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Highly purified synthetic trans-capsaicin (CNTX‐4975) injected directly into the joint reduced pain in chronic knee osteoarthritis (OA), data from the open-label phase III trial showed.

People with bilateral knee OA pain who received the investigational treatment had less pain when walking in as early as 3 days and the effect was maintained for 8 weeks, reported Randall Stevens, MD, of Centrexion Therapeutics in Boston, at the American Society of Interventional Pain Physicians (ASIPP) virtual meeting.

The findings supported those of the phase II study, which showed that a single 1-mg injection of CNTX-4975 provided a significant (P<0.0001) and clinically meaningful , with effects persisting for up to 24 weeks.

Because intraarticular capsaicin injection produces short-term procedural pain, VICTORY-3 aimed to assess different ways to administer CNTX-4975, in addition to looking at the drug's clinical benefit on bilateral knee pain.

Earlier reports showed that cooling the knee with a circumferential wrap -- either a circulating ice water wrap or an ice gel pack wrap -- reduced intra-articular temperature much better than an ice bag on the knee, Stevens said. "The result was the short-lived post-injection pain was cut by 50%, compared to an ice bag," he told 乌鸦传媒.

VICTORY-3 showed that "either method of circumferential cooling wrap -- ice water or gel-based -- was equivalent in effect to each other," he added. "It also showed that using two needles to inject lidocaine and capsaicin, separated by 30 minutes, was no better than cooling and using one needle to inject first lidocaine, then capsaicin, to manage post-injection pain."

Capsaicin products currently are used in topical applications to treat OA, including an 8% capsaicin patch, Stevens noted.

CNTX-4975 works by targeting the capsaicin receptor (TRPV1) to selectively inactivate local pain fibers transmitting signals to the brain, providing pain relief that may last for months until the ends of the fibers regenerate. The compound has a short half-life and is cleared from the body within 24 hours.

Pain from knee OA "may be effectively and safely managed with this new investigational compound, CNTX‐4975, and is thought to be mediated by sustained desensitization of nociceptors," observed Jack Cush, MD, of Baylor University Medical Center in Dallas, who wasn't involved with the research.

In the 8-week VICTORY-3 study, 848 people with moderate to severe OA knee pain received unilateral or bilateral CNTX-4975 1 mg intra-articular injections. About 60% of participants were female. The average age of participants was about 63 and mean BMI was 31.3. Most had bilateral radiographic OA (81.7%) and index knee grades 2–4 (87.4%).

A total of 523 participants had bilateral pain and received bilateral capsaicin intra-articular injections: 427 received injections in both knees, and 96 did not receive an injection in the non-index knee. Mean baseline scores for pain with walking were 7.4 in the index knee and 6.1 in the non-index knee on the 10-point Numerical Pain Rating Scale (NPRS), where 0 represents no pain and 10 represents worst pain ever.

Reductions in pain with walking after CNTX-4975 injections were seen as early as day 3 for the index knee (LS mean change from baseline in NPRS score -4.21, 95% CI -4.41 to -4.01, P<0.0001) and day 8 plus 3 days for the non-index knee (LS mean -3.84, 95% CI -4.02 to -3.65, P<0.0001). Improvements were maintained at week 8 for both knees.

All cooling and administration regimens evaluated in VICTORY-3 were clinically acceptable based on pain and satisfaction scores, Stevens said.

"A single intra-articular injection of CNTX-4975 1 mg into each knee with moderate to severe OA pain may provide a valuable new option for fast and long-lasting relief," he noted.

Pivotal phase III trials of CNTX-4975 are using a proprietary aqueous formulation in a pre-filled syringe of capsaicin, he added. is a 52-week double-blind trial with a single dose at day 1 for painful knee OA; is a 52-week double-blind trial with a first dose at day 1 and second dose at week 26.

Adverse events in VICTORY-3 were not reported at ASIPP, but in TRIUMPH, treatment‐emergent were similar in placebo and CNTX‐4975 groups. CNTX-4975 has been granted FDA for treating moderate-to-severe pain associated with knee OA.

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