Clinical trial NCT04889040: Study to Evaluate the Effects of RO7496998 (AT-527) in Non-Hospitalized Adult and Adolescent Participants With Mild or Moderate COVID-19
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID-19
Keywords: Coronavirus Disease 2019; COVID-19; antiviral drug; SARS-CoV-2; Mild to Moderate COVID-19; antiviral efficacy
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Atea Pharmaceuticals, Inc.
First posted: 2021-05-17
Enrollment: 216
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours)
timeFrame: Up to 29 days
Secondary outcomes:
measure: Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours)
timeFrame: Up to 29 days
measure: Time to Alleviation of COVID-19 Symptoms (21.5 Hours)
timeFrame: Up to 29 days
measure: Time to Alleviation of COVID-19 Symptoms (43 Hours)
timeFrame: Up to 29 days
measure: Time to One-Category Improvement of Baseline Presenting COVID-19 Symptoms
timeFrame: Up to 29 days
measure: Time to Alleviation of Individual Symptoms
timeFrame: Up to 29 days
measure: Percentage of Participants Requiring Hospitalization for COVID-19
timeFrame: Up to Day 33 visit
measure: Percentage of Participants With Greater Than or Equal to 1 COVID-19 Related Medically Attended Visit
timeFrame: Up to Day 33 visit
measure: Duration of Fever
timeFrame: Up to 29 days
measure: Percentage of Participants With COVID-19 Related Complications
timeFrame: Up to Day 33 visit
measure: Percentage of Participants With Any Post-Treatment Infection
timeFrame: Up to Day 33 visit
measure: Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA
timeFrame: Baseline and on Days 3, 5, 7 and 14
measure: Time to Cessation of SARS-CoV-2 Viral Shedding
timeFrame: Up to 14 days
measure: Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints
timeFrame: Baseline and on Days 3, 5, 7 and 14
measure: Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA
timeFrame: Day 1 prior to dosing, Day 3, Day 5, Day 7 and Day 14
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to Day 33 visit
measure: Plasma Concentration of AT-511 at Specified Timepoints
timeFrame: Up to 7 days
measure: Plasma Concentration of AT-551 at Specified Timepoints
timeFrame: Up to 7 days
measure: Plasma Concentration of AT-229 at Specified Timepoints
timeFrame: Up to 7 days
measure: Plasma Concentration of AT-273 at Specified Timepoints
timeFrame: Up to 7 days
Other outcomes:
Locations:
city: Mar Del Plata
country: Argentina
facility: Instituto Ave Pulmo
city: Châtelineau
country: Belgium
facility: Maison Médicale La Brèche
city: Erpent
country: Belgium
facility: Private Practice Dr Jean Benoit Martinot
city: Gozée
country: Belgium
facility: Medif
city: Brasilia
country: Brazil
facility: L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar
state: DF
city: Taguatinga
country: Brazil
facility: Chronos Pesquisa Clinica
state: DF
city: Recife
country: Brazil
facility: Hospital Agamenon Magalhães
state: PE
city: Curitiba
country: Brazil
facility: Hospital Nossa Senhora das Graças
state: PR
city: Sao Paulo
country: Brazil
facility: Conjunto Hospitalar do Mandaqui
state: SP
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet Copenhagen University Hospital
city: Köln
country: Germany
facility: Praxis am Ebertplatz
city: Higashiosaka-Shi
country: Japan
facility: Higashiosaka city Medical Center
city: Izumisano
country: Japan
facility: Rinku General Medical Center
city: Kanagawa
country: Japan
facility: Sagamihara Kyodo Hospital
city: Meguro-Ku
country: Japan
facility: Misyuku hospital
city: Narita
country: Japan
facility: IUHW Narita Hospital
city: Okawa-Shi
country: Japan
facility: Houjin Syadan Kouhoukai Takagi Hospital
city: Okayama
country: Japan
facility: Okayama City Hospital
city: Ome-Shi
country: Japan
facility: Ome Municipal General Hospital
city: Sakai-shi
country: Japan
facility: National Hospital Organization Kinki-Chuo Chest Medical Center
city: Shinagawa
country: Japan
facility: Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai
city: Tokyo
country: Japan
facility: Edogawa Medicare Hospital
city: Tokyo
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
city: Tokyo
country: Japan
facility: Tokyo Medical University Hachioji Medical Center
city: Torreón
country: Mexico
facility: CIMAB SA de CV
state: Coahuila
city: Guadalajara
country: Mexico
facility: Panamerican Clinical Research S.A de C.V.
state: Jalisco
city: Mexico City
country: Mexico
facility: Clinstile S.A de C.V.
state: Mexico CITY (federal District)
city: Queréaro
country: Mexico
facility: PanAmerican Clinical Research, Querétaro
state: Queretaro
city: Guadalajara
country: Mexico
facility: Instituto Jalisciense de Investigacion Clinica S.A. de C.V.
city: Mexico
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
city: Matosinhos
country: Portugal
facility: Unidade Local de Saude de Matosinhos SA
city: Bucuresti
country: Romania
facility: Prof. Dr. Matei Bals Institute of Infectious Diseases
city: Caracal
country: Romania
facility: County Hospital Caracal
city: Sibiu
country: Romania
facility: Sibiu Emergency Clinical County Hospital
city: Genève
country: Switzerland
facility: Hôpital Universitaire de Genève (HUG)
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
city: Ankara
country: Turkey
facility: Gazi Universitesi Tip Fakultesi
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Trabzon
country: Turkey
facility: Karadeniz Technical University Faculty of Medicine
city: Çankaya
country: Turkey
facility: Ankara University Medical Faculty - PPDS
city: Kharkiv
country: Ukraine
facility: Municipal Non-profit Enterprise ?City Clinical Hospital #13? of Kharkiv City Council
state: Kharkiv Governorate
city: Kharkiv
country: Ukraine
facility: Public Non-Profit Enterprise ?City Outpatient Clinic #9? of Kharkiv City Council
state: Kharkiv Governorate
city: Dnipro
country: Ukraine
facility: CNPE City Clinical Hospital #6 of DCC
state: Kholm Governorate
city: Kyiv
country: Ukraine
facility: Medical Center LLC "Harmony of Beauty"
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: CNE Kyiv City Clinical Hospital#1 of Exec. Body
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Kyiv Railway Clinical Hospital No2 of Branch Health Center of the JSC Ukrainian Rail
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Polyclinic of Center of Medical Service and Rehabilitation of State JSHC Artem
state: KIEV Governorate
city: Vinnytsya
country: Ukraine
facility: Communal Non-Commercial Enterprise Vinnytsia City Clinical Hospital 1
state: Podolia Governorate
city: Zaporizhzhia
country: Ukraine
facility: Communal Non-Profit Enterprise City Hospital #7 of Zaporizhzhia City Council
state: Tavria Okruha
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: