Randomized Multicenter Study on the Efficacy and Safety of Favipiravir for Parenteral Administration Compared to Standard of Care in Hospitalized Patients With COVID-19

• ClinicalTrials.gov Identifier: NCT05185284
• Recruitment Status: Completed
• First Posted: January 11, 2022
• Last Update Posted: January 11, 2022
• Sponsor: Promomed, LLC
• Collaborator: Solyur Pharmaceuticals Group
• Information provided by (Responsible Party): Promomed, LLC

Tracking Information

• First Submitted Date: January 7, 2022
• First Posted Date: January 11, 2022
• Last Update Posted Date: January 11, 2022
• Actual Study Start Date: August 11, 2021
• Actual Primary Completion Date: December 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 7, 2022)

• Rate of Clinical Status Improvement [ Time Frame: By Visit 3, approximately 10 days ]
  Rate of clinical status improvement by WHO categorical ordinal scale of clinical status improvement by 2 or more categories by Day 10. WHO Ordinal Scale for Clinical Improvement (WHO-OSCI), 0 - uninfected (There are no clinical and virological signs of infection), 8 - dead, higher scores mean a worse outcome
• Time to Clinical Improvement [ Time Frame: 28 days ]
  Time (in days) to improvement in clinical status by WHO categorical ordinal scale of clinical status improvement

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: January 7, 2022)

• Rate of Clinical Status Improvement [ Time Frame: 14 days ]
  Rate of clinical status improvement by WHO categorical ordinal scale of clinical status improvement by 2 or more categories at Visits 2 (Day 5) and 4 (Day 14)
• Rate of Clinical Status Improvement [ Time Frame: 14 Days ]
  Percentage of patients with clinical status of 0 and 1 point according to the WHO categorical ordinal scale of clinical improvement on Days 5, 10 and 14.
• End of Fever on Days of study [ Time Frame: 14 Days ]
  Percentage of patients with fever disappearance (body temperature < 37,2 °C in 3 consecutive measurements without antipyretic medication) an Days 5, 10 and 14.
• Change in the Level of Lung Damage According to CT [ Time Frame: 14 Days ]
  Assessment of lung injury (degree of damage by "empirical" visual scale and % of patients) according to CT data comparing to baseline. The number of patients in whom by the end of therapy there was an improvement in the condition of the lungs (a decrease in the volume of the lesion according to CT)
• Rate of Viral Elimination [ Time Frame: 14 days ]
  Percentage of patients with SARS-CoV-2 elimination (negative test for SARS-CoV-2 by NAA method) on Days 5, 10, and 14.
• Rate of Transfer to the Intensive Care Unit [ Time Frame: 28 days ]
  Percentage of patients transferred to intensive care unit
• Rate of the Use of Non-invasive Lung Ventilation [ Time Frame: 28 Days ]
  Percentage of cases with non-invasive lung ventilation
• Rate of the Use of Mechanical Ventilation [ Time Frame: 28 Days ]
  Percentage of cases with mechanical lung ventilation (% of patients)
• Mortality [ Time Frame: 28 Days ]
  Incidence of fatal cases (% of patients)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Randomized Multicenter Study on the Efficacy and Safety of Favipiravir for Parenteral Administration Compared to Standard of Care in Hospitalized Patients With COVID-19
• Official Title: Open-label Randomized Multicenter Comparative Study on the Efficacy and Safety of AREPLIVIR® (Favipiravir) for Parenteral Administration (PROMOMED RUS LLC, Russia) in Hospitalized Patients With COVID-19
• Brief Summary: This is open-labe randomized multicenter comparative Phase III study conducted in 7 medical facilities. The objective of the study is to assess the efficacy and safety of Favipiravir for parenteral administration compared with the Standard of care (SOC) in hospitalized patients with moderate COVID-19 pneumonia.
• Detailed Description: Upon signing the informed consent form and screening, 217 eligible patients hospitalized with COVID-19 pneumonia were randomized at a 1:1 ratio to receive either Favipiravir intravenously by drip infusion for 2 hours 1600 mg twice a day (BID) on Day 1 followed by 800 mg BID on Days 2-14 (1600/800 mg), or SOC. The course of treatment by Favipiravir is 10 days.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Drug: Favipiravir
  400 mg, lyophilizate for preparation of concentrate for solution for infusion
  Other Name: Areplivir
• Drug: Favipiravir
  200 mg coated tablets
• Drug: Remdesivir
  100 mg, lyophilizate for preparation of concentrate for solution for infusion

Study Arms

• Experimental: Favipiravir (Areplivir)
  Arm 1 (n=106) receives the study drug Areplivir for parenteral administration as follows: Day 1 1600 mg 2 times a day, Day 2-10 800 mg 2 times a day. Administration will be done intravenously by drip infusion for 2 hours. The course of treatment is 10 days. The test drug is administered in hospital setting under supervision of a clinical investigator. The test drug is not handed over to the patient.
  Intervention: Drug: Favipiravir
• Active Comparator: Standard of care

  Arm 2 (n=108) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health by decision of the investigator and taking into account the availability of drugs at the study site. Might include Favipiravir tab, Remdesivir or other recommended schemes.

