COVID-19Phase 3NCT04425460
A Multi-center,Randomized,Double-blind,Placebo-controlled,Phase 3 Study Evaluating Favipiravir in Treatment of COVID19
A Phase 3 study testing Favipiravir in people with COVID-19, run by Zhejiang Hisun Pharmaceutical Co. Ltd. at 10 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Favipiravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 256 participants
- Where
- 10 sitesin 3 countries
- Study dates
- Jun 2020to Sep 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Show all 17Show fewer
- 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.
- For further details on contraception in clinical trials, please refer to the CTFG guidance: https://www.hma.eu/fileadmin/dateien/Human_Medicines/01- About_HMA/Working_Groups/CTFG/2014_09_HM A_CTFG_Contraception.pd
- Not participating in any other drug clinical studies before completion of the present study.
Who cannot join
- 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
Show all 12Show fewer
- 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;
- Having used Favipiravir or participated in any other interventional drug clinical study within 30 days prior to first dose of study drug or having received treatments with other Investigational Medicinal Products (IMPs) or previous therapies within two weeks or five times the half-life of the drug, whichever is longer, must lead to exclusion
- 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
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
Romania6 sites
National Institute of Infectious Diseases "Prof.Dr.Matei Bals"
Bucharest, Ilfov, '021105
Infectious Diseases Hospital Cluj-Napoca
Cluj-Napoca, Cluj, 400000
"Dr.Victor Babes" Infectious Diseases and Pneumoftiziology Clinical Hospital Timisoara
Timișoara, Timiș County, '300310
"Dr.Victor Babes" Infectious Diseases and Pneumoftiziology Clinical Hospital Timisoara
Timișoara, Timiș County, 300310
Dr.Victor Babes Infectious Diseases and Pneumoftiziology Clinical Hospital Timisoara
Timișoara, Timiș County, 300310
Emergency County Hospital "Pius Brinzeu"Timisoara
Timișoara, Timiș County, 300723
China2 sites
Peking University First Hospital
Beijing, Xicheng District, 100034
The First Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Shangcheng District, 310003
Germany2 sites
Department of Internal Medicine Pneumology and infectious diseases Neukölln Clinic
Berlin, 12351
Medical clinic and polyclinic IV Hospital of the University of Munich
München, 80336
About this study
Official title: A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase III Clinical Study Evaluating the Efficacy and Safety of Favipiravir in the Treatment of Adult Patients With COVID-19-Moderate Type
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
- Being tested
- Favipiravir, Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FavipiravirDrug
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
PlaceboOther
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Favipiravir |
| Placebo | Placebo comparator | Placebo control group Favipiravir combined with supportive care recommended in the current National/Local guidelines Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Secondary outcomes (8)
Negativity in RT-PCR nucleic acid test
Time from randomization to negativity in RT-PCR nucleic acid test for 2019-nCov within 28 days of randomization;
Measured: 28 days
Time from randomization to resolution of pyrexia
Time from randomization to resolution of pyrexia (defined the same as for the primary efficacy variable; applicable to subjects with pyrexia at enrolment) within 28 days of randomization;
Measured: 28 days
Time from randomization to relief of cough
Time from randomization to relief of cough (defined the same as for the primary efficacy variable; applicable to subjects with cough at enrolment) within 28 days of randomization;
It is recommended that the severity of cough be graded as per NCI-CTCAE v5.0:
- Mild: Requires non-prescription treatment;
- Moderate: Requires medication treatment; limits instrumental activities of daily living;
- Severe: Limits self-care activities of daily living;
Measured: 28 days
Incidence of deterioration/aggravation of pneumonia
Incidence of deterioration/aggravation of pneumonia (defined as SPO2≤93% or PaO2/FiO2 ≤300 mmHg or distressed RR≥30/min without oxygen inhalation and requiring oxygen therapy or more advanced breath support) within 28 days of randomization;
Measured: 28 days
Time from randomization to relief of dyspnoea
Time from randomization to relief of dyspnoea (defined as subject-perceived improvement or resolution of dyspnoea; applicable to subjects with dyspnoea at enrolment) within 28 days of randomization;
Measured: 28 days
Rate of auxiliary oxygen therapy or non-invasive ventilation
Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization;
Measured: 28 days
ICU admission rate within 28 days of randomization
ICU admission rate within 28 days of randomization (except patients already enrolled in ICU which respect eligibility criteria);
Measured: 28 days
All-cause mortality within 28 days of randomization.
All-cause mortality within 28 days of randomization.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study startJun 2020 (estimated)
- Primary completionAug 2020 (estimated)
- Study completionSep 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a multi-center, randomized, double-blind, placebo-controlled (1:1) clinical study to explore the efficacy and safety of Favipiravir
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 256 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang Hisun Pharmaceutical Co. Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Opera CRO, a TIGERMED Group Company
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04425460
- Sponsor's protocol ID
- HS216C17(MRCT)
- Status last verified
- May 2020
- First submitted
- 28 May 2020
- Last updated
- 11 Jun 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase III Clinical Study Evaluating the Efficacy and Safety of Favipiravir in the Treatment of Adult Patients With COVID-19-Moderate Type
- ClinicalTrials.gov ID
- NCT04425460
- Acronym / sponsor ID
- HS216C17(MRCT)
- Conditions
- COVID-19
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 256 participants (estimated)
- Lead sponsor
- Zhejiang Hisun Pharmaceutical Co. Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Opera CRO, a TIGERMED Group Company
- Study start
- Jun 2020 (estimated)
- Primary completion
- Aug 2020 (estimated)
- Study completion
- Sep 2020 (estimated)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- This is a multi-center, randomized, double-blind, placebo-controlled (1:1) clinical study to explore the efficacy and safety of Favipiravir
| Arm | Type | Receives |
|---|---|---|
| Favipiravir | Experimental | Drug: FavipiravirFavipiravir 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. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo control group Favipiravir combined with supportive care recommended in the current National/Local guidelines |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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:
- 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.
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FavipiravirFavipiravir 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 | Drug | Favipiravir |
| PlaceboPlacebo 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 | Other | Placebo |
Primary outcome
Time from randomization to clinical recovery
Time frame: 28 days
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.
8 secondary outcomes
Negativity in RT-PCR nucleic acid test
Time frame: 28 days
Time from randomization to resolution of pyrexia
Time frame: 28 days
Time from randomization to relief of cough
Time frame: 28 days
Incidence of deterioration/aggravation of pneumonia
Time frame: 28 days
Time from randomization to relief of dyspnoea
Time frame: 28 days
Rate of auxiliary oxygen therapy or non-invasive ventilation
Time frame: 28 days
ICU admission rate within 28 days of randomization
Time frame: 28 days
All-cause mortality within 28 days of randomization.
Time frame: 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2020.
- Individual participant dataSharing planned: Undecided
Related trials for COVID-19
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Not yet recruitingPhase 3
Dapagliflozin for Long COVID Syndrome
COVID - 19, Long COVID Syndrome
RecruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruitingObservational study
Analysis of Coronavirus Disease 19 (COVID-19) Convalescent Plasma
Asymptomatic COVID-19 Infection Laboratory-Confirmed, Symptomatic COVID-19 Infection Laboratory-Confirmed
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Favipiravir in people with COVID-19, run by Zhejiang Hisun Pharmaceutical Co. Ltd. at 10 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Romania, China, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dionisio Barattini, MD Europe, Opera CRO (+40774012684, barattini@operacro.ro), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time from randomization to clinical recovery (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2020.