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
Suspended
CT.gov ID
NCT05126576
Collaborator
(none)
1,386
Enrollment
96
Locations
2
Arms
6.7
Anticipated Duration (Months)
14.4
Patients Per Site
2.2
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 DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Anticipated 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
Anticipated Primary Completion Date :
Nov 17, 2021
Anticipated Study Completion Date :
Nov 17, 2021

Arms and Interventions

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1Instituto Medico Rio CuartoCordobaArgentina5800
    2Instituto Ave PulmoMar Del PlataArgentinaB7602DCK
    3Clínica IndependenciaMunroArgentina1605
    4Instituto Medico de la Fundacion Estudios ClinicosRosarioArgentina2000
    5Clinica Mayo de U.M.C.B. S.R.LSan Miguel de TucumánArgentinaT4000IHE
    6Sanatorio Medico de Diagnostico Y TratamientoSanta FeArgentinaS3000FUJ
    7Maison Médicale La BrècheChâtelineauBelgium6200
    8Private Practice Dr Jean Benoit MartinotErpentBelgium5101
    9MedifGozéeBelgium6534
    10L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico HospitalarBrasiliaDFBrazil70200-730
    11Chronos Pesquisa ClinicaTaguatingaDFBrazil72145-450
    12Hospital das Clinicas - UFMGBelo HorizonteMGBrazil31270-901
    13Hospital Agamenon MagalhãesRecifePEBrazil52051-380
    14Hospital Nossa Senhora das GraçasCuritibaPRBrazil80810-040
    15Hospital Erasto GaertnerCuritibaPRBrazil81520-060
    16Hospital E Maternidade Celso Pierro PUCCAMPCampinasSPBrazil13060-904
    17Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDSSao Jose Do Rio PretoSPBrazil15090-000
    18CPQuali Pesquisa Clínica Sao PauloSao PauloSPBrazil01228-000
    19Institute of Infectious Diseases Emilio RibasSao PauloSPBrazil01246-900
    20Conjunto Hospitalar do MandaquiSao PauloSPBrazil02401-400
    21Aalborg UniversitetshospitalAalborgDenmark9000
    22Rigshospitalet Copenhagen University HospitalCopenhagenDenmarkDK-2100
    23Sjællands Universitetshospital, RoskildeRoskildeDenmark4000
    24Centre Hospitalier Victor DupouyArgenteuilFrance95107
    25Hôpital Saint JosephMarseilleFrance13008
    26Hopital TenonParisFrance75020
    27Klinikum Chemnitz gGmbHChemnitzGermany09116
    28Universitätsklinikum FrankfurtFrankfurtGermany60596
    29Universitätsklinikum FreiburgFreiburgGermany79106
    30Praxis am EbertplatzKölnGermany50668
    31ASST di Lecco - Presidio Ospedaliero A. Manzoni di LeccoLeccoLombardiaItaly23900
    32Ospedale San Raffaele S.r.l.MilanoLombardiaItaly20132
    33Comprensorio Amedeo Di Savoia Birago Di VischeTorinoPiemonteItaly10149
    34Funabashi Central HospitalFunabashi-ShiJapan273-0021
    35Higashiosaka city Medical CenterHigashiosaka-ShiJapan578-0947
    36Rinku General Medical CenterIzumisanoJapan598-0048
    37Sagamihara Kyodo HospitalKanagawaJapan252-5188
    38Misyuku hospitalMeguro-KuJapan153-0051
    39Nagoya City East Medical CenterNagoya-Shi Chikusa-KuJapan464-0071
    40Fujita Health University Banbuntane Hotokukai HospitalNagoya-shiJapan454-8509
    41Tokyo Metropolitan Police HospitalNakano-KuJapan164-0001
    42IUHW Narita HospitalNaritaJapan286-8520
    43Houjin Syadan Kouhoukai Takagi HospitalOkawa-ShiJapan831-0016
    44Okayama City HospitalOkayamaJapan700-8557
    45Ome Municipal General HospitalOme-ShiJapan198-0042
    46Osaka City General HospitalOsakaJapan534-0021
    47National Hospital Organization Kinki-Chuo Chest Medical CenterSakai-shiJapan591-8555
    48Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kaiShinagawaJapan140-8522
    49St. Luke's International HospitalTokyoJapan104-8560
    50Edogawa Medicare HospitalTokyoJapan133-0071
    51Center Hospital of the National Center for Global Health and MedicineTokyoJapan162-0052
    52JCHO Tokyo Shinjuku Medical CenterTokyoJapan162-8543
    53Tokyo Medical University Hachioji Medical CenterTokyoJapan193-0998
