Clinical Benefit Of Cntx-4975 Intra-articular Injection For Moderate To Severe Osteoarthritis Knee Pain

PURPOSE: To evaluate the effect of CNTX-4975 intra-articular (IA) injection on pain, function, and quality of life (QoL) in subjects with knee osteoarthritis (OA). METHODS: A phase 3, open-label, 8-wk study (NCT03661996) enrolled subjects aged 40–95 y with stable, moderate to severe OA knee pain in the index knee (average pain 24 h) after ≥2 failed therapies. Subjects were assigned to unilateral/bilateral CNTX-4975 1 mg IA injections as determined by OA pain/joint replacement status (Table) and randomized by site to 1 of 5 joint cooling/injection regimens to evaluate procedure experience. The circumferential joint cooling wrap used in the phase 2 pivotal trial was compared with 4 circumferential gel-pack wrap cooling groups with varying cooling schedules/injection techniques. Outcomes assessed through wk 8 included average daily index knee pain with walking (numeric pain rating scale [NPRS], 0 [no pain] to 10 [worst pain]) and Knee Injury OA Outcomes Score (KOOS) subscales (range, 0–100; higher is improvement; Table). Least squares (LS) mean, 95% CI, and P value were calculated for change from baseline in NPRS and KOOS scores using a mixed model for repeated measures. RESULTS: The intent-to-treat population included 848 subjects; baseline NPRS index knee pain with walking scores (mean [SD]) by subject type: A, 6.5 (1.50); B, 7.4 (1.35); C, 6.2 (1.21). By day 3, NPRS scores were significantly (P<0.0001) improved; LS mean (SE [95% CI]): A, −3.98 (0.170 [−4.32, −3.64]); B, −4.21 (0.103 [−4.41, −4.01]); C, −3.71 (0.375 [−4.48, −2.94]). Improvement was maintained at wk 8; A, −3.48 (0.191 [−3.86, −3.10]); B, −4.02 (0.118 [−4.25, −3.79]); C, −3.52 (0.416 [−4.38, −2.67]); all P<0.0001. All KOOS subscale scores were significantly improved at wk 8 (Table). CONCLUSIONS: Subjects with moderate to severe knee OA pain showed significant clinical improvements as early as 3 days and through 8 wks post injection in knee pain, function, and QoL after a single CNTX-4975 1 mg IA injection.