COVID-19Phase 3NCT04336904
Clinical Study To Evaluate The Performance And Safety Of Favipiravir in COVID-19
A Phase 3 study testing Favipiravir in people with COVID-19, run by Giuliano Rizzardini at 1 site in Italy.
Trial summary
This study evaluates treatment with 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
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 25 Mar 2020to Jul 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 Italian Ministry of Health guidelines and to the recommendations reported in Appendix 1 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/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; Note: The above criterion would be subject to any update of the Competent Authority and Italian Ministry of Health guidelines and to the recommendations reported in Appendix 1 to the present protocol. In case any new etiologically detection methods/criteria or any new detectable specimens become available after confirmed diagnosis, the new methods or new specimens may or may not be used at the discretion of the investigator.
- Note: Sputum specimen is preferred for RT-PCR test of 2019-nCov nucleic acid; the specific type of respiratory tract specimen (e.g., nasopharyngeal swabs, sputum, lower respiratory tract secretions) is to be selected based on the conditions of the local laboratory.
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- The type of specimen and detection method for 2019-nCov should remain consistent for the same subject receiving study treatment.
- 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 axillary 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 all through the 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;
- 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 7 days following the last study treatment;
- Not participating in any other interventional 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;
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- Known severe renal impairment [creatinine clearance (CcCl) <30 mL/min] or having received continuous renal replacement therapy, hemodialysis or peritoneal dialysis; CcCl is to be calculated by the following Cockcroft-Gault formula only when the serum creatinine is>1.5×ULN
- 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.
- Note: Considering that COVID-19 requires immediate treatment, absence of severe hepatic/renal disorders (e.g., cirrhosis, long-term dialysis) in the medical record can be used as an evidence for eligibility determination. It is recommended that hepatic function and creatinine be examined whenever possible.
Trial locations and contacts
1 site in 1 country.
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 Patients With COVID-19-Moderate Type
This study evaluates treatment with Favipiravir combined with supportive care for adult patients with COVID-19-moderate type.
Read the detailed description
This is a double-blind, placebo controlled, multicenter study that evaluates the performance and safety of the Favipiravir combined with supportive care for adult patients with COVID-19-moderate type.
- Conditions
- COVID-19
- Being tested
- Favipiravir, Placebo
- Keywords
- COVID-19
- 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
Dosage and method of administration: Day 1: 1800mg, BID; Day 2 and thereafter: 600mg, TID, for a maximum of 14 days.
Where the subject has experienced an adverse event related to liver injury of grade≥3 (NCI CTCAE v5.0), the dose is to be reduced to 600mg BID. It is at the discretion of the investigator whether or not to perform dose reduction based on how the subject is benefiting from study treatment. The subject should be discontinued from treatment if he/she re-experiences any adverse event related to liver injury of grade≥3 after dose reduction
PlaceboOther
Dosage and method of administration: Day 1: 1800mg, BID; Day 2 and thereafter: 600mg, TID, for a maximum of 14 days.
Where the subject has experienced an adverse event related to liver injury of grade≥3 (NCI CTCAE v5.0), the dose is to be reduced to 600mg BID. It is at the discretion of the investigator whether or not to perform dose reduction based on how the subject is benefiting from study treatment. The subject should be discontinued from treatment if he/she re-experiences any adverse event related to liver injury of grade≥3 after dose reduction
| Study group | Role | What they receive |
|---|---|---|
| Favipiravir | Experimental | Experimental: Favipiravir Dosage and method of administration: Day 1: 1800mg, BID; Day 2 and thereafter: 600mg, TID, for a maximum of 14 days.
Where the subject has experienced an adverse event related to liver injury of grade≥3 (NCI CTCAE v5.0), the dose is to be reduced to 600mg BID. It is at the discretion of the investigator whether or not to perform dose reduction based on how the subject is benefiting from study treatment. The subject should be discontinued from treatment if he/she re-experiences any adverse event related to liver injury of grade≥3 after dose reduction. Receives: Drug: Favipiravir |
| Placebo | Placebo comparator | Comparator: Placebo Dosage and method of administration: Day 1: 1800mg, BID; Day 2 and thereafter: 600mg, TID, for a maximum of 14 days.
Where the subject has experienced an adverse event related to liver injury of grade≥3 (NCI CTCAE v5.0), the dose is to be reduced to 600mg BID. It is at the discretion of the investigator whether or not to perform dose reduction based on how the subject is benefiting from study treatment. The subject should be discontinued from treatment if he/she re-experiences any adverse event related to liver injury of grade≥3 after dose reduction 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 72 hours.
