Intra-articular MM-II for the treatment of knee osteoarthritis pain: Efficacy and safety results from a 26-week, phase 2b, placebo-controlled, double-blind, randomized dose-ranging trial

Abstract

Objective: Determine optimal dose, efficacy, and safety of MM-II, a suspension of large empty liposomes, for knee osteoarthritis (OA) pain.

Method: A double-blind phase 2b study (NCT04506463) randomized participants 3:3:3:1:3:1 to one intra-articular injection of 1, 3, or 6 mL MM-II or 1, 3, or 6 mL placebo, respectively. Inclusion criteria included age ≥40 years and radiographic and symptomatic knee OA. The primary endpoint was change from baseline in Western Ontario and McMaster Universities OA Index (WOMAC) pain (range, 0-4) 12 weeks post-injection (multiplicity-adjusted). Secondary endpoints included weekly average of daily knee pain (WADP), WOMAC pain at other visits, WOMAC function, patient global assessment (PtGA), and rescue medication use. Safety was assessed by treatment-emergent adverse events (TEAEs).

Results: Overall, 396 participants received treatment. In the 3 mL MM-II vs placebo group, WOMAC pain numerically improved at week 12 (least squares mean difference [95% confidence interval], -0.24 [-0.48, 0.00]; unadjusted P = 0.047; multiplicity-adjusted P = 0.085 [primary endpoint not met]). In the same 3 mL group, WADP showed improvements at week 12 (-10.9 [-18.9, -2.8]) lasting through week 26 (-11.8 [-20.4, -3.3]; unadjusted P <0.01 at both time points). Numeric improvements were also seen in WOMAC function from week 8-26, and PtGA at weeks 16 and 26. Rescue medication use with 3 mL MM-II was consistent with reduced pain. Results were numerically superior with 3 mL MM-II vs 1 mL MM-II; 6 mL MM-II was the least efficacious dose. MM-II was well tolerated, with low TEAE incidence.

Conclusion: MM-II was safe, and the optimal effective dose for the treatment of knee OA pain was 3 mL.

Keywords: Clinical trial; Knee; Liposome; MM-II; Osteoarthritis; Pain; Phase 2.