    54National Hospital Organization Kasumigaura Medical CenterTsuchiuratJapan300-0812
    55Mie Prefectural Medical CentreYokkaichiJapan510-8561
    56CIMAB SA de CVTorreónCoahuilaMexico27000
    57Panamerican Clinical Research S.A de C.V.GuadalajaraJaliscoMexico44670
    58Clinstile S.A de C.V.Mexico CityMexico CITY (federal District)Mexico06700
    59PanAmerican Clinical Research, QuerétaroQueréaroQueretaroMexico76230
    60Instituto Jalisciense de Investigacion Clinica S.A. de C.V.GuadalajaraMexico44100
    61Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranMexicoMexico
    62CEPREP; Hospital UniversitarioMonterreyMexico64460
    63Hospital Senhora da Oliveira - Guimaraes, E.P.EGuimarãesPortugal4835-044
    64Centro Hospitalar de Leiria (CHL)LeiriaPortugal2410-197
    65Unidade Local de Saude de Matosinhos SAMatosinhosPortugal4454-509
    66Prof. Dr. Matei Bals Institute of Infectious DiseasesBucurestiRomania021105
    67County Hospital CaracalCaracalRomania235200
    68Sibiu Emergency Clinical County HospitalSibiuRomania550245
    69Dr. Victor Babes Clinical Hospital of Pneumophthisiology and Infectious DiseasesTimişoaraRomania300310
    70Dr JM Engelbrecht Trial siteCape TownSouth Africa7130
    71TASK EdenGeorgeSouth Africa6530
    72Langeberg Clinical TrialsKraaifonteinSouth Africa7570
    73Clinical Projects ResearchWorcesterSouth Africa6850
    74Hôpital Universitaire de Genève (HUG)GenèveSwitzerland1211
    75Universitätsspital ZürichZürichSwitzerland8091
    76Gazi Universitesi Tip FakultesiAnkaraTurkey06100
    77Hacettepe University Medical FacultyAnkaraTurkey06100
    78Koc University Medical Faculty HospitalIstanbulTurkey34010
    79Ege University Medical FacultyIzmirTurkey35100
    80Karadeniz Technical University Faculty of MedicineTrabzonTurkey61080
    81Ankara University Medical Faculty - PPDSÇankayaTurkey06590
    82Istanbul University Cerrahpasa Medical Faculty Hospital; Tesvikiye Caddesi No:20Şi̇şli̇Turkey34365
    83Municipal Non-profit enterprise Central City Clinical Hospital of Ivano-Frankivsk City CouncilIvano-FrankivskKaterynoslav GovernorateUkraine76025
    84Municipal Non-profit Enterprise "City Clinical Hospital #13" of Kharkiv City CouncilKharkivKharkiv GovernorateUkraine61124
    85Public Non-Profit Enterprise "City Outpatient Clinic #9" of Kharkiv City CouncilKharkivKharkiv GovernorateUkraine61172
    86CNPE City Clinical Hospital #6 of DCCDniproKholm GovernorateUkraine49074
    87Municipal Non-profit Enterprise "City Clinical Hospital # 4" of Dnipro City CouncilDniproKIEV GovernorateUkraine41102
    88CNPE Ivano-Frankivsk Regional Centre of Phthisiology and Pulmonology of IFRCIvano FrankivskKIEV GovernorateUkraine76018
    89Private Enterprise Private Manufacture Company "Acinus", diagnostic and treatment centerKirovogradKIEV GovernorateUkraine25006
    90Medical Center LLC "Harmony of Beauty"KyivKIEV GovernorateUkraine01135
    91CNE Kyiv City Clinical Hospital#1 of Exec. BodyKyivKIEV GovernorateUkraine02091
    92Medical Center of LLC PreventclinicKyivKIEV GovernorateUkraine03035
    93Kyiv Railway Clinical Hospital No2 of Branch Health Center of the JSC Ukrainian RailKyivKIEV GovernorateUkraine03049
    94Polyclinic of Center of Medical Service and Rehabilitation of State JSHC ArtemKyivKIEV GovernorateUkraine04050
    95Communal Non-Commercial Enterprise Vinnytsia City Clinical Hospital 1VinnytsyaPodolia GovernorateUkraine
    96Communal Non-Profit Enterprise City Hospital #7 of Zaporizhzhia City CouncilZaporizhzhiaTavria OkruhaUkraine69118

    Sponsors and Collaborators

    • Hoffmann-La Roche

    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:
    NCT05126576
    Other Study ID Numbers:
    • CV43043
    • 2020-005759-18
    First Posted:
    Nov 19, 2021
    Last Update Posted:
    Nov 19, 2021
    Last Verified:
    Nov 1, 2021
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 19, 2021