POS1351 A PHASE 2, 104-WEEK STUDY OF REPEAT LORECIVIVINT INJECTIONS EVALUATING SAFETY, EFFICACY, AND BONE HEALTH UTILIZING QUANTITATIVE COMPUTED TOMOGRAPHY (QCT) IN KNEE OSTEOARTHRITIS (OA-06)

Abstract

Background/purpose: Knee osteoarthritis (OA) is a common painful joint disorder. Lorecivivint (LOR), an intra-articular (IA) CLK/ DYRK inhibitor thought to modulate Wnt and inflammatory pathways, is a potential knee OA treatment. The primary objective of this 104-week trial was to assess the safety of repeat 6-month LOR dosing (OA-06, NCT03727022) while characterizing juxta-articular and regional bone health. Methods: Participants with ACR-defined OA, aged 40-80, and Kellgren-Lawrence (KL) grades 2-3 were randomized 1:1 to receive 2 mL IA injections 0.07 mg LOR or placebo (PBO) at 6-month intervals (4 injections total). The trial was conducted in two 52-week phases, part A (week 0-52) and part B (week 53-104). General safety was assessed by physical examinations, clinical laboratory tests, collection of adverse events (AEs), and serious AEs (SAEs). Bone safety was assessed by quantitative computed tomography (qCT) with phantom calibration to assess BMD in target and non-target knees, bone and cartilage biomarkers, and dual energy x-ray absorptiometry (DXA) to assess spine and hip BMD. Exploratory efficacy was assessed by patient-reported outcomes (PROs). For bone imaging endpoints, change from baseline was estimated using baseline-adjusted ANCOVA. Results: 101 participants (mean 60.9 ± 9.1 years, BMI 28.6 ± 3.7 kg/m2, female 59.4%, KL2 52.5%) enrolled. Baseline imbalances existed in sex (PBO 68.0% vs. LOR 51.0% female), KL grade (PBO 62.0% vs LOR 42.1% KL 2), and site randomization. 77 participants completed part A and 53 completed part B. AE rates were similar between PBO and LOR, and no SAEs were deemed treatment related. There were no bone health clinical signals, with no fractures, accelerated OA, or osteoporosis. Observed target knee qCT BMD values were similar between LOR and PBO (Fig. 1). Repeated injection did not appear to affect BMD rate of change. No meaningful differences were seen in target knee BMD in female and age [65-80], nor in total hip or spine BMD between the LOR and PBO treatment. There were no meaningful differences in PRO between LOR and PBO. Conclusions: The incidence of AEs was similar between treatment groups and not affected by repeated injections of LOR. Multiple injections of LOR over 2 years did not appear to lead to any bone health adverse effects locally around the knee or regionally at spine or hip. (Figure Presented).