PHASE III TRIAL of MOLNUPIRAVIR in ADULTS with MILD SARS-CoV-2 INFECTION in INDIA

ABSTRACT

Background: To improve the management of SARS-Co2 infection there is an urgent unmet need for an orally administered antiviral drug to prevent disease progression, hospitalization, and clinical complications. Molnupiravir was developed in response to this need. This study assesses its efficacy and safety in Indian patients with mild SARS-CoV2 infection. Methods: This study is a phase III multi-centre open label randomized controlled trial of oral molnupiravir plus standard of care (MOL/SOC) versus SOC alone in Indian adults with mild SARS-CoV2 infection. The molnupiravir formulation used was developed and manufactured by HETERO LABS LTD, Hyderabad, India, under license from MERCK INC, NJ, USA. Eligible patients with RT PCR-confirmed mild SARS CoV2 infection, uncomplicated upper respiratory tract infection, with mild symptoms without any evidence of breathlessness, were randomized 11 to either oral MOL 800 mg b.i.d. for 5 days plus SOC or SOC alone. The primary endpoint was rate of hospitalization up to day 14. Secondary endpoints included proportion with a 2-point improvement in WHO 11-Point Clinical Progression Scale and rate of SARS CoV2 RT PCR negativity in naso/oropharyngeal swab at day 5, 10 and 14 and incidence of adverse events. Results: Of 1284 patients screened, 1218 were eligible and randomized, 608 to MOL+SOC, and 610 to SOC. The population consisted mainly of male patients (68%). Both arms were well balanced for age, height and weight. In the MOL/SOC arm 9 patients (1.5%) required hospitalisation vs. 26 (4.3%) in the SOC arm (p<0.01). In the MOL/SOC arm 80.8%, 95.6% and 97.4% had clinical improvement by Day 5, 10 and 14, respectively, compared to 32.1%, 74.3% and 94.1% in the SOC arm (p<0.0001 at day 5 and 10, and <0.01 at day 14). The rate of SARS CoV2 negativity was 77.1%, 91.3% and 93.9% in MOL/SOC vs. 29.3%, 70.2% and 89.0% in SOC at day 5, 10 and 14, respectively (p<0.001). There were no serious adverse events. Mild and self-limiting adverse events occurred in 4.8% of MOL/SOC and 2.6% of SOC participants. The most common adverse events were neurological (headache, somnolence) and gastrointestinal. Conclusion: A lower rate of hospitalisation, earlier clinical improvement, and earlier SARS CoV2 RT PCR negativity document superiority of Molnupiravir to SOC in mild SARS-CoV2 infection in this trial in India. Molnupiravir was well tolerated adverse events were mild and rare.