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

COVID-19 Clinical Trial

Official title:

An Adaptive, Multicenter, Randomized, Open-label, Comparative Clinical Study to Assess Efficacy and Safety of Favipiravir in Hospitalized Patients With COVID-19

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04434248
• Other study ID #: COVID-FPR-01
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: April 23, 2020
• Est. completion date: July 2020

Study information

• Verified date: June 2020
• Source: Chromis LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

At the pilot stage: upon signing the informed consent form and screening, 60 eligible patients with polymerase chain reaction (PCR) confirmed COVID-19 pneumonia are randomized at a 1:1:1 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 Favipiravir 1800 mg BID on Day 1 followed by 800 mg BID on Days 2-14 (1800/800 mg), or SOC.

At the pivotal stage: additional 270 eligible patients are randomized at a 1:1 ratio to receive either Favipiravir (the dose regimen depends of the subject's weight) or SOC.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 330
• Est. completion date: July 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed Patient Information Sheet and Informed Consent form to participate in the study.

2. Men and women aged 18 years and older.

3. Patients hospitalized with a diagnosis of COVID-19.

4. 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.

5. 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%

6. The capability of oral drug administration.

7. The patients' consent to use adequate contraception methods during the study (condom with spermicide) and for 3 months following completion.

Exclusion Criteria:

1. 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.

2. Patients treated with lopinavir/ritonavir, ribavirin, arbidol, chloroquine, hydroxychloroquine, mefloquine, favipiravir within 7 days prior to screening.

3. 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.

4. Severe chronic renal impairment (GFR < 30 ml / min) or continuous renal replacement therapy, hemodialysis or peritoneal dialysis.

5. A history of cirrhosis or an increase in alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) > 5 times × upper limit of normal (ULN).

6. 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.

7. 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

8. Malignancies that require chemotherapy within 6 months prior to screening.

9. Known HIV infection

10. Hypersensitivity to any component of the study drug.

11. Participation in other clinical studies or taking other study drugs within 28 days prior to screening.

12. Pregnant or lactating women or women planning to get pregnant during the clinical study; women of child-bearing potential (including non-sterilized by surgical means and during the post-menopause period less than 2 years) who do not use adequate contraception methods.

13. Inability to read or write, unwillingness to understand and follow procedures of study protocol, as well as any other concomitant medical or serious mental conditions that make the patient unfit to participate in the study, limit the legality of obtaining informed consent or can affect patient's ability to participate in the study.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Favipiravir
200 mg coated tablets
• 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.

Locations

Country	Name	City	State
Russian Federation	Republican Clinical Hospital	Makhachkala
Russian Federation	"K+31" Clinic	Moscow
Russian Federation	"Khaven" Llc	Moscow
Russian Federation	Central Clinical Hospital with Polyclinic	Moscow
Russian Federation	Central Research Institute of Epidemiology	Moscow
Russian Federation	City Clinical Hospital n.a. O.M. Filatov	Moscow
Russian Federation	City Clinical Hospital named after S.S. Yudin	Moscow
Russian Federation	City Clinical Hospital No. 24	Moscow
Russian Federation	City Clinical Hospital No. 51	Moscow
Russian Federation	First Moscow State Medical University n.a. I.M. Sechenov	Moscow
Russian Federation	Moscow State University n.a. M. V. Lomonosov	Moscow
Russian Federation	National Medical and Surgical Center named after N.I. Pirogov	Moscow
Russian Federation	City Hospital ? 33 of the Leninsky region of Nizhny Novgorod	Nizhny Novgorod
Russian Federation	Infectious clinical hospital No.2 of Nizhny Novgorod	Nizhny Novgorod
Russian Federation	Ryazan State Medical University named after I.P. Pavlov	Ryazan
Russian Federation	Military Medical Academy named after S.M. Kirova	Saint Petersburg
Russian Federation	Saratov State Medical University named after V.I. Razumovsky	Saratov
Russian Federation	Clinical hospital No.1	Smolensk
Russian Federation	Regional Clinic Hospital	Tver
Russian Federation	Bashkir State Medical University	Ufa
Russian Federation	Yakutsk City Clinical Hospital	Yakutsk
Russian Federation	Yaroslavl Regional Clinical Hospital for War Veterans	Yaroslavl

Sponsors (2)

Lead Sponsor	Collaborator
Chromis LLC	Chemical Diversity Research Institute

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Time to viral elimination [pivotal stage]	Median time to reach undetectable SARS-CoV-2 RNA level	28 Days
Primary	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	Rate of viral elimination	Percent of patients with undetectable SARS-CoV-2 RNA level	Days 3, 5, 7, 9, and 11
Secondary	Time to normalization of clinical symptoms	Median time [days] to reach normal levels of clinical indicators (body temperature, SpO2, breathing rate)	28 Days
Secondary	Duration of oxygen therapy	Mean duration of oxygen therapy [days]	28 Days
Secondary	Change in the level of lung damage according to CT	Change of lung damage level according to CT comparing to baseline [% of patients]	Days 15, 22, and 29
Secondary	Rate of transfer to the intensive care unit	Percent of patients transferred to the intensive care unit [% of patients]	28 days
Secondary	Rate of the use of non-invasive lung ventilation	Percent of patients undergoing non-invasive lung ventilation [% of patients]	28 days
Secondary	Rate of the use of mechanical ventilation	Percent of patients undergoing mechanical ventilation [% of patients]	28 days
Secondary	Mortality	Percent of patients died within 28-days period [% of patients]	28 days
Secondary	Peak plasma concentration (Cmax)	Determination of Cmax [ng/ml]	Day 1
Secondary	Time to peak plasma concentration (Tmax)	Determination of Tmax [h]	Day 1
Secondary	Area under the plasma concentration versus time curve (AUC0-t)	Determination of AUC0-t [ng*h/ml]	10 days
Secondary	Trough plasma concentration (Ctrough)	Determination of Ctrough [ng/ml]	10 days