• E Krupka, G-L Jiang, and C Jan.
• Sanofi R&D, 371, Rue du Professeur Joseph Blayac, 34184 Montpellier, France. Electronic address: emmanuel.krupka@sanofi.com.
• Osteoarthr. Cartil. 2019 Nov 1; 27 (11): 1599-1607.

ObjectiveThis trial evaluated the efficacy and safety of GZ389988A, a tropomyosin receptor kinase A (TrkA) inhibitor, in subjects with painful knee osteoarthritis (OA).MethodIn this single center, double-blind, placebo-controlled and randomized trial, 104 subjects with moderate-to-severe knee OA pain were enrolled to receive a single intra-articular (IA) injection of either GZ389988A or placebo. Efficacy measures were assessed over 12 weeks and included walking pain (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] A1), overall knee pain, WOMAC A, B, C and total score, Patient Global Impression of Change (PGIC), OMERACT-OARSI responder rate and rescue medication use. Adverse events (AEs) were monitored up to 24 weeks.ResultsThe primary efficacy endpoint was met with a between-group difference of -7.49 (VAS 0-100) on WOMAC A1 changes over 4 weeks (P < 0.05 favoring GZ389988A). The secondary outcome on WOMAC A1 changes over 12 weeks had a between-group difference of -6.78 (P = 0.064). Among weekly assessments, statistically significant greater improvement in the GZ389988A group was observed in WOMAC A1, overall knee pain and/or WOMAC A at weeks 2-5. Although not statistically significant, improvements over placebo on pain and WOMAC C persisted over 12 weeks. Greater AE incidence was observed in the GZ389988A group including transient and self-limited injection joint inflammatory reactions with a spike of acetaminophen intake within the first week post-injection.ConclusionIA injection of TrkA inhibitor GZ389988A in knee OA subjects reduced pain with a numerically functional gain and an acceptable safety profile. (ClinicalTrials.gov, NCT02845271).Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

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