Safety of the New Russian Anti-smallpox Medicinal Product NIOCH-14: Open, Randomised Phase I Clinical Trial Results

INTRODUCTION. Vaccination against smallpox was discontinued in 1980 following the success of the World Health Organization’s Smallpox Eradication Programme. Consequently, more than half of the current world population lacks immunity to orthopoxviruses pathogenic to humans. Since 2022, several countries have been reporting outbreaks of mpox (previously known as monkeypox), which necessitates developing new small molecules active against orthopoxviruses.AIM. The aim was to evaluate the safety and tolerability of NIOCH-14, a Russian anti-smallpox medicinal product, after oral administration in a phase I clinical trial.MATERIALS AND METHODS. The clinical trial was conducted in 90 healthy volunteers at the Federal State budgetary Institution of Healthcare ‘Medical and Sanitary Unit No. 163 of the Federal Medical and Biological Agency’ in accordance with Protocol No. NIOCH-01/20 ‘An open, simple, randomised study of the safety, tolerability, pharmacokinetics of NIOCH-14 in volunteers aged 18–50 years in parallel groups’. Investigators used a standard set of clinical, laboratory, and instrument-based testing methods. The clinical trial included six experimental groups of 15 subjects each. Groups 1, 2, and 3 received NIOCH-14 as a single oral dose of 200, 600, and 1200 mg, respectively. Groups 4, 5, and 6 received NIOCH-14 at daily oral doses of 200, 600, and 1200 mg/day, respectively, for 6 days.RESULTS. After single and repeated administration of NIOCH-14 at doses of 200, 600, and 1200 mg to volunteers, the study did not demonstrate any changes in the blood test results (erythrocyte, leucocyte, platelet, and differential leucocyte counts; haemoglobin levels; erythrocyte sedimentation rate values; alanine transaminase, aspartate transaminase, and alkaline phosphatase activity levels; total protein, total bilirubin, glucose, creatinine, urea, and C-reactive protein levels; prothrombin time ratios; thymol turbidity). Similarly, the urinalysis results remained unaltered throughout the entire observation period. No adverse events were observed in volunteers receiving NIOCH-14 at all single doses or repeated doses of 200 and 600 mg. One volunteer receiving the investigational medicinal product at a repeated dose of 1200 mg/day experienced transient epigastric pain on days 2 and 5.CONCLUSIONS. The physical examination, haematology, blood chemistry, and urinalysis results did not reveal any pathological changes in healthy volunteers. The investigational medicinal product, formulated as hard gelatin capsules containing 200 mg of NIOCH-14 and excipients, demonstrated a favourable safety and tolerability profile.REGISTRATION. This clinical trial is registered at ClinicalTrials.gov (NCT05976100).