Objectively Measuring Pain and Function in Osteoarthritis, With Philip Conaghan, MBBS, PhD

LEVI-04 meaningfully improved pain and function in people with knee osteoarthritis (OA) in new analyses from a phase 2 trial.

New data on LEVI-04, a first-in-class p75 neurotrophin receptor-Fc fusion protein, were presented by Philip Conaghan, MBBS, PhD, Director, NIHR Leeds Biomedical Research Centre, and Professor of Musculoskeletal Medicine at University of Leeds at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois.

LEVI-04 was evaluated in a multicenter, randomized, placebo-controlled phase 2 trial that enrolled 518 adults with radiographically confirmed (Kellgren-Lawrence grade ≥2) and symptomatic knee OA (≥4/10 WOMAC and ≥4/10 average weekly pain). Participants received intravenous placebo or LEVI-04 at doses of 0.3, 1.0, or 2.0 mg/kg at baseline and every 4 weeks through week 16. The study primarily assessed change in WOMAC pain at week 17, with additional assessments of WOMAC function, stiffness, patient global assessment (PGA), and average weekly numerical rating scale (NRS) pain.

Conaghan and colleagues found that LEVI-04 achieved statistically significant improvements in WOMAC pain versus placebo across all doses in a dose-dependent fashion. The investigators also assessed pain on movement with the Staircase-Evoked Pain Procedure (StEPP) and found that a greater proportion of participants treated with LEVI-04 achieved the minimum clinically important difference (MCID) of 2 points in the StEPP versus placebo, with statistical significance observed in the 1.0 and 2.0 mg/kg groups.

HCPLive spoke with Conaghan to learn more about the study and the novel StEPP test that shows potential to be used as an objective measure on pain and function for people with knee OA.

"What we see that more people on LEVI-04 for all 3 doses achieved a clinically relevant reduction in that step function. So in other words, they were able to do more steps. Their pain related to steps was reduced, and that's really important for osteoarthritis, which is a disease where all the pain is related to how much you walk," Conaghan said.

Conaghan's disclosures include AbbVie/Abbott, Alfasigma, Eli Lilly, Eupraxia, Formation Bio, Galapagos, Genascence, Grunenthal, Janssen, Kolon TissueGene, Levicept, Medipost, Moebius Medical, Novartis, Orion, Pacira, Sandoz, Stryker, and Takeda.

Reference

Conaghan P, Katz N, Bihlet A, et al. LEVI-04, a Novel Neurotrophin-3 Inhibitor, Demonstrates Clinically Meaningful Improvements in Pain and Physical Function across a Range of OA Outcomes, Including the Staircase-Evoked Pain Procedure (StEPP). Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #2101