161 Evaluation of intra-articular CNTX-4975 (highly purified, synthetic trans-capsaicin) for knee OA pain in patients with radiographic presence of OA in the opposite knee

Background: This TRIUMPH study post-hoc analysis evaluated the efficacy and safety of CNTX-4975 in subjects with unilateral knee pain with/without radiographic evidence of OA in the opposite knee.

Methods: Subjects aged 45-80 years with chronic knee OA and stable moderate to severe knee OA pain in one knee (index knee; non-index knee, no to mild pain) who failed oral/intra-articular therapies were randomized 2:1:2 to a single intra-articular injection of placebo, CNTX-4975 0.5 mg, or CNTX-4975 1.0 mg. Randomization was stratified by Kellgren-Lawrence (K-L) grade (2-3 vs 4) and body mass index (<30 vs ⩾ 30 kg/m²). Unilateral OA was defined as K-L grade 0, 1, or missing in the non-index (untreated) knee; bilateral OA, grades 2-4 in both knees. Area under the curve was assessed for change from baseline in WOMAC QA1, pain with walking on a flat surface, daily through week 12 and weekly through week 24. Weekly WOMAC B and C scores were also analysed. Statistical tests were 2-sided (alpha, 0.10). Safety assessments included treatment-emergent adverse events (TEAEs).

Results: Safety analysis comprised 175 subjects; unilateral knee OA, n = 52 (placebo, n = 17; CNTX-4975: 0.5 mg, n = 18; 1.0 mg, n = 17) and bilateral knee OA, n = 123 (placebo, n = 53; 0.5 mg, n = 16; 1.0 mg, n = 54). Efficacy analysis included 172 subjects (3 in bilateral group excluded before unblinding). Mean baseline WOMAC QA1 pain score (index knee) was 7.3 (numeric rating scale, 0-10) in the unilateral and bilateral groups. WOMAC QA1 scores improved with CNTX-4975 1.0 mg vs placebo in the unilateral (week 12, P=0.0004; week 24, P=0.0017) and bilateral groups (week 12, P=0.0053; week 24, P=0.0170); other results shown in the Table. Incidence of TEAEs was similar between unilateral and bilateral groups through week 24 (35% vs 33%). TEAEs were mild to moderate; most were determined unrelated to study treatment.

161 Table 1:

Mean Changes From Baseline in Average Western Ontario and McMaster Universities Osteoarthritis

	CNTX-4975 0.5 mg				CNTX-4975 1.0 mg
	Unilateral (n = 18)		Bilateral (n = 15)		Unilateral (n = 17)		Bilateral (n = 53)
Endpoint	Week 12	Week 24	Week 12	Week 24	Week 12	Week 24	Week 12	Week 24
WOMAC QA1 LSMD vs placebo 90% CI P value	−1.1 (−2.2, 0.0) 0.1013	−0.9 (−2.0, 0.3) 0.2106	−0.9 (−2.0, 0.3) 0.2106	−0.4 (−1.4, 0.6) 0.5058	−2.6 (−3.7, −1.5) 0.0004	−2.3 (−3.4, −1.1) 0.0017	−1.2 (−1.9, −0.5) 0.0053	−1.0 (−1.7, −0.3) 0.0170
WOMAC B LSMD vs placebo 90% CI P value	−0.9 (−2.8, 1.0) 0.4439	−1.2 (−3.3, 0.90) 0.3403	−0.8 (−2.4, 0.9) 0.4407	−0.6 (−2.3, 1.2) 0.6042	−2.9 (−4.8, −1.1) 0.0098	−3.2 (−5.2, −1.2) 0.0117	−1.3 (−2.4, −0.3) 0.0422	−1.5 (−2.7, −0.3) 0.0376
WOMAC C LSMD vs placebo 90% CI P value	−3.0 (−18.5, 12.5) 0.7452	−4.1 (−21.8, 13.6) 0.6976	−4.5 (−17.7, 8.8) 0.5762	−4.1 (−18.6, 10.4) 0.6398	−21.4 (−36.8, −6.0) 0.0243	−23.3 (−40.9, −5.7) 0.0311	−11.3 (−20.2, −2.4) 0.0375	−11.3 (−21.0, −1.5) 0.0575

AUC, area under the curve; LSMD, least squares mean difference; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index. AUC using analysis of covariance in modified intent-to-treat population. Week 12 data for WOMAC QA1 are daily values; all other data are weekly averages. WOMAC 11-point numeric rating scale: 0 (none) to 10 (extreme); WOMAC B dimension score is the sum of the 2 stiffness subscale responses (range, 0 to 20); WOMAC C dimension score is the sum of the 17 function subscale responses (range, 0 to 170).

Conclusion: CNTX-4975 1.0 mg significantly improved pain with walking and subject-reported knee stiffness and physical function vs placebo in the index knee and was well tolerated. Greater absolute improvements were seen in subjects with unilateral vs bilateral knee OA, although the non-index knee had no to mild pain at baseline.

Disclosures: R. Stevens: Corporate appointments; Employee of Centrexion Therapeutics Corp. J. Campbell: Corporate appointments; Employee of Centrexion Therapeutics Corp. K. Guedes: Corporate appointments; Employee of Centrexion Therapeutics Corp. V. Smith: Corporate appointments; Employee of Premier Research. P. Hanson: Corporate appointments; Employee of Centrexion Therapeutics Corp.