Clinical Trial Evaluating the Efficacy and Safety of Favipiravir in Moderate to Severe COVID-19 Patients

NCT04529499 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: CVD-04-CD-001
• Study Type: interventional
• Target: 353
• Locations: 1 country
• Sites: 2

Brief Summary

This is a prospective, interventional, multi-centre, phase III, randomized, double blind, placebo-controlled, parallel design trial to evaluate the efficacy, safety and tolerability of favipiravir as adjunct ('add on') to supportive care, in comparison to placebo with supportive care, in the acute treatment of patients who have tested positive for SARS-CoV-2 and presenting with moderate to severe COVID-19. This study will be conducted in two parts; Stage I - Main study and Stage II - Extended Follow up.

Conditions

Covid19

Keywords

AVIGAN; Favipiravir; COVID-19; Phase 3

Outcome Measures

Primary Outcomes (1)

• Primary Efficacy Endpoint: Time to Resolution of Hypoxia (Stage I)

  This endpoint will be considered to have been met when the patient has attained a score of 4 or lower on the 10-point ordinal scale of clinical status used by WHO in the SOLIDARITY trial (maintaining a blood oxygen saturation of ≥ 95% at rest on room air at sea level) when evaluated over a period of 24 hours.

  1-28 days

Secondary Outcomes (1)

• Percentage of Patients Dying (All Cause (Stage I)

  1-28 days

Study Arms (2)

favipiravir + supportive care

EXPERIMENTAL

Frequency: Twice daily (morning and evening) Dosage Form: Tablets. Tablet Strength 200 mg. Dosage: 1,800 mg BID on Day 1 + 800 mg BID for next 9 days (maximum). On Day 1, the second dose will be administered with at least a 4-hour interval from administration of the first dose.

Drug: AVIGAN

Placebo with Standard of Care

PLACEBO COMPARATOR

Frequency: Twice daily (morning and evening) Dosage Form: Tablets Dosage: 9 tablets for BID on Day 1 + 4 tablets BID for next 9 days (maximum). On Day 1, the second dose will be administered with at least a 4-hour interval from administration of the first dose.

Drug: Placebo Comparator

Interventions

AVIGAN DRUG

Patients will be randomized to the favipiravir + supportive care group in a 1:1 ratio

Also known as: Favipiravir

favipiravir + supportive care

Placebo Comparator DRUG

Patients will be randomized to the placebo + supportive care group in a 1:1 ratio

Also known as: Placebo

Placebo with Standard of Care

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients aged 21 to 80 years (both inclusive)
• Patients who have tested positive for SARS-CoV-2 by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) assay using a respiratory tract sample (either nasopharyngeal swab OR oropharyngeal swab OR nasal aspirate OR tracheobronchial aspirate) collected within 72 hours of randomization
• Patients should be hospitalized
• Patients having moderate or severe COVID-19\* with a score of \> 4 on the 10-point ordinal scale of clinical status used by WHO in the SOLIDARITY trial at baseline assessment \[i.e., patients with blood oxygen saturation (SpO2) \<95% at rest on room air at sea level and requiring supplemental oxygen\].
• \*Note: This includes patients clinically assigned as:
• I. 'moderate' COVID-19
• symptoms which could include fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms or shortness of breath with exertion and/or clinical signs, such as respiratory rate ≥20 breaths per minute or heart rate ≥90 beats per minute AND
• blood oxygen saturation (SpO2) of 94% at rest on room air at sea level
• II. 'severe' COVID-19
• symptoms which could include any symptom of moderate illness or shortness of breath at rest, or respiratory distress and/or clinical signs, such as respiratory rate ≥30 per minute or heart rate ≥125 per minute AND
• blood oxygen saturation (SpO2) ≤93% on room air at sea level or PaO2/FiO2 \<300\*
• The above-mentioned definitions of COVID-19 severity are adapted from the FDA Guidance document "COVID-19: Developing Drugs and Biological Products for Treatment or Prevention - Guidance for Industry Final Document" dated May 2020.
• Female patients of childbearing potential\*
• must have a negative serum pregnancy test at screening
• should not be lactating; and not planning to become pregnant/breast feed during the treatment period and for 7 days after the last dose of study medication.

You may not qualify if:

• Critically ill patients, defined as those who are candidates for endotracheal intubation and mechanical ventilation, oxygen delivered by high- flow nasal cannula, (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20 L/min with fraction of delivered oxygen ≥0.5), non-invasive positive pressure ventilation, Extracorporeal Membrane Oxygenation (ECMO) , or clinical diagnosis of respiratory failure (i.e., clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation) and those with shock (defined by systolic blood pressure (BP) \<90 mm Hg, or diastolic BP \<60 mm Hg or requiring vasopressors) or multi-organ dysfunction/failure, at baseline
• Note: The above-mentioned definition of 'critically ill' COVID-19 patients is as defined in the FDA Guidance document "COVID-19: Developing Drugs and Biological Products for Treatment or Prevention - Guidance for Industry Final Document" dated May 2020
• Patients in whom the first onset of symptoms/signs suggestive of COVID-19 illness was observed \>10 days earlier to the baseline assessment and randomization
• Patients who have used interferon beta 1-a (IFN-β-1a) preparations or drugs with reported anti-viral action against SARS-CoV-2 (hydroxychloroquine sulfate, chloroquine phosphate, lopinavir-ritonavir combination drugs, ciclesonide, nafamostat mesylate, camostat mesylate) within 8 days after development of fever (≥37.5°C)
• Patients suspected to have a complication of congestive cardiac failure based on Investigator's clinical judgement
• Patients with moderate and severe hepatic dysfunction equivalent to Grade B and Grade C in the Child-Pugh classification respectively
• Patients with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels \> 5 times upper limit of normal (ULN) at screening evaluation
• Patients with renal impairment requiring dialysis
• Patients with serum uric acid higher than the ULN at screening evaluation
• Patients with history of hereditary xanthinuria
• Patients who have been diagnosed with xanthine urinary calculus
• Patients with a history of gout or patients who are currently being treated for gout
• Patients who are taking immunosuppressants
• Patients who were administered Favipiravir in the past 30 days
• Patients with known hypersensitivity reaction to Favipiravir

Sponsors & Collaborators

• Dr. Reddy's Laboratories Limited: lead

Study Sites (2)

Jaber Al-Ahmad Al-Sabah Hospital (South Surra)

Kuwait City, 47781, Kuwait

Location

Mishref Field Hospital (Mishref)

Kuwait City, 90005, Kuwait

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

Results Point of Contact

• Title: Dr. Srinivas Shenoy B.,
• Organization: Dr Reddy's Laboratories Ltd.

srinivassshenoyb@drreddys.com

49002900

Study Officials

• Sagar Munjal, MD, MS

  Dr Reddy's Laboratories, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a prospective, interventional, multi-centre, phase III, randomized, double blind, placebo-controlled, parallel design trial to evaluate the efficacy, safety and tolerability of favipiravir as adjunct ('add on') to supportive care, in comparison to placebo with supportive care, in the acute treatment of patients who have tested positive for SARS-CoV-2 and presenting with moderate to severe COVID-19.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 780 patients are randomized into two treatment groups at a 1:1 ratio, so as to have approximately 390 patients in favipiravir + supportive care group and 390 patients in placebo + supportive care group.

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: August 27, 2020
• Study Start: August 22, 2020
• Primary Completion: January 22, 2021
• Study Completion: January 27, 2021
• Last Updated: March 21, 2022
• Results First Posted: March 21, 2022

Record last verified: 2022-03

Locations

KU (2)