Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04529499
Recruitment Status : Active, not recruiting
First Posted : August 27, 2020
Last Update Posted : February 3, 2021
Sponsor:
Information provided by (Responsible Party):
Dr. Reddy's Laboratories Limited

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.


Condition or disease Intervention/treatment Phase
Covid19 Drug: AVIGAN Drug: Placebo Comparator Phase 3

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 780 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double Blind, Placebo Controlled Clinical Trial Evaluating the Efficacy and Safety of Favipiravir in Moderate to Severe COVID-19 Patients
Actual Study Start Date : August 20, 2020
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2021

Arm Intervention/treatment
Experimental: favipiravir + supportive care
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
Patients will be randomized to the favipiravir + supportive care group in a 1:1 ratio
Other Name: Favipiravir

Placebo Comparator: Placebo with Standard of Care
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
Patients will be randomized to the placebo + supportive care group in a 1:1 ratio
Other Name: Placebo




Primary Outcome Measures :
  1. Primary Efficacy Endpoint: Time to resolution of hypoxia (Stage I) [ Time Frame: 1-28 days ]
    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.


Secondary Outcome Measures :
  1. Time to alleviation of symptoms (Stage I) [ Time Frame: 1-28 days. ]
    Time (No. of days) from randomization to the earliest time when ALL COVID-19 associated symptoms (fever, chills, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms - specifically diarrhoea and vomiting, shortness of breath or dyspnoea) are scored by the Investigator/trained study personnel as either '0=absent' or 'mild =1' in assessments over a period of 24 hours, when assessed from baseline to Day 28 or discharge from hospital (if discharge happens earlier than Day 28).

  2. Percentage of patients with score of 0 = absent or mild = 1 (Stage I) [ Time Frame: 1-28 days. ]
    Percentage of patients with score of either '0=absent' or 'mild =1' over a period of 24 hours, for ALL COVID-19 associated symptoms, by Days 4, 7, 10, 14, 21 and 28 or discharge (if discharge happens earlier than one or more of the above-mentioned timepoints)

  3. Time to improvement in each of the symptoms (Stage I) [ Time Frame: 1-28 days. ]
    Time to improvement in EACH of the symptoms of fever, chills, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms- specifically diarrhoea and vomiting, shortness of breath or dyspnoea by at least 1 grade over baseline.

  4. Percentage of patients reporting a 'clinical relapse' (Stage I) [ Time Frame: 1-28 days. ]
    Percentage of patients reporting a clinical relapse of COVID-19 when assessed from day of discharge to 27 days after randomization (Day 28).

  5. Time to negative conversion of detectable SARS-CoV 2 (Stage I) [ Time Frame: 1-28 days. ]
    Time (no. of days) to negative conversion of detectable SARS-CoV 2 viral RNA in the RT-PCR assays of respiratory sample, from randomization.

  6. Percentage of patients showing negative conversion of detectable SARS-CoV 2 (Stage I) [ Time Frame: 1-28 days. ]
    Percentage of patients showing negative conversion of detectable SARS-CoV-2 viral RNA in the RT-PCR assays of respiratory sample on Days 5, 10 and 28 or discharge (if discharge happens earlier than one or more of the above-mentioned timepoints)

  7. Changes over time in patient's clinical status on the 10-point ordinal scale of clinical status (Stage I) [ Time Frame: 1-28 days. ]
    Changes over time in patient's clinical status on the 10-point ordinal scale used in the SOLIDARITY trial by WHO

  8. Changes over time in patient's clinical status on the 8-point ordinal scale of clinical status (Stage I) [ Time Frame: 1-28 days. ]
    Changes over time in patient's clinical status on the 8-point ordinal scale

  9. Changes over time in findings on chest X-ray (Stage I) [ Time Frame: 1-28 days. ]
    Changes over time in findings on chest X-ray

  10. Changes over time in the National Early Warning Score-2 (Stage I) [ Time Frame: 1-28 days. ]
    Changes over time in the National Early Warning Score-2 (NEWS-2)

  11. Percentage of patients requiring ICU management, high flow nasal oxygen and mechanical ventilation (Stage I) [ Time Frame: 1-28 days. ]

    Percentage of patients requiring, until Day 28 or discharge from hospital (if discharge happens earlier)

    1. Management in intensive care unit
    2. High Flow Nasal Oxygen or Non-invasive mechanical ventilation
    3. Invasive mechanical ventilation

  12. Time (no. of days) from randomization to ICU management, high flow nasal oxygen and mechanical ventilation (Stage I) [ Time Frame: 1-28 days. ]

    Time (no. of days) from randomization to:

    1. Management in intensive care unit
    2. High Flow Nasal Oxygen or Non-invasive mechanical ventilation
    3. Invasive mechanical ventilation over an assessment period from randomization until Day 28 or discharge from hospital (if discharge happens earlier)

  13. Duration (no. of days) the patient requires CU management, high flow nasal oxygen and mechanical ventilation (Stage I) [ Time Frame: 1-28 days. ]

    Duration (no. of days) the patient requires:

    1. Management in intensive care unit
    2. Oxygen supplementation
    3. High Flow Nasal Oxygen
    4. Non-invasive mechanical ventilation
    5. Invasive mechanical ventilation over an assessment period from randomization until Day 28 or discharge from hospital (if discharge happens earlier)

  14. Percentage of Patients dying (all cause and due to COVID-19) (Stage I) [ Time Frame: 1-28 days ]

    Percentage of Patients:

    1. dying from any cause
    2. dying from a COVID-19 associated complication over an assessment period from randomization until Day 28 or discharge from hospital (if discharge happens earlier)

  15. Percentage of 'clinical relapse' (Stage I + Stage II) [ Time Frame: 1 - 60 days ]

    Percentage of patients reporting a 'clinical relapse' of COVID-19 when assessed from day of discharge to 59 days after the day of start of study treatment (Day 60).

