Full Papers
A Phase 3, 28-week, multicentre, randomised, double-blind, placebo-controlled trial (OA-10) to evaluate the efficacy and safety of a single injection of lorecivivint in the target knee joint of moderately to severely symptomatic osteoarthritis patients
Y. Yazici1, J.R. Tambiah2, C.J. Swearingen3, V.A. Lopez4, S. Kennedy5, M.S. Fineman6, I. Simsek7, E. Solomon8, T.E. Mcalindon9
- Biosplice Therapeutics, Inc. San Diego, CA, and NYU Grossman School of Medicine, New York, NY, USA. yusuf.yazici@biosplice.com
- Biosplice Therapeutics, Inc. San Diego, CA, USA.
- Biosplice Therapeutics, Inc. San Diego, CA, USA.
- Biosplice Therapeutics, Inc. San Diego, CA, USA.
- Biosplice Therapeutics, Inc. San Diego, CA, USA.
- Biosplice Therapeutics, Inc. San Diego, CA, USA.
- Biosplice Therapeutics, Inc. San Diego, CA, USA.
- Biosplice Therapeutics, Inc. San Diego, CA, USA.
- UMass Chan Medical School and UMass Memorial Medical Center, Boston, MA, USA.
CER17634
Full Papers
PMID: 39808288 [PubMed]
Received: 03/03/2024
Accepted : 02/12/2024
In Press: 13/01/2025
Abstract
OBJECTIVES:
To assess the efficacy and safety of an intra-articular (IA) CLK/DYRK inhibitor, lorecivivint (LOR), for the treatment of moderate to severe symptomatic knee osteoarthritis (OA).
METHODS:
This was a Phase 3, 28-week, multicentre, double-blind, placebo-controlled study evaluating the efficacy and safety of a single IA injection of LOR. Patients with ACR-defined knee OA, Kellgren-Lawrence (KL) grades 2–3, and pain Numeric Rating Scale (NRS) ≥4 and ≤8 in the target knee were randomised (1:1) to receive LOR 0.07 mg or vehicle placebo (PBO) on Day 1. The primary endpoint was the change from baseline in Pain NRS at Week 12 between LOR and PBO. Additional outcomes included the change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Function, WOMAC Pain, Patient Global Assessment and safety.
RESULTS:
498 patients were randomised, and 51.9% had KL Grade 3 severity. In the full analysis set (FAS), LOR failed to meet the primary endpoint when compared to PBO. No significant treatment differences were noted in other efficacy endpoints. A post-hoc analysis demonstrated a positive treatment effect of LOR relative to PBO in the KL Grade 2 subgroup; the difference in weekly Pain NRS between LOR and PBO groups showed nominal statistical significance at Week 4 (p<0.05). Incidences, seriousness, and severity of adverse events were similar across the treatment groups.
CONCLUSIONS:
LOR was well tolerated despite not meeting the primary endpoint. Efficacy signals were identified in patients with less severe structural knee OA disease, suggesting earlier intervention may be more effective.
