# A randomized, double-blind, placebo-controlled and dose-ranging study to evaluate the safety and efficacy of XG005 in subjects with painful osteoarthritis of the knee

## TL;DR

This study tested XG005, a new non-opioid treatment for knee osteoarthritis, and found it effective in reducing pain and improving function with mild side effects.

## Contribution

XG005 is a novel dual-mechanism agent targeting both inflammatory and neuropathic pain in osteoarthritis.

## Key findings

- XG005 750 mg significantly reduced walking pain compared to placebo after 4 weeks.
- Patients with neuropathic pain showed 2-3 times greater improvement than those with nociceptive pain.
- XG005 improved multiple OA-related outcomes with mild side effects like dizziness and somnolence.

## Abstract

Symptomatic treatment for osteoarthritis (OA) remains a major unmet need. This trial evaluated XG005, a novel, non-opioid, dual-mechanism agent targeting both inflammatory and neuropathic pathways in patients with knee OA.

This randomized, double-blind, placebo-controlled study enrolled 318 patients with moderate-to-severe knee OA pain to receive XG005 750 mg, 500 mg, or placebo twice daily for 4 weeks. Efficacy measures included weekly average of daily walking pain (WADWP), Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Patient Global Impression of Change (PGIC), Sleep Interference Score (SIS), and Short-Form-12 Health Survey (SF-12).

The primary efficacy endpoint of improvement from baseline in WADWP at week 4 was statistically greater for the 750 mg group than placebo with least squares mean difference (LSMD) (95 % CI) of −0.55 (−0.94, −0.16). Key secondary endpoints were significantly improved for high- and low-dose XG005 compared to placebo at week 4, with LSMD (95 % CI) of −0.43 (−0.74, −0.13) and −0.4 (−0.78, −0.02) in WOMAC pain, and 5.56 (2.69, 8.42) and 3.74 (0.17, 7.31) in KOOS pain. WOMAC and KOOS stiffness and function, PGIC, SIS and SF-12 mental and general health showed statistically significant improvements over placebo. Patients with neuropathic pain had approximately 2-3-fold greater symptom improvements than patients with nociceptive pain. Mild dizziness and somnolence were most seen in XG005 groups.

XG005 demonstrated consistent efficacy in improving OA symptoms with acceptable tolerability. Additional studies in OA patients with neuropathic pain are needed to confirm its dual mechanism advantages.

CTR20222406.