People with knee osteoarthritis (OA) pain that are participating in a clinical trial of CNTX-4975 are getting some promising results so far.
In the randomized, double-blind, placebo-controlled, multicenter TRIUMPH study, CNTX-4975, met its primary endpoint of a reduction in pain with walking through 12 weeks with high statistical significance and demonstrated a duration of effect of at least 24 weeks after a single dose. At the 1.0 mg dose, two-thirds of patients achieved 50 percent or greater reduction in pain and nearly one-quarter of patients achieved a 90 percent or greater reduction in pain
“As our population ages, chronic osteoarthritis pain is an important and growing problem. Short of joint replacement which carries risks associated with any surgery, there are insufficient options and severe osteoarthritis pain is one of the most common reasons patients take opioids,” said Nathaniel Katz M.D., M.S., adjunct associate professor of anesthesia at Tufts University School of Medicine.
“It is critical to develop effective non-opioid therapies that can avoid the abuse and addiction issues associated with opioid treatments and CNTX-4975 represents an important new approach for pain relief for patients. The results seen in this clinical trial suggest that the medicine warrants further clinical investigation,” Dr. Katz added.
“We are very encouraged by the extent and duration of pain relief treatment seen with CNTX-4975, particularly at the 1.0 mg dose. We look forward to discussing these results with the FDA and initiating Phase 3 development of CNTX-4975 next year,” said Randall M. Stevens, M.D., chief medical officer for Centrexion Therapeutics, the manufacturer of the therapy.
CNTX-4975 is a synthetic form of trans-capsaicin (a medicine traditionally derived from the chili plant. It’s designed to be injected directly into the site of pain to provide rapid onset, large reduction and long duration of relief from moderate to severe pain without affecting touch sensibility or position sense.
It works by selectively targeting the capsaicin receptor (TRPV1) to rapidly inactivate only the local pain fibers transmitting signals to the brain. This approach provides pain relief that can last for months until the ends of the local pain fibers regenerate, while leaving the rest of the nerve fiber functioning as normal, and without the risks of toxicities of NSAIDs and injected steroids or the side effects, including abuse and addiction, associated with opioid treatments.
The dose-ranging Phase 2b study evaluated the safety and efficacy of CNTX-4975 in 175 patients with chronic moderate to severe knee OA pain over 24 weeks. Patients were randomized to receive either a single injection into the knee of CNTX-4975 0.5 mg (n=34), CNTX-4975 1.0 mg (n=71) or placebo (n=70). The primary endpoint was pain with walking (WOMAC [Western Ontario and McMaster Universities Arthritis Index] A1) at Week 12.
Secondary outcome measures included knee joint stiffness and function (both assessed by WOMAC B and WOMAC C, respectively), patient global impression of change (PGIC), responder analysis (the proportion of patients improved by percent from baseline pain), and safety and tolerability. Additional follow-up to 24 weeks was conducted to assess the duration of response from a single injection.
Results through 12 weeks showed that both doses of CNTX-4975 were significantly more effective than placebo in the primary endpoint of pain with walking. For the 1.0 mg dose:
- Both weekly pain and daily pain measures were highly statistically significant (p<0.001)
- Twenty-two percent of patients achieved a 90 percent or greater reduction in pain and 67 percent of patients achieved 50 percent or greater reduction in pain
- CNTX-4975 was significantly more effective than placebo in the secondary outcome measures of stiffness, function and PGIC at every time point
- The onset of pain reduction occurred within days and reached statistical significance at Week 1
- Maximum effect was seen at Week 5 and a stable, statistically significant response at every time point was observed through Week 12
Through 24 weeks with the 1.0 mg dose, the study met the endpoint of duration of response with statistical significance with a single dose of CNTX-4975 compared to placebo.
Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 14 million people in the United States. It occurs when the protective cartilage on the ends of the bones wears down over time, and the bone around the joints harden and form edges. These changes cause pain, swelling and problems moving the joint. OA also causes an inflammatory process to occur in the affected joint, further damaging the cartilage.