporizhzhia Tavria Okruha Ukraine 69118

    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:
    NCT04889040
    Other Study ID Numbers:
    • CV43043
    • 2020-005759-18
    • NCT05126576
    First Posted:
    May 17, 2021
    Last Update Posted:
    Feb 4, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Hoffmann-La Roche
    Coronavirus Disease 2019; COVID-19; antiviral drug; SARS-CoV-2; Mild to Moderate COVID-19; antiviral efficacy
    Additional relevant MeSH terms:
    COVID-19

    Study Results

    No Results Posted as of Feb 4, 2022