New drug effective, well tolerated in patients with osteoarthritis knee pain
In patients with moderate to severe osteoarthritis knee pain, a single intra-articular injection of 1 mg of CNTX-4975 was well tolerated and significantly improved pain with walking, knee stiffness and physical function, according to findings presented at PAINWeek.
“As our populations are aging, the number of people suffering from moderate to severe knee osteoarthritis is increasing,” Randall M. Stevens, MD, chief medical officer of Centrexion Therapeutics, told Healio Internal Medicine. “Unfortunately, current treatments — like NSAIDs, opioids or hyaluronic acid and corticosteroid injections — are limited in the level of efficacy they provide, and come with significant side effects that can be serious, especially in older individuals. CNTX-4975 for intra-articular injection has shown substantial promise in clinical trials as a long-lasting and efficacious treatment, with a safety profile that looks similar to that of placebo.”
Stevens and colleagues conducted a phase 2 dose-ranging study to evaluate the efficacy and safety of CNTX-4975 in 172 patients aged 45 to 80 years with stable, chronic, moderate to severe osteoarthritis knee pain who failed previous oral/intra-articular analgesics. Patients were randomized 2:1:2 to receive either a single intra-articular injection of placebo (n = 69), 0.5 mg of CNTX-4975 (n = 33) or 1 mg CNTX-4975 (n = 70). They were randomly assigned by Kellgren-Lawrence (K-L) grade (2-3 vs. 4) and BMI (<30 vs. 30 kg/m²).
The primary efficacy endpoint was the change from baseline through week 12 in the area under the curve in daily Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Question A1 score, ranging from 0 (no pain with walking) to 10 (extreme pain with walking). For this endpoint, the researchers calculated the least squares mean differences (LSMD) for placebo vs. CNTX-4975. Treatment-emergent adverse events and laboratory evaluations were assessed to measure safety.
Results showed that the mean baseline WOMAC Question A1 score was 7.3. Compared with placebo, 0.5 mg of CNTX-4975 (LSMD, 0.8; P = .07) and 1 mg of CNTX-4975 (LSMD, 1.6; P < .0001) improved WOMAC A1 scores at week 12, as did 1 mg of CNTX-4975 (LSMD, 1.4; P = .0002) at week 24. Numerically greater improvements in WOMAC A1 score were seen in the K-L 2-3 subgroup treated with 0.5 mg of CNTX-4975 compared with placebo (LSMD, 0.7; P = .11), while significant improvements in WOMAC A1 score were observed in those treated with 1 mg of CNTX-4975 compared with placebo (LSMD, 1.7; P < .0001).
In addition, a difference between placebo and 1 mg of CNTX-4975 was observed among patients with K-L grade 4 (LSMD, 3.4; P = .07). A total of 33% of patients treated with placebo, 58% of patients treated with 0.5 mg of CNTX-4975 and 61% of patients treated with 1 mg of CNTX-4975 had a greater than or equal to 50% reduction in WOMAC A1 score at week 12.
At week 24, 30% of patients in the placebo and CNTX-4975 1 mg groups experienced treatment-emergent adverse events compared with 47% of those in the CNTX-4975 0.5 mg group. Arthralgia was the most frequent adverse event for placebo (5.7%) and CNTX-4975 1 mg (7%).
“The treatment provides an onset of effect within 1 week, with an average of severe pain at baseline improving to no to mild pain at 12 weeks after treatment. Additionally, we’ve seen improvement in knee function and stiffness by about 50% at 12 weeks,” Stevens said in an interview. “This benefit is greatest at 12 weeks, but clinically meaningful improvement continues to 24 weeks. The expected dosing is every 6 months to maintain efficacy, so we’re optimistic that patients will not only see an improvement in pain and function, but also in their quality of life, as they are able to more easily perform everyday tasks, like climbing stairs or returning to work.” – by Alaina Tedesco
Stevens RM, et al. Efficacy and safety of CNTX-4975 in subjects with moderate to severe osteoarthritis knee pain: A 24-week, randomized, double-blind, placebo-controlled, dose-ranging study. Presented at: PAINWeek 2017; Sept. 5-9; Las Vegas.
Disclosure: Healio Internal Medicine was unable to confirm relevant financial disclosures at the time of publication.