FRI0400 EFFICACY AND SAFETY OF AN INTRA-ARTICULAR INJECTION OF JTA-004, A NOVEL ENHANCED PROTEIN SOLUTION, IN KNEE OSTEOARTHRITIS PAIN: A RANDOMISED, DOUBLE-BLIND CONTROLLED PHASE II/III STUDY
Authors: M. Bettonville, M. Leon, J. Margaux, D. Urbin-Choffray, E. Theunissen, T. Besse-Hammer, Y. Fortems, S. Verlinden, O. Godeaux, A. S. Delmarcelle, J. F. Kaux
Journal: Annals of the Rheumatic Diseases (2020)

Background: Osteoarthritis (OA) is a degenerative, chronic, and progressive joint disease. It is associated with chronic pain, joint function impairments and disabilities, causing a poorer quality of life with physical and/or mental co-morbidity. Along with population ageing and increasing obesity, the incidence of OA is rising and there is an urgent need for new treatment options. Objectives: JTA-004 is a novel protein solution in development for the treatment of knee OA pain. Supplemented with hyaluronic acid and clonidine, it is designed to provide a fast-acting and long-lasting pain relief. To evaluate efficacy and safety and to select the most effective formulation, single intra-articular administration of 3 JTA-004 formulations were tested and compared to Hylan G-F 20 during a 6-month period. Methods: In this prospective, multicentre, double-blind phase II/III trial ( NCT02740231 ), eligible participants were 50-79-year-old men and women with primary knee OA classified with Kellgren-Lawrence grade II or III and a body mass index (BMI) under 35. 164 patients were randomly assigned to one of the three JTA-004 formulations or the reference treatment (Hylan G-F 20) in a 1:1:1:1 ratio. The three JTA-004 formulations differed in their clonidine concentration (50 or 100 µg/ml) and/or their volume of injection (2 or 4 ml) (Table 1). Patients were evaluated using Western Ontario McMaster Universities (WOMAC ® ) scores and Short-Form health survey (SF-12). The primary efficacy endpoint was the change from baseline at 6 months in WOMAC ® VA3.1 Pain Subscale. Safety was assessed by monitoring and reporting vital signs, physical examination, adverse events and concomitant medications throughout the study. Table 1. Description of the three JTA-004 formulations administered JTA-004 formulation Plasma protein solution Clonidine HA Volume of Concentration Amount Concentration Amount Concentration Amount injection JTA-100/2 1.02 g/ml 2.04 g 50 µg/ml 100 µg 10 mg/ml 20 mg 2 ml JTA-200/2 1.02 g/ml 2.04 g 100 µg/ml 200 µg 10 mg/ml 20 mg 2 ml JTA-200/4 1.02 g/ml 4.08 g 50 µg/ml 200 µg 10 mg/ml 40 mg 4 ml Results: At 6 months, patients in the three JTA-004 groups showed a better improvement in pain compared to patients in the reference group. The between-group difference (between each JTA-004 test group and reference group) in adjusted (adapted to difference in baseline values) mean change in WOMAC ® Pain Subscale Score from baseline ranged between -9.49 mm and -11.63 mm at 6 months post-injection. Statistical superiority of each JTA-004 formulation over Hylan G-F 20 was however not demonstrated (p-value between 0.052 and 0.141) (Figure 1, JTA 200/2, 100/2 and 200/4 ). As the three JTA-004 formulations had a similar efficacy in terms of pain reduction, a post hoc analysis was subsequently performed between the pooled JTA-004-treated patients and the reference group. This analysis showed a 26.1 ± 2.4 (adjusted mean ± SE) mm improvement in pain in the pooled JTA-004 group vs. 15.6 ± 4.1 mm in the reference group at 6 months, demonstrating a statistically significant superiority of JTA-004 over the reference (between-group difference = -10.57; p = 0.030) (Figure 1, pooled JTA ). Figure 1. Main and post hoc analyses. All JTA-004 formulations were shown to be well tolerated and had a clinically acceptable safety profile. There was a trend for fewer treatment-related events in the JTA-100/2 group, notably no cases of post-injection mild and transient hypotension. Conclusion: This study provides a first evidence of efficacy and safety of JTA-004 in the treatment of knee OA pain. Disclosure of Interests: Marie Bettonville Employee of: Bone Therapeutics, Marc Leon: None declared, Joëlle Margaux: None declared, Didier Urbin-Choffray: None declared, Emilie Theunissen: None declared, Tatiana Besse-Hammer: None declared, Yves Fortems: None declared, Séverine Verlinden: None declared, Olivier Godeaux Consultant of: Bone Therapeutics, Anne-Sophie Delmarcelle Employee of: Bone Therapeutics, Jean-François Kaux Consultant of: Bone Therapeutics