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

COVID-19 Clinical Trial

— MORNINGSKY  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04889040
• Other study ID #: CV43043
• Secondary ID: 2020-005759-18
• Status: Terminated
• Phase: Phase 3
• Start date: April 28, 2021
• Est. completion date: December 2, 2021

Study information

• Verified date: March 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT05126576

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 216
• Est. completion date: December 2, 2021
• Est. primary completion date: December 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• RO7496998
275 mg tablets
• Placebo
Matching tablets

Locations

Country	Name	City	State
Argentina	Instituto Ave Pulmo	Mar Del Plata
Belgium	Maison Médicale La Brèche	Châtelineau
Belgium	Private Practice Dr Jean Benoit Martinot	Erpent
Belgium	Medif	Gozée
Brazil	L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar	Brasilia	DF
Brazil	Hospital Nossa Senhora das Graças	Curitiba	PR
Brazil	Hospital Agamenon Magalhães	Recife	PE
Brazil	Conjunto Hospitalar do Mandaqui	Sao Paulo	SP
Brazil	Chronos Pesquisa Clinica	Taguatinga	DF
Denmark	Aalborg Universitetshospital	Aalborg
Denmark	Rigshospitalet Copenhagen University Hospital	Copenhagen
Germany	Praxis am Ebertplatz	Köln
Japan	Higashiosaka city Medical Center	Higashiosaka-Shi
Japan	Rinku General Medical Center	Izumisano
Japan	Sagamihara Kyodo Hospital	Kanagawa
Japan	Misyuku hospital	Meguro-Ku
Japan	IUHW Narita Hospital	Narita
Japan	Houjin Syadan Kouhoukai Takagi Hospital	Okawa-Shi
Japan	Okayama City Hospital	Okayama
Japan	Ome Municipal General Hospital	Ome-Shi
Japan	National Hospital Organization Kinki-Chuo Chest Medical Center	Sakai-shi
Japan	Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai	Shinagawa
Japan	Center Hospital of the National Center for Global Health and Medicine	Tokyo
Japan	Edogawa Medicare Hospital	Tokyo
Japan	Tokyo Medical University Hachioji Medical Center	Tokyo
Mexico	Instituto Jalisciense de Investigacion Clinica S.A. de C.V.	Guadalajara
Mexico	Panamerican Clinical Research S.A de C.V.	Guadalajara	Jalisco
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico
Mexico	Clinstile S.A de C.V.	Mexico City	Mexico CITY (federal District)
Mexico	PanAmerican Clinical Research, Querétaro	Queréaro	Queretaro
Mexico	CIMAB SA de CV	Torreón	Coahuila
Portugal	Unidade Local de Saude de Matosinhos SA	Matosinhos
Romania	Prof. Dr. Matei Bals Institute of Infectious Diseases	Bucuresti
Romania	County Hospital Caracal	Caracal
Romania	Sibiu Emergency Clinical County Hospital	Sibiu
Switzerland	Hôpital Universitaire de Genève (HUG)	Genève
Switzerland	Universitätsspital Zürich	Zürich
Turkey	Gazi Universitesi Tip Fakultesi	Ankara
Turkey	Ankara University Medical Faculty - PPDS	Çankaya
Turkey	Ege University Medical Faculty	Izmir
Turkey	Karadeniz Technical University Faculty of Medicine	Trabzon
Ukraine	CNPE City Clinical Hospital #6 of DCC	Dnipro	Kholm Governorate
Ukraine	Municipal Non-profit Enterprise ?City Clinical Hospital #13? of Kharkiv City Council	Kharkiv	Kharkiv Governorate
Ukraine	Public Non-Profit Enterprise ?City Outpatient Clinic #9? of Kharkiv City Council	Kharkiv	Kharkiv Governorate
Ukraine	CNE Kyiv City Clinical Hospital#1 of Exec. Body	Kyiv	KIEV Governorate
Ukraine	Kyiv Railway Clinical Hospital No2 of Branch Health Center of the JSC Ukrainian Rail	Kyiv	KIEV Governorate
Ukraine	Medical Center LLC "Harmony of Beauty"	Kyiv	KIEV Governorate
Ukraine	Polyclinic of Center of Medical Service and Rehabilitation of State JSHC Artem	Kyiv	KIEV Governorate
Ukraine	Communal Non-Commercial Enterprise Vinnytsia City Clinical Hospital 1	Vinnytsya	Podolia Governorate
Ukraine	Communal Non-Profit Enterprise City Hospital #7 of Zaporizhzhia City Council	Zaporizhzhia	Tavria Okruha

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Atea Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Argentina,  Belgium,  Brazil,  Denmark,  Germany,  Japan,  Mexico,  Portugal,  Romania,  Switzerland,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants With Adverse Events (AEs)		Up to Day 33 visit
Secondary	Plasma Concentration of AT-511 at Specified Timepoints	AT-511 is the free base form of RO7496998 (AT-527).	Up to 7 days
Secondary	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
Secondary	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
Secondary	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