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

NCT04434248 | Unknown Phase 2 DMC

• 1 other identifier: COVID-FPR-01
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 22

Brief Summary

The study is Phase II/III and consists of pilot and pivotal stages. The objective of the pilot stage is to conduct a preliminary assessment of the efficacy and safety of Favipiravir, and to select the optimal dosing regimen to study during the pivotal stage. The objective of the pivotal stage is to assess the efficacy and safety of Favipiravir compared with the Standard of care (SOC) in hospitalized patients with moderate to severe COVID-19 pneumonia.

Conditions

COVID-19

Keywords

SARS-CoV-2; 2019-nCoV

Outcome Measures

Primary Outcomes (3)

• Rate of viral elimination by Day 10 [pilot stage, dose selection]

  Percent of patients with undetectable SARS-CoV-2 RNA level on Day 10

  10 Days

• Time to viral elimination [pivotal stage]

  Median time to reach undetectable SARS-CoV-2 RNA level

  28 Days

• Time to clinical improvement [pivotal stage]

  Median time reach clinical improvement (2 points of the Ordinal Scale for Clinical Improvement) or discharge from the hospital

  28 Days

Secondary Outcomes (12)

• Rate of viral elimination

  Days 3, 5, 7, 9, and 11

• Time to normalization of clinical symptoms

  28 Days

• Duration of oxygen therapy

  28 Days

• Change in the level of lung damage according to CT

  Days 15, 22, and 29

• Rate of transfer to the intensive care unit

  28 days

Study Arms (5)

Favipiravir, lower dose (pilot stage)

EXPERIMENTAL

1600mg BID on the 1st day followed by 600mg BID for 13 days

Drug: Favipiravir

Favipiravir, higher dose (pilot stage)

EXPERIMENTAL

1800mg BID on the 1st day followed by 800mg BID for 13 days

Drug: Favipiravir

Standard of care (pilot stage)

ACTIVE COMPARATOR

Based on approved clinical recommendations for treatment of COVID-19 in the Russian Federation (but not Favipiravir). Might include hydroxychloroquine, chloroquine, lopinavir/ritonavir or other recommended schemes.

Drug: Standard of Care

Favipiravir, selected dose (pivotal stage)

EXPERIMENTAL

The dose will be selected based on pilot study results.

Drug: Favipiravir

Standard of care (pivotal stage)

ACTIVE COMPARATOR

Based on approved clinical recommendations for treatment of COVID-19 in the Russian Federation (but not Favipiravir). Might include hydroxychloroquine, chloroquine, lopinavir/ritonavir or other recommended schemes.

Drug: Standard of Care

Interventions

Favipiravir DRUG

200 mg coated tablets

Also known as: Avifavir

Favipiravir, higher dose (pilot stage); Favipiravir, lower dose (pilot stage); Favipiravir, selected dose (pivotal stage)

Standard of Care DRUG

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.

Also known as: Hydroxychloroquine, chloroquine, lopinavir/ritonavir, etc.

Standard of care (pilot stage); Standard of care (pivotal stage)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Patient Information Sheet and Informed Consent form to participate in the study.
• Men and women aged 18 years and older.
• Patients hospitalized with a diagnosis of COVID-19.
• The diagnosis of COVID-19 was confirmed by positive reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2, performed no earlier than 7 days before hospitalization or at screening.
• Moderate severity of COVID-19 with pneumonia with at least 1 of the following symptoms:
• Fever above 38 °C;
• Cough;
• Shortness of breath during physical exertion;
• C reactive protein (CRP) of blood serum \> 10 mg/l;
• SpO2 \< 95%
• The capability of oral drug administration.
• The patients' consent to use adequate contraception methods during the study (condom with spermicide) and for 3 months following completion.

You may not qualify if:

• Severe type of disease, with at least one of the following criteria:
• Frequency of breath \> 35 per minute, which does not decrease after the body temperature drops to normal or subfebrile values;
• Blood oxygen saturation (SpO2) \< 90% at rest;
• Partial pressure of oxygen in arterial blood (PaO2) \< 60 mm Hg;
• Oxygenation index (RaO2/FiO2) ≤ 200 mm Hg;
• Partial pressure of CO2 in arterial blood (PaCO2) \< 60 mm Hg;
• Septic shock.
• Patients treated with lopinavir/ritonavir, ribavirin, arbidol, chloroquine, hydroxychloroquine, mefloquine, favipiravir within 7 days prior to screening.
• Severe cardiovascular diseases currently or 6 months prior to randomization, including: New York Heart Association (NYHA) Class III or IV chronic heart failure, clinically significant ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), unstable angina, myocardial infarction, heart and coronary vessel surgery, significant valvular heart disease, uncontrolled arterial hypertension with systolic blood pressure \> 180 mm Hg and diastolic blood pressure \> 110 mm Hg, pulmonary embolism or deep vein thrombosis.
• Severe chronic renal impairment (GFR \< 30 ml / min) or continuous renal replacement therapy, hemodialysis or peritoneal dialysis.
• A history of cirrhosis or an increase in alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) \> 5 times × upper limit of normal (ULN).
• Severe diseases of the central nervous system, including seizures in history or conditions that may lead to their development; stroke or transient ischemic attack within 12 months prior to screening; head injuries or loss of consciousness within 12 months prior to screening; a brain tumor.
• Significant uncontrolled concomitant disease, e.g. neurological, renal, hepatic, endocrinological or gastrointestinal disorder which according to the Investigator, could prevent the patient from participating in the study
• Malignancies that require chemotherapy within 6 months prior to screening.
• Known HIV infection

Sponsors & Collaborators

• Chromis LLC: lead
• Chemical Diversity Research Institute: collaborator

Study Sites (22)

Republican Clinical Hospital

Makhachkala, Russia

Location

"K+31" Clinic

Moscow, Russia

Location

"Khaven" Llc

Moscow, Russia

Location

Central Clinical Hospital with Polyclinic

Moscow, Russia

Location

Central Research Institute of Epidemiology

Moscow, Russia

Location

City Clinical Hospital n.a. O.M. Filatov

Moscow, Russia

Location

City Clinical Hospital named after S.S. Yudin

Moscow, Russia

Location

City Clinical Hospital No. 24

Moscow, Russia

Location

City Clinical Hospital No. 51

Moscow, Russia

Location

First Moscow State Medical University n.a. I.M. Sechenov

Moscow, Russia

Location

Moscow State University n.a. M. V. Lomonosov

Moscow, Russia

Location

National Medical and Surgical Center named after N.I. Pirogov

Moscow, Russia

Location

City Hospital № 33 of the Leninsky region of Nizhny Novgorod

Nizhny Novgorod, Russia

Location

Infectious clinical hospital No.2 of Nizhny Novgorod

Nizhny Novgorod, Russia

Location

Ryazan State Medical University named after I.P. Pavlov

Ryazan, Russia

Location

Military Medical Academy named after S.M. Kirova

Saint Petersburg, Russia

Location

Saratov State Medical University named after V.I. Razumovsky

Saratov, Russia

Location

Clinical hospital No.1

Smolensk, Russia

Location

Regional Clinic Hospital

Tver', Russia

Location

Bashkir State Medical University

Ufa, Russia

Location

Yakutsk City Clinical Hospital

Yakutsk, Russia

Location

Yaroslavl Regional Clinical Hospital for War Veterans

Yaroslavl, Russia

Location

Related Publications (1)

• Ivashchenko AA, Dmitriev KA, Vostokova NV, Azarova VN, Blinow AA, Egorova AN, Gordeev IG, Ilin AP, Karapetian RN, Kravchenko DV, Lomakin NV, Merkulova EA, Papazova NA, Pavlikova EP, Savchuk NP, Simakina EN, Sitdekov TA, Smolyarchuk EA, Tikhomolova EG, Yakubova EV, Ivachtchenko AV. AVIFAVIR for Treatment of Patients With Moderate Coronavirus Disease 2019 (COVID-19): Interim Results of a Phase II/III Multicenter Randomized Clinical Trial. Clin Infect Dis. 2021 Aug 2;73(3):531-534. doi: 10.1093/cid/ciaa1176.

  PMID: 32770240 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

favipiravir; Standard of Care; Hydroxychloroquine; Chloroquine; Lopinavir; Ritonavir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Study Officials

• Elena Pavlikova, MD,PhD,Prof

  Moscow State University n.a. M.V. Lomonosov

  PRINCIPAL INVESTIGATOR

• Nikita Lomakin, MD,PhD

  Central Clinical Hospital with Polyclinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an adaptive, multicenter, open-label, randomized clinical study of Favipiravir versus standard of care (SOC) in hospitalized patients with moderate to severe COVID-19 pneumonia.

Study Record Dates

• First Submitted: June 13, 2020
• First Posted: June 16, 2020
• Study Start: April 23, 2020
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: June 16, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

RU (22)