In patients with osteoarthritis (OA), intra-articular injections with trans-capsaicin (CNTX-4975) reduced knee pain in a dose-dependent manner through 24 weeks, according to a report published in Arthritis & Rheumatology.
Pain control options for knee OA can be limited; pharmacologic agents are effective but carry adverse event risk, and joint replacement surgery offers long-term efficacy but comes with serious risks and may not completely alleviate pain and disability. Therefore, there is an unmet need for effective pain management in this population.
The TRIUMPH study (ClinicalTrials.gov identifier: NCT02558439) was a phase 2b, multicenter, randomized, double-blind, placebo-controlled trial that enrolled 175 participants (mean age, 60 years; 63% women) between August 2015 and April 2016 to evaluate the safety and efficacy of single intra-articular CNTX-4975 injections in patients aged 45 to 80 years with stable, chronic, moderate to severe OA-associated knee pain, who had not responded to prior treatments. Participants were randomly assigned to receive placebo (n=70), CNTX-4975 0.5 mg (n=34), or CNTX-4975 1.0 mg (n=71).
The primary outcome was the area under the curve (AUC) representing the change from baseline through 12 weeks of flat-surface pain with walking on a 0 to 10 scale, which was reported daily using question A1 of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC QA1). Secondary outcomes were AUC analysis through 24 weeks and safety assessments. Significance was set at P ≤.10, and least squares mean difference (LSMD) between treatment and placebo was calculated.
There were 172 individuals (n=69 for placebo; n=33 for CNTX-4975 0.5 mg; n=70 for CNTX-4975 1.0 mg) included in the final analysis, with 157 (90%) completing the trial. At baseline, mean WOMAC QA1 pain scores were 7.4, 7.2, and 7.2 for the placebo, 0.5-mg, and 1.0-mg groups, respectively. After 12 weeks, AUC pain was significantly reduced in both the 0.5 mg (LSMD, −0.79; 90% CI, −1.5 to −0.06; P =.0740), and 1.0 mg (LSMD, −1.6; 90% CI, −2.2 to −1.0; P <.0001) treatment groups compared with placebo. After 24 weeks, the 1.0-mg group still demonstrated significant improvements (LSMD, −1.4; 90% CI, −1.9 to −0.77; P =.0002), while the 0.5-mg group did not (LSMD, −0.6; 90% CI, −1.3 to 0.15; P =.19).
Regarding safety, treatment-emergent adverse events were reported in the placebo, 0.5-mg, and 1.0-mg groups at rates of 30%, 47%, and 30%, respectively. Most adverse events in these groups were either mild (19%, 29%, and 20%, respectively) or moderate (11%, 18%, and 10%, respectively), with the 2 most common being arthralgias and upper respiratory infections. Only 1 person in the 0.5-mg group reported a serious treatment-emergent adverse event, with no fatalities. Lab abnormalities were uncommon and were similar in all 3 groups.
Study limitations included small sample size, non-generalizability to the larger knee OA population, and limited safety profile data.
“In conclusion, this study supports the efficacy and safety of the intra-articular injection of trans-capsaicin to manage moderate to severe pain associated with knee osteoarthritis and supports further clinical development,” noted the authors.
This study was sponsored by Centrexion Therapeutics Corp. Several authors disclosed conflicts of interest with Centrexion Therapeutics Corp.
Stevens RM, Ervin J, Nezzer J, et al. Randomized, double‐blind, placebo‐controlled trial of intra‐articular CNTX‐4975 (trans‐capsaicin) for pain associated with osteoarthritis of the knee. Arthritis Rheumatol. doi:10.1002/art.40894