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Phase III clinical trial of favipiravir in early-onset COVID-19 patients with severe risk factors
-Placebo-controlled, stratified Randomized, Multicenter, Double-blind study -

Phase III clinical trial of favipiravir in early-onset COVID-19 patients with severe risk factors

84

The study enrolled 84 unvaccinated COVID-19 patients who aged 20 years or older and had onset symptoms within 72 hours (early-onset). The patients had comorbidities with one or more risk factors for severe disease progression such as malignancy, COPD, cardiovascular disease, chronic lung disease, cerebrovascular disease, chronic kidney disease, type 2 diabetes, hypertension, dyslipidaemia, obesity (BMI >=30 kg/m2), smoking habits or aged 65 years or older. The gender of patients enrolled was 60-70% male in both the favipiravir and placebo groups. Age and BMI were similar in the favipiravir and placebo groups. The mean time from onset to initiation of treatment was similar in the favipiravir and placebo groups, 45.5 and 47.5 hours respectively.

The purpose of this study was to verify that the effectiveness in suppressing disease progression of Favipiravir (1800 mg twice daily on day 1, followed by 800 mg twice daily from days 2 to 10: 1800/800 mg BID) outweighed that of placebo. Forty-one patients in the favipiravir group and 43 patients in the placebo group included in the ITT population. The efficacy analyses were conducted in these patients. The primary efficacy endpoint was the proportion of patients who experienced disease progression from randomization to day 28. The disease progression defined as a score of 4 or higher (e.g. requiring oxygen therapy or death) based on a 7-point ordinal scale.

No deaths were reported in this study. Serious adverse events (SAEs) occurred in one patient in the favipiravir group (appendicitis) and one patient in the placebo group (aspiration pneumonia). There was no SAE related to the study drug. One AE (liver function abnormality) occurred in one patient in the favipiravir group, which was a reason for discontinuation of treatment. The incidence of AEs was 56.1% (23/41) in the favipiravir group and 60.5% (26/43) in the placebo group; the incidence of AEs related to the study drug was 14.6% (6/41) in the favipiravir group and 14.0% (6/43) in the placebo group, similar in both groups. With regard to AEs related to the study drug, the relatively high number of AEs (>=3%) in the favipiravir group were all mild, no new AEs should be added to the safety profile.

The study was discontinued before the target number of 316 patients was reached, as the rapid uptake of SARS-CoV-2 vaccines and the emergence of SARS-CoV-2 Omicron mutant variant, that made it difficult to enroll the number of patients planned at the beginning of this study. Therefore, the conclusion of efficacy were based on an analysis of the finally enrolled 84 patients. With regard to the primary endpoint, the proportion of patients with disease progression from randomization to Day 28 were 29.3% in the favipiravir group and 27.9% in the placebo group.

In this study, 84 COVID-19 patients with onset within 72 hours and at risk of severe disease progression were treated with favipiravir (1800/800 mg BID) or placebo for 10 days. No favipiravir was effective in suppressing severe disease in these patients, but the efficacy of favipiravir in patients within 48 hours of onset was suggested. Regarding safety, no deaths or SAEs causally related to favipiravir were reported, and no major problems in clinical use were observed.

Oct. 21, 2023

https://doi.org/10.1016/j.jiac.2023.10.010

No

https://jrct.niph.go.jp/latest-detail/jRCT2041210004

Sakurai Tsutomu

FUJIFILM Toyama Chemical Co., Ltd.

2-14-1,Kyoubashi,Chuo-ku,Tokyo,Japan

fftc-clinicaltrial-info1@fujifilm.com

Officer Clinical Trial Information

FUJIFILM Toyama Chemical Co., Ltd

2-14-1,Kyoubashi,Chuo-ku,Tokyo,Japan

+81-3-6228-3129

fftc-clinicaltrial-info1@fujifilm.com

Complete

April. 14, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

prevention purpose

1. Patients with positive SARS-CoV-2 test result by RT-PCR or loop-mediated isothermal amplification (LAMP) method or antigen test.
2. Patient within 72 hours from onset of first COVID-19 symptom
3. Patients with risk factors of progression to severe disease
4. Have a negative pregnancy test before study treatment
5. Patients can obtain written informed consent from the patients.
6. Other

1. Patients receiving oxygen therapy prior to the start of study treatment.
2. Patients with any of COVID-19 clinical symptoms/findings of dyspnea or a respiratory rate of 30 breaths/min or more.
3. Patients with SARS-CoV-2 vaccinated

Both

COVID-19 patients with risk factors of progression to severe disease onset within 72 hours prior to

Favipiravir group:
T-705a tablets 200 mg are administrated orally, 9 tablets twice daily for Day 1 and 4 tablets twice daily for Day 2 to 10.
Placebo group:
Placebo tablets are administered orally, 9 tablets twice daily for Day 1 and 4 tablets twice daily for Day 2 to 10.

Percentage of patients with severe disease from randomization to Day 28

1.Efficacy Endpoints
Incidence of progression to severe disease by Day 15
Change in the viral load of SARS-CoV-2
Time to negative for SARS-CoV-2
Change in the percentage of SARS-CoV-2 becoming negative
Time to progression to severe disease
symptoms and findings
Duration of oxygenation
2.Pharmacokinetics and PK-PD Endpoints
Plasma concentrations of favipiravir over time
PK prameters (AUC0-24, Cmax, Cmin) for favipiravir
3.Safety Endpoints
Adverse events
Laboratory tests
Vital signs

+81-76-434-7151

Mar. 25, 2021

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