Trial Outcomes & Findings for Oral Favipiravir Compared to Placebo in Subjects With Mild COVID-19 (NCT NCT04346628)

NCT ID: NCT04346628

Last Updated: 2022-07-13

Results Overview

Time in days from randomization to the first two negative results of nasal and/or oropharyngeal swab.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

149 participants

Primary outcome timeframe

Up to 28 days

Results posted on

2022-07-13

Participant Flow

385 participants were assessed for eligibility; 149 participants were enrolled and randomized.

Participant milestones

Participant milestones
Measure	Placebo In addition to standard of care (SOC) treatment for COVID-19 infection, participants were randomized to receive placebo to match favipiravir for 10 days, and to be evaluated for health outcomes through day 28.	Favipiravir In addition to SOC treatment for COVID-19 infection, participants were randomized to receive favipiravir for 10 days, and to be evaluated for health outcomes through day 28. Favipiravir was administered orally, 1800 mg on the first dose (day 1) followed by 800 mg twice daily for the next 9 days (days 2-10).
Overall Study STARTED	74	75
Overall Study Intention-to-treat (ITT) Analysis Set	74	75
Overall Study Symptomatic Modified ITT (smITT) Analysis Set	70	65
Overall Study Modified ITT (mITT) Analysis	57	59
Overall Study COMPLETED	68	62
Overall Study NOT COMPLETED	6	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo In addition to standard of care (SOC) treatment for COVID-19 infection, participants were randomized to receive placebo to match favipiravir for 10 days, and to be evaluated for health outcomes through day 28.	Favipiravir In addition to SOC treatment for COVID-19 infection, participants were randomized to receive favipiravir for 10 days, and to be evaluated for health outcomes through day 28. Favipiravir was administered orally, 1800 mg on the first dose (day 1) followed by 800 mg twice daily for the next 9 days (days 2-10).
Overall Study Lost to Follow-up	4	4
Overall Study Withdrew (had personal reasons)	2	5
Overall Study Withdrew (medication intolerant)	0	3
Overall Study Withdrew (declined intervention)	0	1

Baseline Characteristics

Participants in the smITT Analysis Set and the mITT Analysis Set.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Up to 28 days

Population: Modified intention-to-treat (mITT) Analysis Set (participants who were symptomatic with positive RT-PCR result at baseline)

Time in days from randomization to the first two negative results of nasal and/or oropharyngeal swab.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants In addition to standard of care (SOC) treatment for COVID-19 infection, participants were randomized to receive placebo to match favipiravir for 10 days, and to be evaluated for health outcomes through day 28.	Favipiravir n=59 Participants In addition to SOC treatment for COVID-19 infection, participants were randomized to receive favipiravir for 10 days, and to be evaluated for health outcomes through day 28. Favipiravir was administered orally, 1800 mg on the first dose (day 1) followed by 800 mg twice daily for the next 9 days (days 2-10).
Time Until Cessation of Oral Shedding of SARS-CoV-2 Virus	13 days Interval 9.0 to 14.0	14 days Interval 9.0 to 21.0

SECONDARY outcome

Timeframe: Up to 28 days

Population: mITT Analysis Set (participants who were symptomatic with positive RT-PCR result at baseline)

Viral load (nucleic acid) will be assessed by RT-PCR Ct over time. Cycle threshold (Ct) denotes how many PCR cycles are required before the SARS-CoV-2 viral RNA reached a detectable level. Higher Ct values correspond to lower viral copy numbers. For reference, Ct values of 20 correspond to \~2.12 x 106 viral copies per milliliter, while a Ct value of 40 is undetectable and is considered the lower limit of detection of this RT-PCR test for SARS-CoV-2.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants In addition to standard of care (SOC) treatment for COVID-19 infection, participants were randomized to receive placebo to match favipiravir for 10 days, and to be evaluated for health outcomes through day 28.	Favipiravir n=59 Participants In addition to SOC treatment for COVID-19 infection, participants were randomized to receive favipiravir for 10 days, and to be evaluated for health outcomes through day 28. Favipiravir was administered orally, 1800 mg on the first dose (day 1) followed by 800 mg twice daily for the next 9 days (days 2-10).
Sars-CoV-2 Viral Load Day 1	25.1 cycles Interval 22.2 to 28.9	22.2 cycles Interval 19.7 to 27.2
Sars-CoV-2 Viral Load Day 5	27.3 cycles Interval 25.2 to 33.5	27.9 cycles Interval 24.7 to 31.9
Sars-CoV-2 Viral Load Day 10	37.3 cycles Interval 33.1 to 40.0	40.0 cycles Interval 33.1 to 40.0
Sars-CoV-2 Viral Load Day 28	40.0 cycles Interval 40.0 to 40.0	40.0 cycles Interval 40.0 to 40.0

SECONDARY outcome

Timeframe: Up to 28 days

Population: Intention-to-treat (ITT) analysis set

Clinical worsening is reported as the number of participants with hospitalization or emergency department (ED) visits.

Outcome measures

Outcome measures
Measure	Placebo n=74 Participants In addition to standard of care (SOC) treatment for COVID-19 infection, participants were randomized to receive placebo to match favipiravir for 10 days, and to be evaluated for health outcomes through day 28.	Favipiravir n=75 Participants In addition to SOC treatment for COVID-19 infection, participants were randomized to receive favipiravir for 10 days, and to be evaluated for health outcomes through day 28. Favipiravir was administered orally, 1800 mg on the first dose (day 1) followed by 800 mg twice daily for the next 9 days (days 2-10).
Count of Participants With Clinical Worsening of COVID-19 Disease Hospitalization	4 Participants	0 Participants
Count of Participants With Clinical Worsening of COVID-19 Disease ED visit	7 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 28 days

Population: ITT analysis set; participants with available data at each time point are included in the analysis

Outcome measures

Outcome measures
Measure	Placebo n=74 Participants In addition to standard of care (SOC) treatment for COVID-19 infection, participants were randomized to receive placebo to match favipiravir for 10 days, and to be evaluated for health outcomes through day 28.	Favipiravir n=75 Participants In addition to SOC treatment for COVID-19 infection, participants were randomized to receive favipiravir for 10 days, and to be evaluated for health outcomes through day 28. Favipiravir was administered orally, 1800 mg on the first dose (day 1) followed by 800 mg twice daily for the next 9 days (days 2-10).
Count of Participants With Development of SARS-CoV-2 Antibodies Baseline	12 Participants	9 Participants
Count of Participants With Development of SARS-CoV-2 Antibodies Day 28	47 Participants	40 Participants

SECONDARY outcome

Timeframe: Up to 28 days

Population: Symptomatic Modified Intention-to-treat (smITT) Analysis Set (participants reported at least one symptom other than mild cough, mild fatigue, or decreased taste/smell at baseline)

Time until cessation of symptoms is reported as days until initial resolution and sustained resolution of symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=70 Participants In addition to standard of care (SOC) treatment for COVID-19 infection, participants were randomized to receive placebo to match favipiravir for 10 days, and to be evaluated for health outcomes through day 28.	Favipiravir n=65 Participants In addition to SOC treatment for COVID-19 infection, participants were randomized to receive favipiravir for 10 days, and to be evaluated for health outcomes through day 28. Favipiravir was administered orally, 1800 mg on the first dose (day 1) followed by 800 mg twice daily for the next 9 days (days 2-10).
Time Until Cessation of Symptoms Initial resolution of symptoms	14 days Interval 11.0 to 18.0	15 days Interval 12.0 to 26.0
Time Until Cessation of Symptoms Sustained resolution of symptoms	24 days Interval 21.0 to Not estimable (curve did not reach the 75th percentile)	NA days Interval 26.0 to Not estimable (curve did not reach either the median or the 75th percentile)

SECONDARY outcome

Timeframe: Up to 28 days

Population: smITT Analysis Set (participants reported at least one symptom other than mild cough, mild fatigue, or decreased taste/smell at baseline)

This outcome will be assessed in patient who are asymptomatic of COVID-19 infection at the time of enrollment

Outcome measures

Outcome measures
Measure	Placebo n=70 Participants In addition to standard of care (SOC) treatment for COVID-19 infection, participants were randomized to receive placebo to match favipiravir for 10 days, and to be evaluated for health outcomes through day 28.	Favipiravir n=65 Participants In addition to SOC treatment for COVID-19 infection, participants were randomized to receive favipiravir for 10 days, and to be evaluated for health outcomes through day 28. Favipiravir was administered orally, 1800 mg on the first dose (day 1) followed by 800 mg twice daily for the next 9 days (days 2-10).
Count of Participant With Absence of Development of Any Symptoms	2 Participants	5 Participants

SECONDARY outcome

Timeframe: Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration)

Population: Data were not collected for this outcome measure.

Cmax is a pharmacokinetic parameter that measures the maximum concentration of drug in plasma.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration)

Population: Data were not collected for this outcome measure.

Cmin is a pharmacokinetic parameter that measures the minimum concentration of drug in plasma.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Favipiravir

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=74 participants at risk In addition to standard of care (SOC) treatment for COVID-19 infection, participants were randomized to receive placebo to match favipiravir for 10 days, and to be evaluated for health outcomes through day 28.	Favipiravir n=75 participants at risk In addition to SOC treatment for COVID-19 infection, participants were randomized to receive favipiravir for 10 days, and to be evaluated for health outcomes through day 28. Favipiravir was administered orally, 1800 mg on the first dose (day 1) followed by 800 mg twice daily for the next 9 days (days 2-10).
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress Syndrome (ARDS)	1.4% 1/74 • 28 days	0.00% 0/75 • 28 days

Other adverse events

Adverse event data not reported

Additional Information

Yvonne A. Maldonado, MD

Stanford University

Phone: (650) 723-5682

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place