A phase 2, randomized, double-blind, placebo-controlled study of senolytic molecule UBX0101 in the treatment of painful knee osteoarthritis

Purpose: To assess the efficacy and safety of single-dose, intra-articular (IA) administration UBX0101 in patients with painful knee osteoarthritis (OA). is a p53/MDM2 interaction inhibitor that can induce apoptosis senescent synoviocytes. Results from recent Phase 1 study (NCT03513016) suggested IA had dose-dependent, clinically meaningful effects on pain function OA. Methods: This was 2, randomized, double-blind, placebo-controlled, parallel group OA randomized 1:1:1:1 to 0.5 mg, 2.0 4.0 mg or matched placebo. Key eligibility criteria included by ACR criteria, Kellgren-Lawrence grade (KLG) 1-4, mean daily between 4 9 Numeric Rating Scale (NRS, 0-10). Study duration 24 weeks. Clinical outcomes WOMAC (WOMAC-A) (WOMAC-C) sub-scores (each 0-4 Likert scale), NRS, patient global assessment (PGA) impression change (PGIC). The primary endpoint baseline (CFBL) WOMAC-A at Week 12. secondary endpoints CFBL 12 WOMAC-C weekly NRS scores. With 45 per group, 90% power an alpha 0.10 for two-sided comparison versus placebo effect size 0.50 assumed standard deviation 0.75 item score least square (LS) Results: A total 183 were randomized. population balanced regarding characteristics outcome measure values. Mean age 62.9 years, 64% female, 78% white. sub-score ranged 2.05 2.20. Decreases similar all treatment groups. LS means -0.924, -1.52, -1.019, -1.017 placebo, respectively. Secondary not met. An historically high response through confounded ability discern effect. Possible reasons this dosing route, and/or investigator expectedness, gender dimorphism reporting. Single doses up associated acceptable profile well-tolerated. Most adverse events (AEs) mild. Seven, non-related, serious AEs occurred during study; one death due coronary artery disease. Conclusions: 2 failed demonstrate single encouraging symptomatic improvements observed previous confirmed well-controlled, adequately powered study.