OP0137 OPTIMIZING SUBJECT SELECTION IN KNEE OSTEOARTHRITIS CLINICAL TRIALS BY RADIOGRAPHIC JOINT SPACE WIDTH: POST-HOC CLINICAL RESPONSE ANALYSIS FROM A PHASE 2B TRIAL OF WNT PATHWAY INHIBITOR, SM04690

Abstract

Background Knee osteoarthritis (OA) trial radiographic inclusion criteria usually comprises Kellgren-Lawrence (KL) grading, which mixes features such as osteophytes and joint space narrowing and leads to study population heterogeneity. Selecting subjects with baseline medial joint space width (mJSW) 2-4 mm has been shown to reduce heterogeneity and improve responsiveness to radiographic change in comparison to broader knee OA populations.1,2 However, effects of baseline-fixed mJSW on symptom responsiveness are unknown. Objectives To evaluate the impact of baseline mJSW 2-4 mm on patient-reported outcomes (PROs) as measured by effect size in a 24-week phase 2b trial of SM04690, a Wnt pathway inhibitor in development as a potential disease-modifying OA drug (DMOAD). Methods Knee OA subjects with KL grades 2-3 and Pain Numerical Rating Scale (NRS, [0-10]) ≥4 and ≤ 8 in the target knee and Results 635 subjects (91.4%) completed the study (mean age 59.0 [±8.5] years, BMI 29.0 [±4.0] kg/m2, female 58.4%, KL3 57.3%). In both full analysis set (FAS, all dosed subjects) and mJSW 2-4 mm subjects, significant improvements compared to PBO (P Conclusion In this post-hoc analysis of SM04690-treated knee OA subjects, those with baseline mJSW 2-4 mm showed increased PRO effect sizes compared to those in the FAS. Previous data also demonstrated SM04690-treated subjects with mJSW 2-4 mm had improved radiographic sensitivity to change. Data from SM04690 studies suggest mJSW 2-4 mm should be considered as an inclusion criterion for trials of potential knee DMOADs. Image: Schematic representation of SM04690’s proposed mechanism of action via CLK2 and DYRK1A inhibition in OA References [1] Bowes M, et al. ARD2017 [2] Yazici Y, et al. Arthritis Rheumatol. 2017 [3] Yazici Y, et al. Arthritis Rheumatol. 2018 Disclosure of Interests Sarah Kennedy Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Christopher Swearingen Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Jeyanesh Tambiah Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Philip G Conaghan Consultant for: Flexion Therapeutics, AbbVie, Medivir, Merck Serono, Novartis, GlaxoSmithKline