Tropomyosin-related kinase A (TrkA) inhibition for the treatment of painful knee osteoarthritis: results from a randomized controlled phase 2a trial

Osteoarthritis Cartilage. 2019 Nov;27(11):1590-1598. doi: 10.1016/j.joca.2019.05.029. Epub 2019 Jul 26.


Objective: To investigate the TrkA inhibitor, ASP7962, for treatment of painful knee osteoarthritis.

Design: Phase 2a, double-blind, placebo- and naproxen-controlled, double-dummy, parallel-group study. Adults with knee osteoarthritis were randomized (2:2:1) to ASP7962 (100 mg), placebo, or naproxen (500 mg) twice daily (BID) for 4 weeks. Primary endpoint: change from baseline to Week 4 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale score. Secondary endpoints: change from baseline to Weeks 1, 2, and End of Treatment (EoT) in WOMAC pain subscale score; change from baseline to Weeks 1, 2, 4, and EoT in WOMAC physical function and stiffness subscales, walking pain and WOMAC total scores; and change from baseline in daily average pain score.

Results: 215 participants were randomized (ASP7962 100 mg BID, n = 85; placebo, n = 87; naproxen 500 mg BID, n = 43). No significant difference was observed between ASP7962 and placebo in change from baseline to Week 4 in WOMAC pain subscale score (-0.14; 90% 2-sided CI: -0.62, 0.34; P = 0.316); a significant difference was observed between naproxen and placebo (-0.67; 80% 2-sided CI: -1.12, -0.23; P = 0.027). No differences were observed between ASP7962 and placebo in change from baseline in any WOMAC subscale score; statistically significant changes were observed between naproxen and placebo (P ≤ 0.01, all time points for all WOMAC endpoints). ASP7962 was safe and well-tolerated.

Conclusions: Four-week treatment with ASP7962 (100 mg BID) did not improve pain or physical function in individuals with painful knee osteoarthritis., NCT02611466; EudraCT Number, 2014-004996-22.

Keywords: ASP7962; Knee; Osteoarthritis; Pain; Physical function; TrkA inhibitor.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arthralgia / diagnosis
  • Arthralgia / drug therapy*
  • Arthralgia / etiology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Naproxen / therapeutic use*
  • Osteoarthritis, Knee / complications
  • Pain Measurement / methods
  • Receptor, trkA / antagonists & inhibitors*
  • Treatment Outcome
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • NTRK1 protein, human
  • Naproxen
  • Receptor, trkA

Associated data

  • EudraCT/2014-004996-22