Study of Favipiravir Compared to Standard of Care in Hospitalized Patients With COVID-19

Open-label Randomized Multicenter Comparative Study on the Efficacy and Safety of Areplivir Film-coated Tablets (PROMOMED RUS LLC, Russia) in Patients Hospitalized With COVID-19

This is open-labe randomized multicenter comparative Phase III study conducted in 5 medical facilities. The objective of the study is to assess the efficacy and safety of Favipiravir compared with the Standard of care (SOC) in hospitalized patients with moderate COVID-19 pneumonia.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Favipiravir; Drug: Standard of care

Detailed Description

Upon signing the informed consent form and screening, 200 eligible patients with polymerase chain reaction (PCR) confirmed COVID-19 are randomized at a 1:1 ratio to receive either Favipiravir 1600 mg twice a day (BID) on Day 1 followed by 600 mg BID on Days 2-14 (1600/600 mg), or SOC. The course of treatment by Favipiravir is 14 days.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • State Clinical Hospital №50
  • Ryazan', Russian Federation
    • Regional Clinic Hospital of Ryazan
  • Saint Petersburg, Russian Federation
    • City Hospital N40 of Kurortny District
  • Saransk, Russian Federation
    • Medical institute Ogarev Mordovia State university
  • Smolensk, Russian Federation
    • Smolensk clinical hospital №1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signing and dating of the Informed Consent Form of the Patient Information Leaflet (PIL) by patients.
2. Men and women aged 18 to 80 years inclusive at the time of signing the Informed Consent Form in PIL.
3. No difficulty with oral medication (e.g. swallowing disorder).

4. Patient diagnosed with "Coronavirus infection caused by SARS-CoV-2 (confirmed)1, moderate severity form*" established in accordance with the Interim Guidelines of the Russian Ministry of Health for the prevention, diagnosis and treatment of a new coronavirus infection (COVID-19), (revision 6 of 28.04.2020).

   *Moderate severity form: fever above 38 °C, BR above 22/min, dyspnea during exercise, pneumonia (confirmed by lung CT), SpO2 < 95%, C reactive protein (CRP) serum level above 10 mg/l.

5. Patient should be hospitalized no more than 48 hours before the start of the study therapy.
6. Positive PCR result for presence of SARS-CoV-2 RNA at screening phase (results obtained within 7 days prior to screening are appropriate).
7. 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. Persons eligible for participation in the study: - Women who have a negative pregnancy test and use the following contraceptives: barrier method (condom or occlusive cap (diaphragm or cervical/vaulted cap)) or double barrier method of contraception (condom or occlusive cap (diaphragm or cervical/vaulted cap) plus spermicide (foam/gel/film/cream/suppository)). Women incapable of childbearing may also participate in the study (with past history of: hysterectomy, tubal ligation, infertility, menopause more than 1 year) or men with preserved reproductive function who use barrier contraceptives, as well as men with infertility or vasectomy in the past medical history.

Exclusion Criteria:

1. Hypersensitivity to favipiravir 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. The need to use drugs from the list of prohibited therapy.
4. Need for treatment in the intensive care unit.
5. Impaired liver function (AST and/or ALT ≥ 2 UNL and/or total bilirubin ≥ 1.5 UNL) at the time of screening.
6. Impaired kidney function (creatinine clearance according to Cockcroft-Gault formula less than 45 ml/min) at the time of screening.
7. Positive testing for HIV, syphilis, hepatitis B and/or C.
8. Chronic heart failure FC III-IV according to New York Heart Association (NYHA) functional classification.
9. Malabsorption syndrome or other clinically significant gastrointestinal disease that may affect absorption of the study drug (non-correctable vomiting, diarrhea, ulcerative colitis, and others).
10. Malignancies in the past medical history.
11. Alcohol, pharmacological and/or drug addiction in the past medical history and/or at the time of screening.
12. Schizophrenia, schizoaffective disorder, bipolar disorder, or other history of mental pathology or suspicion of their presence at the time of screening.
13. 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).
14. 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.
15. Patient's unwillingness or inability to comply with procedures of the Study Protocol (in the opinion of physician investigator).
16. Pregnant or nursing women or women planning pregnancy.
17. Participation in another clinical study for 3 months prior to inclusion in the study.
18. Other conditions that, according to the physician investigator, prevent the patient from being included in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Favipiravir (Areplivir); Arm 1 (n=100) receives the study drug Areplivir film-coated tablets: on day 1 of therapy - 1600 mg (8 tablets) 2 times a day; on days 2-14 of treatment - 600 mg (3 tablets) 2 times a day. The drug is taken orally every 12 hours, swallowing whole tablet without chewing and washing down with a glass of water. The course of treatment is 14 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.	Drug: Favipiravir; 200 mg coated tablets; Other Names: AREPLIVIR
Active Comparator: Standard of care; Arm 2 (n=100) 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 (but not Favipiravir) by decision of the investigator and taking into account the availability of drugs at the study site. Might include hydroxychloroquine (with or without azithromycin), chloroquine, lopinavir/ritonavir 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.	Drug: Standard of care; Drug: Standard of Care Standard of Care will be prescribed in accordance with the recommended treatment regimens presented in the Russian guidelines for the prevention, diagnosis and treatment of COVID-19 according to the decision of the Investigator. Other Name: Hydroxychloroquine, chloroquine, lopinavir/ritonavir, etc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Clinical Status Improvement	Rate of clinical status improvement by 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
Time to Clinical Improvement	Time (in days) to improvement in clinical status by WHO categorical ordinal scale of clinical status improvement.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Viral Elimination by Day 10	Percentage of patients with elimination (clearance) of COVID-19 according to PCR data by day 10 (negative PCR results).	10 days
Time Before the End of Fever	Time (in days) before the end of fever (body temperature < 37.2 ° C for 3 consecutive days without antipyretic medication).	28 days
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)	Days 15, 21, 28
Rate of Transfer to the Intensive Care Unit	Percentage of patients transferred to intensive care unit (% of patients).	28 Days
Rate of the Use of Non-invasive Lung Ventilation	Percentage of cases with non-invasive lung ventilation (% of patients).	28 Days
Rate of the Use of Mechanical Ventilation	Percentage of cases with mechanical lung ventilation (% of patients)	28 Days
Mortality	Incidence of fatal cases (% of patients)	28 Days

Collaborators and Investigators

• Sponsor: Promomed, LLC
• Investigators: Principal Investigator: Dmitriy Pushkar, Moscow State Clinical Hospital №50

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2020
• Primary Completion (Actual): August 10, 2020
• Study Completion (Actual): August 20, 2020

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: September 4, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Favipiravir; 2019-nCoV; Areplivir
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiviral Agents; Favipiravir
• Other Study ID Numbers: FAV052020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No