A Multi-center,Randomized,Double-blind,Placebo-controlled,Phase 3 Study Evaluating Favipiravir in Treatment of COVID19

NCT04425460 | Unknown Phase 3

• 1 other identifier: HS216C17(MRCT)
• Study Type: interventional
• Target: 256
• Locations: 3 countries
• Sites: 10

Brief Summary

This is a multi-center, randomized, double-blind, placebo-controlled, phase III clinical study to evaluate the efficacy of Favipiravir combined with supportive care for adult patients with COVID-19-Moderate type.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• Time from randomization to clinical recovery

  The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory rate and SPO2 and relief of cough (where there are relevant abnormal symptoms at enrolment) that is maintained for at least 72h. Criteria for normalization or relief: * Pyrexia (body temperature): axillary ≤37℃，or oral≤37.5℃，or rectal or tympanic ≤38℃; * Respiratory rate: ≤24/min without oxygen inhalation; * SPO2: \>94% without oxygen inhalation; * Cough: Subject-perceived improvement or resolution of cough.

  28 days

Secondary Outcomes (8)

• Negativity in RT-PCR nucleic acid test

  28 days

• Time from randomization to resolution of pyrexia

  28 days

• Time from randomization to relief of cough

  28 days

• Incidence of deterioration/aggravation of pneumonia

  28 days

• Time from randomization to relief of dyspnoea

  28 days

Study Arms (2)

Favipiravir

EXPERIMENTAL

Favipiravir Tablets, 200 mg/tablet Favipiravir combined with supportive care recommended in the current National/Local guidelines. Favipiravir dosage and method of administration: Day 1: 1800mg, BID; Day 2 and thereafter: 600mg, TID, for a maximum of 14 days.

Drug: Favipiravir

Placebo

PLACEBO COMPARATOR

Placebo control group Favipiravir combined with supportive care recommended in the current National/Local guidelines

Other: Placebo

Interventions

Favipiravir DRUG

Favipiravir combined with supportive care recommended in the current National/Local guidelines. Favipiravir dosage and method of administration: Day 1 1800 mg x2; Day 2 up to a maximum of 14 days 600 mg x 3

Favipiravir

Placebo OTHER

Placebo combined with supportive care recommended in the current National/Local guidelines. Placebo dosage and method of administration: Day 1 1800 mg x2; Day 2 up to a maximum of 14 days 600 mg x 3

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participating in the clinical study; fully understanding and being fully informed of the study and having signed the Informed Consent Form (ICF); willingness and capability to complete all the study procedures;
• Age 18-75 years (inclusive) at the time of signing ICF;
• Being confirmed with COVID-19-Moderate type according to Competent Authority and Ministry of Health and respective country guidelines and recommendations reported in Appendix 1 (a, b, c, d) to the present protocol. Based on comprehensive analysis and judgement taking into account both the epidemiological history and clinical manifestations, the diagnosis is to be confirmed for suspected cases or suspected cases/clinically diagnosed cases with all of the following etiological evidences:
• Positivity in RT-PCR 2019-nCov test on respiratory tract specimens;
• High homology with known gene sequence of 2019-nCov in viral gene sequencing on respiratory tract specimens.
• Chest imaging (CT as first option or X-ray if CT not possible)-documented pneumonia; if CT cannot be performed, Pneumonia confirmed by X-ray may be used. The method of chest imaging pneumonia diagnosis must be consistent all through the study period;
• Patients with pyrexia (axillary ≥37℃ or oral ≥ 37.5℃, or tympanic or rectal≥38℃) or either respiratory rate \>24/min and \<30/min or cough; For not hospitalized patients, the Investigator should maintain the detection method consistent through study period. In addition, the Investigator should maintain the data collection and quality compliant with GCP requirements.
• The interval between symptoms onset and randomization is no more than 10 days; symptoms onset is primarily based on pyrexia, and can be based on cough or other related symptoms for patients without experiencing pyrexia following onset (it is strongly recommended that the interval between symptoms onset and randomization should not exceed 5 days);
• For female subjects: evidence of post-menopause, or, for pre-menopause subjects, negative pre-treatment serum or urine pregnancy test. Menopause is defined as amenorrhea for at least 12 months without other medical cause, with the following age-specific requirements:
• For female subjects aged \<50 years: menopause for at least 12 months following withdrawal of exogenous hormonal therapy, with LH or FSH within the post-menopausal ranges, or having undergone any contraceptive surgery (bilateral oophorectomy or hysterectomy);
• For female subjects aged ≥ 50 years: menopause for at least 12 months following withdrawal of exogenous hormonal therapy, or having undergone radiotherapy-induced oophorectomy with amenorrhea \>1 year, or having undergone chemotherapy-induced menopause with amenorrhea\>1 year, or having undergone any contraceptive surgery (bilateral oophorectomy or hysterectomy).
• Eligible subjects of child-bearing age (male or female) must agree to take effective contraceptive measures (including hormonal contraception, barrier methods or abstinence) with his/her partner during the study period and for at least 3 months (in male) and 1 month (in female)following the last study treatment; in addition:
• For female participants of childbearing potential only highly effective methods (failure rate \< 1 %) plus one barrier method is allowed throughout the period of relevant systemic exposure with Favipiravir. Double barrier methods alone are not considered as highly effective. Additionally, pregnancy testing at baseline only is not deemed sufficient and must be repeated more frequently, at least if clinical signs of pregnancy occur and at follow-up / end of study.
• male participants, if vasectomized or not, must wear a condom each time having heterosexual intercourse throughout the period of relevant systemic exposure with Favipiravir (as it is distributed to seminal fluid).
• male participant must be instructed not to have intercourse with pregnant women throughout the period of relevant systemic exposure with Favipiravir.

You may not qualify if:

• Where, in the opinion of the investigator, participation in this study will not be in the best interest of the subject, or any other circumstances that prevent the subject from participating in the study safely;
• Refractory nausea, vomiting, or chronic gastrointestinal disorders, inability to swallow the study drug or having undergone extensive bowel resection which may affect adequate absorption of Favipiravir;
• Severe liver disease: underlying liver cirrhosis or alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevated over 5 times the ULN;
• Gout/history of gout or hyperuricemia (above the ULN);
• Oxygen saturation (SPO2) ≤93% or arterial oxygen partial pressure (PaO2)/ fraction of inspired O2 (FiO2) ≤300 mmHg;
• Known allergy or hypersensitivity to Favipiravir or any of its excipients, or to placebo excipients
• Known severe renal impairment \[creatinine clearance (CrCl) \<30 mL/min\] or having received continuous renal replacement therapy, hemodialysis or peritoneal dialysis;
• Possibility of the subject being transferred to a non-study hospital within 72h;
• Pregnant or lactating women;
• Persons, who were placed in an institution due to official or legal orders should be excluded
• Persons, who are dependent on the sponsor, the investigator or the trial site, meaning that the voluntary nature of their consent is no longer guaranteed, must be excluded from participation

Sponsors & Collaborators

• Zhejiang Hisun Pharmaceutical Co. Ltd.: lead
• Opera CRO, a TIGERMED Group Company: collaborator

Study Sites (10)

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Shangcheng District, 310003, China

Location

Peking University First Hospital

Beijing, Xicheng District, 100034, China

Location

Department of Internal Medicine Pneumology and infectious diseases Neukölln Clinic

Berlin, 12351, Germany

Location

Medical clinic and polyclinic IV Hospital of the University of Munich

München, 80336, Germany

Location

Infectious Diseases Hospital Cluj-Napoca

Cluj-Napoca, Cluj, 400000, Romania

Location

National Institute of Infectious Diseases "Prof.Dr.Matei Bals"

Bucharest, Ilfov, '021105, Romania

Location

"Dr.Victor Babes" Infectious Diseases and Pneumoftiziology Clinical Hospital Timisoara

Timișoara, Timiș County, '300310, Romania

Location

"Dr.Victor Babes" Infectious Diseases and Pneumoftiziology Clinical Hospital Timisoara

Timișoara, Timiș County, 300310, Romania

Location

Dr.Victor Babes Infectious Diseases and Pneumoftiziology Clinical Hospital Timisoara

Timișoara, Timiș County, 300310, Romania

Location

Emergency County Hospital "Pius Brinzeu"Timisoara

Timișoara, Timiș County, 300723, Romania

Location

MeSH Terms

Conditions

COVID-19

Interventions

favipiravir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Dionisio Barattini, MD Europe, Opera CRO

CONTACT

+40774012684; barattini@operacro.ro

Emanuel Dogaru, CPM, Opera CRO

CONTACT

+40724345115; dogaru@operacro.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multi-center, randomized, double-blind, placebo-controlled (1:1) clinical study to explore the efficacy and safety of Favipiravir

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 11, 2020
• Study Start: June 1, 2020
• Primary Completion: August 1, 2020
• Study Completion: September 1, 2020
• Last Updated: June 11, 2020

Record last verified: 2020-05

Locations

CN (2); DE (2); RO (6)