Background: Osteoarthritis (OA) is a severe, chronic, debilitating condition. Recent advances in the mechanistic understanding of the pathogenesis of OA highlight the role of inflammatory involvement, and particularly a key role for macrophages in the propagation of OA articular damage. Allocetra ^TM is an innovative allogeneic cellular therapy that immune modulates the function of activated macrophages to reset inflammatory balance, by harnessing the naturally occurring property of apoptotic cells to induce an immuno-modulated pro-homeostatic state. An ongoing double blind, randomized, multi-center clinical trial is evaluating the safety and efficacy of Allocetra ^TM intra-articular (IA) injections for knee OA.

Objectives: The clinical trial aims to evaluate the safety and efficacy of intra-articular administration of Allocetra ^TM in patients with symptomatic knee OA.

Methods: This is a double blind, randomized, multi-center study to evaluate the safety and efficacy of intra-articular administration of Allocetra ^TM compared to placebo in patients with symptomatic knee OA. Patients had chronic knee OA with radiographic classification of Kelgren-Lawrence grade 2-3. The first stage of the study is an open label, multiple dose safety run-in Phase I. Patients with knee OA were treated with three IA injections of Allocetra ^TM in escalating doses. Patients were followed for safety assessment following injections, and responses to treatment were assessed by self reporting of pain (numerical rating scale (NRS) 0-10) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaires. Responses to treatment were assessed in accordance with the OMERACT-OARSI responder criteria. The second stage of the study is a randomized controlled comparative Phase II evaluation of the safety and efficacy of Allocetra ^TM IA injection in comparison to placebo.

Results: Fifteen patients were treated with Allocetra ^TM in the Phase I stage of the study. All patients had symptomatic disease, with knee pain NRS at baseline average of 6.3 (95% CI: 5.6-7.0). All patients received three IA Allocetra ^TM injections at intervals of 2-4 weeks between doses, apart from one patient who received 2 injections. Patients were assessed weekly for pain NRS, and at 3 months for WOMAC pain, stiffness and function. To date, all patients completed at least 3 months of assessment following the last injection, with an average 52.4% (95% CI: 35.1-69.7) reduction of reported pain, compared to the pain level at baseline. The reported reduction in pain was consistent with the results of the WOMAC questionnaire at 3 months following the last treatment, demonstrating a total reduction of 46.0% (95% CI: 31.4-60.5), with 45.4% (95% CI: 30.2-60.6) improvement in functionality. In total, 80% of the patients qualified as responders per the OMERACT-OARSI responder criteria. No serious adverse events were reported. Patients reported transient events of discomfort/pain or swelling in the knee following injection, mostly mild in severity.

Conclusion: A characterization of safety of Allocetra ^TM IA injections for knee OA indicates a favorable safety profile with good compliance to repeat injections and initial promising efficacy results. Transient injection reactions were mostly mild, with no observed dose relationship of injection reactions, allowing a recommendation by the independent safety committee to proceed to the randomized phase of the study with the highest Allocetra ^TM dose tested. Initial indications of efficacy were observed in the majority of the patients, demonstrated as marked reductions in pain reported and an improvement in functionality following treatment, compared to baseline.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Einat Galamidi Enlivex Therapeutics Ltd., Bernt Husøy: None declared, Nabil Ghrayeb: None declared, Amir Oron: None declared, Ori Elkayam: None declared, Muhammad Khatib: None declared, Asger R. Bihlet: None declared, Lior Binder Enlivex Therapeutics Ltd., Lital Weinfeld-Bergman Enlivex Therapeutics Ltd., Dror Mevorach Enlivex Therapeutics Ltd., Oren Hershkovitz Enlivex Therapeutics Ltd.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.