Clinical trial NCT05185284: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: SARS-CoV-2
Areplivir
2019-nCoV
Favipiravir
Pneumonia
Coronavirus Infections
Lead sponsor: Promomed, LLC
Sponsor class: OTHER
Collaborators: name: Solyur Pharmaceuticals Group
First posted: 2022-01-11
Enrollment: 217
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Rate of Clinical Status Improvement
timeFrame: By Visit 3, approximately 10 days
measure: Time to Clinical Improvement
timeFrame: 28 days
Secondary outcomes:
measure: Rate of Clinical Status Improvement
timeFrame: 14 days
measure: Rate of Clinical Status Improvement
timeFrame: 14 Days
measure: End of Fever on Days of study
timeFrame: 14 Days
measure: Change in the Level of Lung Damage According to CT
timeFrame: 14 Days
measure: Rate of Viral Elimination
timeFrame: 14 days
measure: Rate of Transfer to the Intensive Care Unit
timeFrame: 28 days
measure: Rate of the Use of Non-invasive Lung Ventilation
timeFrame: 28 Days
measure: Rate of the Use of Mechanical Ventilation
timeFrame: 28 Days
measure: Mortality
timeFrame: 28 Days
Other outcomes:
Locations:
city: Ivanovo
country: Russian Federation
facility: Regional budgetary health care institution "Ivanovo Clinical Hospital named after Kuvaevs"
city: Moscow
country: Russian Federation
facility: 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"
city: Moscow
country: Russian Federation
facility: State Clinical Hospital №50
city: Ryazan'
country: Russian Federation
facility: Regional Clinic Hospital of Ryazan
city: Saransk
country: Russian Federation
facility: Medical institute Ogarev Mordovia State university
city: Smolensk
country: Russian Federation
facility: Smolensk clinical hospital №1
Study officials:
affiliation: Moscow State Clinical Hospital №50
name: Dmitriy Pushkar, MD, Academic
role: PRINCIPAL_INVESTIGATOR
References: