A Kuwait-based clinical trial sponsored by Indian generic drug producer Dr. Reddy’s Laboratory was recently terminated as the resulting data failed to evidence a statistically significant difference for the primary endpoint. That is the time to sustain hypoxia resolution for the study drug known as Avigan versus the placebo wasn’t statistically significant. Totaling 353 study subjects, the complete analysis for this segment of the study is forecast for the end of February. An analysis of a low-risk subgroup in this study points to potential support of the hypothesis that use of Favipiravir in early onset COVID-19 can lead to reduced hospitalization duration. In the meantime, however, the sponsor will continue their ten Phase 3 clinical trials targeting outpatient (ambulatory) settings. That is, those studies targeting patients with mild to moderate COVID-19 symptoms in North America in conjunction with Appili Therapeutics and Global Response Aid. In fact, TrialSite reported that this trio quietly submitted the drug, again known as Favipiravir its trade name Avigan, for commercial authorization with Health Canada just in December.
This prospective, interventional, multi-center Phase 3 clinical trial (NCT04529499) sought to evaluate the efficacy, safety and tolerability of favipiravir as adjunct to supportive care in comparison to placebo with supportive care, in the acute treatment of patients who have tested positive for COVID-19 and present moderate to severe symptoms. Conducted in two parts, including 1) main study, and 2) extended follow up, the formal study title is “A Multi-Center, Randomized, Double Blind, Placebo Controlled Clinical Trial Evaluating the Efficacy and Safety of Favipiravir in Moderate to Severe COVID-19 Patients.”
In the experimental drug arm included patients took favipiravir (Avigan) tablets (200 mg) twice daily—once in the morning and once in the evening. The dosage was 1,800 mg twice daily on Day 1 + 800 mg BID for the next 9 days. On Day 1 the second dose was administered with at least a 4-hour interval from administration of the first dose.
The study’s primary endpoint was targeted as a patient who has attained a score of 4 or lower on the 10-point ordinal scale of clinical status used by the World Health Organization (WHO) in the SOLIDARITY trial which in this case equaled the maintaining of blood oxygen saturation of ≥ 95% at rest on room air at sea level when evaluated over a 24 hour period. A number of secondary measures were established as well. The study was led by Sagar Munjal, MD, MS, Vice President & Head of Clinical Development, Operations and Medical Affairs.
The Preliminary Results
The company reported that the Kuwait CVD-04-CD-001 study failed to show a statistically significant difference for the primary endpoint (i.e. time to sustained hypoxia resolution) for Avigan versus placebo (7 days vs. 8 days; p=>0.05). The company reports the full analysis will be available on the 353 subjects by end of Feb. 2021.
Dr. Reddy’s reported that the sponsor performed a subgroup analysis on 181 patients in the low risk category. The preliminary results here demonstrate a 3 day earlier discharge in the Avigan group as compared to the placebo group (8 days vs. 11 days; p=0.0063) for time to hospital discharge secondary endpoint.
The sponsor suggests in their recent press release that the results for this low risk category may support the hypothesis that favipiravir may be effective as part of an early onset COVID-19 treatment regimen but not to be used for late-stage hospital treatment for moderate and severe COVID-19 patients.
The Research Sites
This research was conducted at Jaber Al-Ahmad Al-Sabah Hospital in South Surra, Kuwait City, as well as at Mishref Field Hospital also in Kuwait City.
Salman Khalifa Al-Sabah, MD, Principal Investigator, Jaber Al-Ahmad Al-Sabah Hospital
Mohammad S.M.D. Al Humaidan, MBBS, Principal Investigator, Mishref Field Hospital