Randall M. Stevens
A single 1-mg injection of trans-capsaicin, a synthetic treatment based on the extract that gives chili peppers their signature spice, significantly reduced osteoarthritis-associated knee pain through 24 weeks, with a safety profile similar to placebo, according to data published in Arthritis & Rheumatology.
“CNTX-4975, or trans-capsaicin, works in a way that is different to existing therapies — it does not have to be continuously present in the joint to produce a significant, long lasting analgesic effect,” Randall M. Stevens, MD, of Centrexion Therapeutics, told Healio Rheumatology. “The intra-articular doses of CNTX-4975 used in this study were able to deliver sufficient trans-capsaicin locally to do this before leaving the joint. We know that after intra-articular injection of CNTX-4975, it is rapidly cleared from the body with systemic levels of drug being detectible for less than 24 hours.”
To analyze the safety and efficacy of a single dose of CNTX-4975 in patients with chronic moderate-to-severe knee pain linked to OA, Stevens and colleagues conducted the phase 2b, double-blind TRIUMPH study. The researchers recruited participants from 22 sites in the United States, including adults aged 45 to 80 years with stable OA-associated knee pain for at least 2 months. Participants were randomly selected, in a 2:1:2 ratio, to receive a single, intraarticular injection of either 0.5 mg of CNTX-4975, 1 mg of CNTX-4975 or placebo.
A single 1-mg injection of trans-capsaicin significantly reduced OA-associated knee pain through 24 weeks, according to data.
The primary endpoint was area under the curve for change in daily pain, measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Question A1 (QA1), with a walking score ranging from zero to 10, from baseline through week 12. A total of 175 participants were included in the safety analysis, including 70 who received placebo, 34 treated with 0.5 mg of CNTX-4975 and 71 who received 1 mg.
The efficacy analysis included 172 participants, of whom 69 received placebo, 33 received 0.5 mg of CNTX-4975 and 70 received 1 mg.
According to the researchers, by week 12, there were greater decreases in area-under-curve pain in patients treated with either dose of CNTX4975 than in those who received placebo. Least squares mean differences were –0.79 for participants who received 0.5 mg of the treatment (P = .074) and –1.6 for those treated with 1 mg (P < .0001). Participants who received 1 mg of CNTX-4975 demonstrated significant improvements that were maintained at week 24, with a least squares mean difference of –1.4 (P = .0002). Adverse events associated with the treatment were similar among patients in the placebo and 1mg groups.
“Patients with moderate to severe pain from knee OA, including moderate to severe radiographic damage, with a BMI up to 45kg/m2 and have failed prior treatment, can, from a single 1-mg CNTX-4975 intra-articular injection, have substantial reduction in pain and 49% to 60% improvement in knee stiffness and function,” Stevens said. “This has onset by the second day and a duration of benefit of up to 6 months, all while having a side effect profile that is similar to placebo.” – by Jason Laday
Disclosure: Stevens reports employment with Centrexion Therapeutics, which sponsored this study. Please see the study for all other relevant financial disclosures.