Levicept Ltd presented positive results from its Phase II trial of LEVI-04, a novel neurotrophin-3 (NT-3) inhibitor, for the treatment of moderate to severe osteoarthritis at the American College of Rheumatology (ACR) Convergence 2024. The study, involving 518 participants with osteoarthritis of the knee, demonstrated significant pain reduction and improvements in function and stiffness.
The multi-arm, multicenter, randomized, double-blind, placebo-controlled Phase II study (NCT05618782) evaluated the efficacy and safety of LEVI-04. LEVI-04, a proprietary p75 neurotrophin receptor fusion protein (p75NTR-Fc), works by inhibiting NT-3 activity, modulating excess neurotrophin levels present in osteoarthritis.
Efficacy Results
The trial met its primary endpoint, with all doses of LEVI-04 (0.3mg/kg, 1mg/kg, 2mg/kg) showing statistically significant differences compared to placebo in the WOMACi pain assessment (change from baseline at Week 17) (p<0.05). The mean reduction in WOMAC pain score from baseline was greater than 50% for all three doses. More than 50% of LEVI-04-treated patients reported ≥50% reduction in pain, and >35% reported ≥70% reduction at week 17.
Secondary endpoints, including WOMAC subscales for function and joint stiffness, patient global assessment, and daily pain scores, also showed statistically significant improvements compared to placebo.
Safety Profile
LEVI-04 was well-tolerated, with safety monitoring and peripheral nervous system assessments revealing no increased incidence of serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), or joint pathologies, including rapidly progressive osteoarthritis, compared to placebo. This was confirmed via detailed radiographic analysis.
Expert Commentary
Professor Philip Conaghan MBBS PhD, Director NIHR Leeds Biomedical Research Centre and Principal Investigator, stated, "We believe these are truly exceptional results from a robust and well-designed study. LEVI-04 demonstrated significant and clinically meaningful improvement in pain, function and other outcomes and was well tolerated at all doses studied."
Eliot Forster, CEO of Levicept, added, "The selection of Levicept’s Phase II results as an oral presentation at ACR Convergence highlights their importance and reinforces our confidence that LEVI-04 could represent a genuine breakthrough in the treatment of osteoarthritis. We are now focused on strategic options to advance LEVI-04’s development and ensuring the best opportunity for it to reach the many patients who may benefit."
