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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05185284
• Other study ID #: FAV-052021
• Status: Completed
• Phase: Phase 3
• Start date: August 11, 2021
• Est. completion date: December 30, 2021

Study information

• Verified date: January 2022
• Source: Promomed, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 217
• Est. completion date: December 30, 2021
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

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

Locations

Country	Name	City	State
Russian Federation	Regional budgetary health care institution "Ivanovo Clinical Hospital named after Kuvaevs"	Ivanovo
Russian Federation	State Budgetary Institution of Healthcare of the City of Moscow "City Clinical Hospital No. 24 of the Department of Healthcare of the City of Moscow"	Moscow
Russian Federation	State Clinical Hospital ?50	Moscow
Russian Federation	Regional Clinic Hospital of Ryazan	Ryazan'
Russian Federation	Medical institute Ogarev Mordovia State university	Saransk
Russian Federation	Smolensk clinical hospital ?1	Smolensk

Sponsors (2)

Lead Sponsor	Collaborator
Promomed, LLC	Solyur Pharmaceuticals Group

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Clinical Status Improvement	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	By Visit 3, approximately 10 days
Primary	Time to Clinical Improvement	Time (in days) to improvement in clinical status by WHO categorical ordinal scale of clinical status improvement	28 days
Secondary	Rate of Clinical Status Improvement	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)	14 days
Secondary	Rate of Clinical Status Improvement	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.	14 Days
Secondary	End of Fever on Days of study	Percentage of patients with fever disappearance (body temperature < 37,2 °C in 3 consecutive measurements without antipyretic medication) an Days 5, 10 and 14.	14 Days
Secondary	Change in the Level of Lung Damage According to CT	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)	14 Days
Secondary	Rate of Viral Elimination	Percentage of patients with SARS-CoV-2 elimination (negative test for SARS-CoV-2 by NAA method) on Days 5, 10, and 14.	14 days
Secondary	Rate of Transfer to the Intensive Care Unit	Percentage of patients transferred to intensive care unit	28 days
Secondary	Rate of the Use of Non-invasive Lung Ventilation	Percentage of cases with non-invasive lung ventilation	28 Days
Secondary	Rate of the Use of Mechanical Ventilation	Percentage of cases with mechanical lung ventilation (% of patients)	28 Days
Secondary	Mortality	Incidence of fatal cases (% of patients)	28 Days