Measured: 90 days
Secondary outcomes (8)
Time from randomization to 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
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 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
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
- Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization
Measured: 28 days
ICU admission rate
ICU admission rate within 28 days of randomization
Measured: 28 days
Mortality
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 posted7 Apr 2020
- Study start25 Mar 2020
- Primary completionJul 2020 (estimated)
- Study completionJul 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 in the treatment of adult subjects with COVID-19-moderate type. Subjects within 10 days of COVID-19 onset will be screened, and be randomized as early as possible within 24 hours following screen success. It is planned to randomize 100 subjects in an 1:1 ratio. Subjects in the test group will receive supportive care recommended in the current guidelines+Favipiravir, and subjects in the control group will receive supportive care recommended in the current guidelines+placebo control; the efficacy and safety of Favipiravir versus the placebo in the treatment of COVID-19-moderate type will be compared.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Giuliano Rizzardini
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Giuliano Rizzardini, ASST Fatebenefratelli Sacco
- Investigators
- Giuliano Rizzardini, Md, Principal investigator, ASST Fatebenefratelli Sacco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04336904
- Sponsor's protocol ID
- HS216C17-PHASE III
- Status last verified
- Apr 2020
- First submitted
- 3 Apr 2020
- Last updated
- 8 Apr 2020
- Results posted
- No
- Data monitoring committee
- 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 8 Apr 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 Patients With COVID-19-Moderate Type
- ClinicalTrials.gov ID
- NCT04336904
- Acronym / sponsor ID
- HS216C17-PHASE III
- Conditions
- COVID-19
- Keywords
- COVID-19
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Giuliano RizzardiniUniversity, hospital or other
- Study start
- 25 Mar 2020 (actual)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Jul 2020 (estimated)
- First posted
- 7 Apr 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 study evaluates treatment with Favipiravir combined with supportive care for adult patients with COVID-19-moderate type.
Detailed description
This is a double-blind, placebo controlled, multicenter study that evaluates the performance and safety of the 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, care provider)
- 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 in the treatment of adult subjects with COVID-19-moderate type. Subjects within 10 days of COVID-19 onset will be screened, and be randomized as early as possible within 24 hours following screen success. It is planned to randomize 100 subjects in an 1:1 ratio. Subjects in the test group will receive supportive care recommended in the current guidelines+Favipiravir, and subjects in the control group will receive supportive care recommended in the current guidelines+placebo control; the efficacy and safety of Favipiravir versus the placebo in the treatment of COVID-19-moderate type will be compared.
| Arm | Type | Receives |
|---|---|---|
| Favipiravir | Experimental | Drug: FavipiravirExperimental: Favipiravir Dosage and method of administration: Day 1: 1800mg, BID; Day 2 and thereafter: 600mg, TID, for a maximum of 14 days. Where the subject has experienced an adverse event related to liver injury of grade≥3 (NCI CTCAE v5.0), the dose is to be reduced to 600mg BID. It is at the discretion of the investigator whether or not to perform dose reduction based on how the subject is benefiting from study treatment. The subject should be discontinued from treatment if he/she re-experiences any adverse event related to liver injury of grade≥3 after dose reduction. |
| Placebo | Placebo comparator | Other: PlaceboComparator: Placebo Dosage and method of administration: Day 1: 1800mg, BID; Day 2 and thereafter: 600mg, TID, for a maximum of 14 days. Where the subject has experienced an adverse event related to liver injury of grade≥3 (NCI CTCAE v5.0), the dose is to be reduced to 600mg BID. It is at the discretion of the investigator whether or not to perform dose reduction based on how the subject is benefiting from study treatment. The subject should be discontinued from treatment if he/she re-experiences any adverse event related to liver injury of grade≥3 after dose reduction |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 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 Italian Ministry of Health guidelines and to the recommendations reported in Appendix 1 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/clinically diagnosed cases with all of the following etiological evidences:
- Note: Sputum specimen is preferred for RT-PCR test of 2019-nCov nucleic acid; the specific type of respiratory tract specimen (e.g., nasopharyngeal swabs, sputum, lower respiratory tract secretions) is to be selected based on the conditions of the local laboratory.
- The type of specimen and detection method for 2019-nCov should remain consistent for the same subject receiving study treatment.
Key exclusion criteria (11 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 |
|---|---|---|
| FavipiravirDosage and method of administration: Day 1: 1800mg, BID; Day 2 and thereafter: 600mg, TID, for a maximum of 14 days. Where the subject has experienced an adverse event related to liver injury of grade≥3 (NCI CTCAE v5.0), the dose is to be reduced to 600mg BID. It is at the discretion of the investigator whether or not to perform dose reduction based on how the subject is benefiting from study treatment. The subject should be discontinued from treatment if he/she re-experiences any adverse event related to liver injury of grade≥3 after dose reduction | Drug | Favipiravir |
| PlaceboDosage and method of administration: Day 1: 1800mg, BID; Day 2 and thereafter: 600mg, TID, for a maximum of 14 days. Where the subject has experienced an adverse event related to liver injury of grade≥3 (NCI CTCAE v5.0), the dose is to be reduced to 600mg BID. It is at the discretion of the investigator whether or not to perform dose reduction based on how the subject is benefiting from study treatment. The subject should be discontinued from treatment if he/she re-experiences any adverse event related to liver injury of grade≥3 after dose reduction | Other | Placebo |
Primary outcome
Time from randomization to clinical recovery
Time frame: 90 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 72 hours.
8 secondary outcomes
Time from randomization to negativity in RT-PCR nucleic acid test
Time frame: 28 days
Incidence of deterioration/aggravation of pneumonia
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
Time from randomization to relief of dyspnoea
Time frame: 28 days
Rate of auxiliary oxygen therapy
Time frame: 28 days
ICU admission rate
Time frame: 28 days
Mortality
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 8 Apr 2020.
- Individual participant dataSharing planned: Undecided
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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.
Giuliano Rizzardini, Md principal investigator
ASST Fatebenefratelli Sacco
1 site in 1 country: 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 Giuliano Rizzardini at 1 site in Italy.
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 15 inclusion and 11 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 8 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time from randomization to clinical recovery (time frame: 90 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 8 Apr 2020.