  Standard therapy is administered in hospital setting. Discharge of patients from a hospital is carried out in accordance with the local practice of the study site in compliance with the current sanitary and epidemiological regime.

  Interventions:

  • Drug: Favipiravir
  • Drug: Remdesivir

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 7, 2022): 217
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: December 30, 2021
• Actual Primary Completion Date: December 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Availability of the Informed Consent Form of the Patient Information Leaflet (PIL) signed and dated by patient.
2. Men and women aged 18 to 80 years inclusive at the time of signing the Informed Consent Form in PIL.
3. Confirmed case of COVID-19 at the time of screening based on SARS-CoV-2 RNA test using nucleic acid amplification (NAA) method. It is acceptable to include a patient with a presumptive COVID-19 diagnosis prior to receiving the results of SARS-CoV-2 RNA test made at the screening stage.
4. Hospital admission due to COVID-19.

5. Moderate severity infection with SARS-CoV-2:

   • Clinical signs:
   • Mandatory: CT pattern typical of a viral lesion (lesion volume is minimal or moderate; CT 1-2).
   • Additional (at least 1 of the following criteria):
   • body temperature > 38 °C;
   • RR > 22/min;
   • shortness of breath on exertion;
   • SpO2 < 95%;
   • Serum CRP > 10 mg/L.
6. Patient's consent to use reliable contraceptive methods throughout the study and within 1 month for women and 3 months for men after its completion. Reliable means of contraception are: sexual abstinence, use of condom in combination with spermicide.

For men (optional): Consent to avoid sexual contact with pregnant women for the duration of the study and for 3 months after its completion.

Women incapable of childbearing may also participate in the study (with past history of: hysterectomy, tubal ligation, infertility, menopause for more than 2 years), as well as men with infertility or a history of vasectomy.

Exclusion Criteria:

1. Hypersensitivity to favipiravir, remdesivir and/or other components of the study drug.
2. Impossibility of CT procedure (for example, gypsum dressing or metal structures in the field of imaging).
3. History of vaccination against COVID-19.
4. History of presumptive or confirmed COVID-19 case of moderate, severe and extremely severe course of the disease.
5. Use of favipiravir or remdesivir within 10 days prior to screening.
6. The need to use drugs from the list of prohibited therapy.
7. Meeting the criteria for severe and extremely severe course of the disease.
8. Need for treatment in the intensive care unit.
9. Impaired liver function (AST and/or ALT ≥ 2 UNL and/or total bilirubin ≥ 1.5 UNL) at the time of screening.
10. Renal impairment (GFR < 60 ml/min) at the time of screening.
11. History of gout.
12. Positive testing for HIV, syphilis, hepatitis B and/or C.
13. Chronic heart failure FC III-IV according to New York Heart Association (NYHA) functional classification (see Appendix 2).
14. Malignancies in the past medical history.
15. Alcohol, pharmacological and/or drug addiction in the past medical history and/or at the time of screening.
16. Schizophrenia, schizoaffective disorder, bipolar disorder, or other history of mental pathology or suspicion of their presence at the time of screening.
17. Severe, decompensated or unstable somatic diseases (any disease or condition that threaten the patient's life or impair the patient's prognosis, and also make it impossible for him/her to participate in the clinical study).
18. Any history data that the investigating physician believes could lead to complication in the interpretation of the study results or create an additional risk to the patient as a result of his/her participation in the study.
19. Patient's unwillingness or inability to comply with procedures of the Study Protocol (in the opinion of physician investigator).
20. Pregnant or nursing women or women planning pregnancy.
21. Participation in another clinical study for 3 months prior to inclusion in the study.
22. Other conditions that, according to the physician investigator, prevent the patient from being included in the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Russian Federation

Administrative Information

• NCT Number: NCT05185284
• Other Study ID Numbers: FAV-052021
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: January 2022

• Current Responsible Party: Promomed, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Promomed, LLC
• Original Study Sponsor: Same as current
• Collaborators: Solyur Pharmaceuticals Group

Investigators

• Principal Investigator: Dmitriy Pushkar, MD, Academic; Moscow State Clinical Hospital №50

• PRS Account: Promomed, LLC
• Verification Date: January 2022