    Note: 'Clinical relapse' is defined as either the reappearance or worsening of severity (over the assessment on the day of discharge) of one or more of the above-mentioned COVID-19 associated symptoms, or the appearance of any of these symptoms (due to COVID 19 infection) for the first time after discharge.


  16. Incidence of treatment emergent adverse events (Stage I + Stage II) [ Time Frame: 1 - 60 days ]
    Number (and percentage) of patients reporting treatment emergent adverse events (TEAEs) (by MedDRA system organ class and preferred term)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female patients aged 21 to 80 years (both inclusive)
  2. 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
  3. Patients should be hospitalized
  4. 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

    1. 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
    2. blood oxygen saturation (SpO2) of 94% at rest on room air at sea level

    II. 'severe' COVID-19

    1. 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
    2. 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.

  5. Female patients of childbearing potential*

    1. must have a negative serum pregnancy test at screening
    2. 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.
    3. should commit to the use of TWO forms of study-acceptable contraception methods, including a barrier method (eg. diaphragm) along with one or more of the following methods of contraception for the duration of the treatment period and for 7 days after the last dose of study medication: i) hormonal methods [insertable, injectable, transdermal, or combination oral (estrogen+ progestin)], or ii) intrauterine contraceptive device

    Note: Female patients who are sexually abstinent or whose male sexual partner has undergone vasectomy at least three months prior to the start of study treatment in the trial may be enrolled at the Investigator's discretion, provided that they are counseled to remain sexually inactive for the duration of the study and understand the possible risks involved in getting pregnant during the study. Patients must also agree to use TWO forms of study-acceptable contraception methods should they become sexually active during the treatment period and for 7 days after the last dose of study medication.

    *Note: A female patient is considered of childbearing potential unless she is:

    1. postmenopausal for at least 12 months prior to study product administration, or
    2. without a uterus and/or both ovaries or has been surgically sterilized (i.e, tubal ligation or has a fallopian tube blocking coil) for at least 6 months prior to study product administration.
  6. Male patients should agree to abstain from sexual intercourse or to use double-barrier contraception (e.g. condom with spermicide) for the duration of the treatment period in the study and for at least 7 days after receiving the last dose of study medication. Male patients should also avoid semen donation or providing semen for in-vitro fertilization during the above-mentioned duration.
  7. Able and willing to provide informed consent
  8. Able to understand the trial requirements and comply with trial medications and assessments in the opinion of the Investigator
  9. Should not have received investigational treatment from participation in another clinical trial within 30 days prior to randomization in the current trial and agrees not to participate in other clinical studies during the entire study period

Exclusion Criteria:

  1. 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

  2. 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
  3. 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)

    Note: The above-mentioned exclusion criterion is not applicable in case of patients with history of human immunodeficiency virus infection or infective hepatitis in whom use of anti-viral drugs or interferons are prescribed for treatment of the underlying condition and who are currently receiving one or more of these medications (as maintenance treatment) at the time of randomization. The infection episode in question is a relapse of, or reinfection with SARS-CoV-2

  4. Patients suspected to have a complication of congestive cardiac failure based on Investigator's clinical judgement
  5. Patients with moderate and severe hepatic dysfunction equivalent to Grade B and Grade C in the Child-Pugh classification respectively
  6. Patients with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels > 5 times upper limit of normal (ULN) at screening evaluation
  7. Patients with renal impairment requiring dialysis
  8. Patients with serum uric acid higher than the ULN at screening evaluation
  9. Patients with history of hereditary xanthinuria
  10. Patients who have been diagnosed with xanthine urinary calculus
  11. Patients with a history of gout or patients who are currently being treated for gout
  12. Patients who are taking immunosuppressants
  13. Patients who were administered Favipiravir in the past 30 days
  14. Patients with known hypersensitivity reaction to Favipiravir

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04529499


Locations
Layout table for location information
Kuwait
Jaber Al-Ahmad Al-Sabah Hospital (South Surra)
Kuwait City, Kuwait, 47781
Mishref Field Hospital (Mishref)
Kuwait City, Kuwait, 90005
Sponsors and Collaborators
Dr. Reddy's Laboratories Limited
Investigators
Layout table for investigator information
Study Director: Sagar Munjal, MD, MS Vice President/Head of Clinical Development,Operations & Medical Affairs
Layout table for additonal information
Responsible Party: Dr. Reddy's Laboratories Limited
ClinicalTrials.gov Identifier: NCT04529499    
Other Study ID Numbers: CVD-04-CD-001
First Posted: August 27, 2020    Key Record Dates
Last Update Posted: February 3, 2021
Last Verified: September 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr. Reddy's Laboratories Limited:
AVIGAN
Favipiravir
COVID-19
Phase 3
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Favipiravir
Antiviral Agents
Anti-Infective Agents