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

F. E. Watt, M. B. Blauwet, A. Fakhoury, H. Jacobs, R. Smulders, N. E. Lane

Research output: Contribution to journalArticle

Abstract

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. ClinicalTrials.gov, NCT02611466; EudraCT Number, 2014-004996-22.

Original languageEnglish (US)
Pages (from-to)1590-1598
Number of pages9
JournalOsteoarthritis and Cartilage
Volume27
Issue number11
DOIs
StatePublished - Nov 2019

Fingerprint

Knee Osteoarthritis
Naproxen
Placebos
Pain
Stiffness
Therapeutics
Ontario
tropomyosin kinase
Inhibition (Psychology)
Walking
Arthritis

Keywords

  • ASP7962
  • Knee
  • Osteoarthritis
  • Pain
  • Physical function
  • TrkA inhibitor

ASJC Scopus subject areas

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine

Cite this

Tropomyosin-related kinase A (TrkA) inhibition for the treatment of painful knee osteoarthritis : results from a randomized controlled phase 2a trial. / Watt, F. E.; Blauwet, M. B.; Fakhoury, A.; Jacobs, H.; Smulders, R.; Lane, N. E.

In: Osteoarthritis and Cartilage, Vol. 27, No. 11, 11.2019, p. 1590-1598.

Research output: Contribution to journalArticle

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abstract = "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. ClinicalTrials.gov, NCT02611466; EudraCT Number, 2014-004996-22.",
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AU - Jacobs, H.

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AU - Lane, N. E.

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N2 - 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. ClinicalTrials.gov, NCT02611466; EudraCT Number, 2014-004996-22.

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