LEVI-04 improves knee osteoarthritis outcomes

Treatment with LEVI-04—a p75 neurotrophin receptor (p75NTR) fusion protein that inhibits neurotrophin-3—helps improve pain and function in patients with knee osteoarthritis, as shown in a phase II trial.

The trial included 518 patients (mean age 64 years, 56.4 percent female) with painful (≥4/10 Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain scores) and radiographic knee osteoarthritis, enrolled at multiple sites across Denmark, Hong Kong, Poland, Moldova, and the Czech Republic.

The patients were randomly assigned to receive a monthly intravenous treatment with LEVI-04 at 0.3 mg/kg (n=130), 1 mg/kg (n=130), or 2 mg/kg (n=129) or placebo (n=129) for 16 weeks, with safety follow-up to week 30.

Change in WOMAC pain from randomization to week 17 was assessed in the intention-to treat population as the primary endpoint. Safety analyses included all participants who received the study drug.

At week 17, WOMAC pain decreased significantly with all doses of LEVI-04 vs placebo (0.3 mg/kg: mean difference, −0.51; p=0.023; 1 mg/kg: mean difference, −0.62; p=0.015; 2 mg/kg: mean difference, −0.79; p=0.0024). The effect sizes were 0.28, 0.33, and 0.43 for the respective LEVI-04 dose groups.

LEVI-04 did not appear to increase the incidence of serious adverse events, treatment-emergent adverse events (58 percent with 0.3 mg/kg, 66 percent with 1 mg/kg, 64 percent with 2 mg/kg, and 67 percent with placebo), and joint pathologies, including rapidly progressive osteoarthritis.