Background/Purpose: Nearly 60% of patients with knee OA have unilateral OA; most of those patients develop bilateral OA. CNTX-4975 is a highly purified, synthetic trans-capsaicin that targets transient receptor potential vanilloid 1, producing analgesia via reversible desensitization of primary afferent pain fiber terminals. CNTX-4975 1.0 mg was well tolerated and effective in the phase 2b TRIUMPH study; this post hoc analysis evaluated efficacy and safety in subjects with unilateral knee pain with and without radiographic evidence of OA in the opposite knee.

Methods: Subjects aged 45–80 y with chronic knee OA and stable moderate to severe knee OA pain in 1 knee (index knee; nonindex knee, no to mild pain) who failed oral/IA therapies were randomized 2:1:2 to a single IA injection of placebo, CNTX-4975 0.5 mg, or CNTX-4975 1.0 mg. ACR criteria were met by 89% for knee OA as assessed by knee pain, radiographic findings (Kellgren-Lawrence [K-L] grade 2–4), and age >50 y; 11% had K-L grade 2–4 and were age ≤50 years. Randomization was stratified by K-L grade (2–3 vs 4) and BMI (<30 vs ≥30 kg/m²). Unilateral OA: K-L grade 0, 1, or missing (see Table) in the nonindex (untreated) knee; bilateral OA: grades 2–4 in both knees. Least squares mean differences (P values) for CNTX-4975 groups vs placebo were calculated using a mixed model for repeated measures. WOMAC question A1 (QA1; pain with walking on a flat surface), B (stiffness), and C (physical function) scores were assessed weekly through weeks 12 and 24. Statistical tests were 2-sided (alpha, 0.10). Safety assessments included treatment-emergent adverse events (TEAEs).

Results: The safety analysis comprised 175 subjects: unilateral OA, n=52 (placebo, n=17; CNTX-4975 0.5 mg, n=18; CNTX-4975 1.0 mg, n=17); bilateral OA, n=123 (placebo, n=53; 0.5 mg, n=16; 1.0 mg, n=54). Efficacy analysis included 172 subjects (3 in bilateral subgroup excluded before unblinding). Mean baseline WOMAC QA1 pain score (index knee) was 7.3 (numeric rating scale, 0–10) in each subgroup. WOMAC QA1 scores with CNTX-4975 1.0 mg were significantly improved vs placebo in the unilateral (week 12, P=0.0178; week 24, P=0.0022) and bilateral subgroups (week 12, P=0.0101). WOMAC QA1, B, and C results are in the Table. The incidence of TEAEs for CNTX-4975 1.0 mg was similar to placebo through week 24. All TEAEs were mild to moderate, with most unrelated to treatment.

Conclusion: A single IA injection of CNTX-4975 1.0 mg, the dose used in phase 3 trials, improved pain with walking, knee stiffness, and physical function vs placebo in the index knee and was well tolerated in subjects with moderate to severe unilateral or bilateral knee OA. Greater absolute improvements in WOMAC QA1, B, and C were seen in unilateral versus bilateral knee OA, though the nonindex knee had no to mild baseline pain.