Page Nct des essais cliniques

Summary
EudraCT Number:2022-001387-10
Sponsor's Protocol Code Number:220301
National Competent Authority:Portugal - INFARMED
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-11-16
Trial results
A. Protocol Information
A.1Member State ConcernedPortugal - INFARMED
A.2EudraCT number2022-001387-10
A.3Full title of the trial
A Phase 3, Multicenter, Prospective, Placebo-Controlled, Randomized, Double-Blind Study to Assess the Efficacy and Safety of Favipiravir in Non-critical Hospitalized Patients with COVID-19 Pneumonia (PROVIR)
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
A Phase 3 blinded study to assess the efficacy and safety of Favipiravir vs placebo in Non-critical Hospitalized Patients with COVID-19 Pneumonia (PROVIR)
A.3.2Name or abbreviated title of the trial where available
PROVIR
A.4.1Sponsor's protocol code number220301
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorTECNIMEDE, Sociedade Técnico-Medicinal, S.A.
B.1.3.4CountryPortugal
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportTECNIMEDE, Sociedade Técnico-Medicinal, S.A.
B.4.2CountryPortugal
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationTECNIMEDE, Sociedade Técnico-Medicinal, S.A.
B.5.2Functional name of contact pointMedical Department Dev. Projects
B.5.3 Address:
B.5.3.1Street AddressRua da Tapada Grande, n.º 2, Abrunheira
B.5.3.2Town/ citySintra
B.5.3.3Post code2710-089
B.5.3.4CountryPortugal
B.5.4Telephone number+3512104 14 18 7
B.5.6E-maildmed.ct@tecnimede.pt
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Favipiravir Tablets 200 mg - Fabiflu
D.2.1.1.2Name of the Marketing Authorisation holderGLENMARK PHARMACEUTICALS LIMITED - India
D.2.1.2Country which granted the Marketing AuthorisationIndia
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameFavipiravir
D.3.4Pharmaceutical form Tablet
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNFAVIPIRAVIR
D.3.9.2Current sponsor code259793-96-9
D.3.9.4EV Substance CodeSUB194303
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number200
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboTablet
D.8.4Route of administration of the placeboOral use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Coronavirus disease 2019 (COVID-19 pneumonia)
E.1.1.1Medical condition in easily understood language
Coronavirus disease 2019 (COVID-19 pneumonia)
E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 25.1
E.1.2Level LLT
E.1.2Classification code 10066740
E.1.2Term Acute respiratory tract infection
E.1.2System Organ Class 100000004862
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
• To assess the clinical efficacy of favipiravir plus standard of care (SOC) compared to placebo plus SOC by reduction in clinical deterioration.
E.2.2Secondary objectives of the trial
• To assess the impact of favipiravir in preventing COVID-19 disease progression.
• To assess the impact of favipiravir on the duration of hospitalization, intensive care unit (ICU) admission, duration of stay in the ICU, mortality, and other healthcare resource use.
• To assess the virologic efficacy of favipiravir.
• To assess the safety and tolerability of favipiravir.
E.2.3Trial contains a sub-study Yes
E.2.3.1Full title, date and version of each sub-study and their related objectives
To characterize the pharmacokinetic (PK) profile of favipiravir in plasma.
E.3Principal inclusion criteria
1. Adults aged >= 18 years.
2. Patient understands and agrees to comply with planned study procedures and provides informed consent prior to undergoing any study procedures.
3. Hospitalized for symptoms associated with non-critical COVID-19 pneumonia with an interval between symptoms onset and randomization preferably until 4 days but no longer than 10 days.
4. Virologic confirmation of SARS-CoV-2 infection within 72 hours of randomization as determined by a valid test on respiratory tract specimens.
5. Category 4 or 5 on the WHO 10-point Ordinal Scale for Clinical Progression at time of randomization (hospitalized, with no oxygen therapy, or with oxygen by mask or nasal prongs).
6. Radiological evidence of lung infiltrates consistent with COVID-19 related pneumonia.
7. Women of childbearing potential must have a negative serum pregnancy test.
8. Female and male patients of childbearing potential must agree to use highly effective methods of birth control during their participation in the study and for 7 days after the last administration of study drug.
9. Able to swallow oral medication.
E.4Principal exclusion criteria
1. Hospitalized in the ICU at time of informed consent.
2. Need for advanced ventilatory or clinical support such as non-invasive ventilation (specifically for COVID-19 or within less than 6 months for other pathologies/comorbidities), high flow oxygen therapy, mechanical ventilation, dialysis, or ECMO.
3. History of hypersensitivity to an antiviral nucleoside-analog drug targeting a viral RNA polymerase.
4. Known hypersensitivity to favipiravir or any of its components.
5. Treatment with chemotherapy and/or radiotherapy within 6 months prior to patient randomization.
6. Known history of gout or under treatment for gout or hyperuricemia, hereditary xanthinuria, or hypouricemia or xanthine calculi of the urinary tract.
7. Severe hepatic impairment (Child-Pugh class C, aspartate transaminase [AST] or alanine aminotransferase [ALT] >3 times the upper limit) or end-stage liver disease.
8. Known chronic renal impairment/failure (estimated glomerular filtration rate [eGFR] <30 mL/min or requiring hemodialysis or continuous ambulatory peritoneal dialysis [CAPD]).
9. Severe chronic cardiovascular disorders (defined for the study as prolonged QT (defined as QTcF≥450 msec for men and as QTcF ≥470 msec for women), left ventricular ejection fraction <30%, chronic heart failure (NYHA class IV), active coronary artery disease (CAD) during the last 3 months, clinically significant arrhythmias, uncontrolled blood pressure).
10. Concurrent participation in another clinical trial.
11. Use of monocloncal antibodies or antivirals for COVID-19 treatment (eg, remdesivir, molnupiravir, nirmatrelvir/ritonavir) or for other concurrent infection (eg, oseltamivir for an influenza virus, lopinavir/ritonavir for Human Immunodeficiency Virus [HIV], etc.)
12. Taking corticosteroids (except topical or inhaled preparations or oral preparations equivalent to or less than 10 mg of oral prednisone), immunosuppressive or immunomodulatory drugs (eg, immunosuppressants, anticancer drugs, interleukins, interleukin antagonists or interleukin receptor blockers) or any monoclonal antibody treatment indicated for other medical conditions prior to SARS-CoV-2 infection.
Note: Treatment of study patients following institutional COVID-19 treatment policies or guidelines, including the use of corticosteroids is permitted.
13. Female patients who are pregnant or breastfeeding.
14. Any condition that, in the opinion of the Investigator, is likely to interfere with the safety and efficacy of the study treatment or puts the patient at unacceptably high risk from the study.
15. Any concomitant medication that could have any potential clinically significant drug interaction with the study treatment.
E.5 End points
E.5.1Primary end point(s)
Proportion of patients hospitalized requiring non-invasive ventilation or high flow oxygen, mechanical ventilation, dialysis, ECMO or who are dead at any time from randomization up to Day 15.
E.5.1.1Timepoint(s) of evaluation of this end point
Primary endpoint will be evaluated up to day 15.
E.5.2Secondary end point(s)
Efficacy

To assess the impact of favipiravir in preventing COVID-19 disease progression:
• Proportion of patients hospitalized requiring non-invasive ventilation, mechanical ventilation, ECMO, dialysis or who are dead at Day 29 and at Day 90.
• Clinical status as assessed with the WHO 10-point Ordinal Scale for Clinical -Progression at Day 8, Day 15 and Day 90.
• Change in clinical status as assessed with the WHO 10-point Ordinal Scale for Clinical Progression at Day 8, Day 15 and Day 90 relative to Baseline.
• Time to change in 1 or in 2 levels/points of the National Early Warning Score 2 (NEWS2) scoring system up to Day 29.

To assess the impact of favipiravir on the duration of hospitalization, ICU admission, duration of stay in the ICU, mortality, and other healthcare resource use:
• Duration of hospitalization (days) up to and including Day 90.
• Proportion of patients in ICU at Day 8, Day 15, Day 29 and Day 90; Duration of stay in the ICU up to and including Day 90).
• Overall survival up to and including Day 90.
• Proportion of patients requiring any supplemental oxygen therapy at Day 8, Day 15, Day 29 and Day 90.
•Duration of oxygen therapy (days) up to Day 90.
•Proportion of patients requiring non-invasive ventilation or high flow oxygen, mechanical ventilation, dialysis or ECMO during hospitalization.
• Duration of non-invasive ventilation or high flow oxygen (days) up to Day 90.
• Proportion of patients requiring invasive mechanical ventilation or ECMO during hospitalization.
• Duration of invasive mechanical ventilation or ECMO (days) up to Day 90.
• Proportion of patients requiring dialysis during hospitalization.
• Duration of dialysis (days) up to Day 90.

To assess the virologic efficacy of favipiravir.
• Change from Baseline in quantitative SARS-CoV-2 viral load by RT-PCR at Days 3, 5, 8, 10, 15, and 29.
• Proportion of patients with viral clearance at Day 8, Day 10 or Day of Discharge, Day 15, and Day 29.


Safety

To assess the safety and tolerability of favipiravir:
• Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) including deaths,and premature discontinuations of study drug up to Day 90/End of Follow-up.
• Clinically significant changes in laboratory parameters (hematology, chemistry, hepatic, coagulation, urinalysis).
• Clinically significant changes in electrocardiogram (ECG) results.
• Clinically significant changes in vital signs.
• Clinically significant changes in physical examination results.
E.5.2.1Timepoint(s) of evaluation of this end point
Secondary endpoints will be evaluated on days 3, 5, 8, 10, 15, 29 and 90, depending on the endpoint
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy No
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo Yes
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned5
E.8.5The trial involves multiple Member States No
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
The study will end when the last subject has completed the final assessment (Day 90/End of Follow-up visit).
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years1
E.8.9.1In the Member State concerned months0
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years1
E.8.9.2In all countries concerned by the trial months0
E.8.9.2In all countries concerned by the trial days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 144
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 336
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state480
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Subjects will be treated according to standard of care as defined per local written policies or guidelines.
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-12-29
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-11-25
P. End of Trial
P.End of Trial StatusOngoing
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