Op0305 a Single Intra-Articular Injection of Jta-004 Is Safe and Efficient for Treating Symptoms in the Most Severely Affected Knee Osteoarthritis Patients – A Post Hoc Analysis of Multicenter, Randomized, Double-Blind, Placebo-and Active-Treatment Controlled Phase Iii Koa-2 Clinical Trial

Background: Osteoarthritis (OA) currently affects more than 500 million people worldwide, and despite its high prevalence, there is no disease-modifying OA drug (DMOAD) on the market. During the last decade, many intra-articular injections have been developed expecting to not only relieve symptoms but also to modify structural changes occurring in OA. Objectives: To investigate the effects of JTA-004, an innovative intra-articular treatment for knee osteoarthritis (OA) composed of hyaluronic acid, plasmatic proteins, and clonidine, on symptoms of subgroups of patients with knee OA and to compare these effects with those of saline solution and Synvisc-one®. Methods: The clinical study was a prospective, randomized, double-blind, controlled phase III clinical trial (KOA-2) comparing the effect of a single injection of JTA-004 to single injections of either Synvisc-One® or saline solution after 3 months. Men and women, 40 years or older, diagnosed with primary knee OA and an insufficient response to analgesics and/or nonsteroidal anti-inflammatory drugs were included. The primary endpoint for efficacy evaluation of JTA-004 was the mean change from baseline of the WOMAC® VA3.1 pain score compared to saline solution. The post hoc analysis addresses different sub-populations of OA patients. Results: A total of 674 patients constituted the full analysis set of KOA-2: 335 in the JTA-004, 170 in the Synvisc-One®, and 169 in the saline solution. The mean age (SD) at enrolment was 62.4 (9.0) years, with the patients ranging in age from 40 to 92 years (median of 63 years). Overall, 286 (42.4%) of the 674 patients in the FAS were ≥ 65 years of age. The majority of the patients in the FAS were female (overall 470/674 patients 69.7%). BMI at screening ranged from 18.3 to 39.8 kg/m2; the overall mean (SD) BMI was 29.78 (4.77) kg/m2. The mean VAS pain (SD) in the target knee was overall 65.5 (13.9) mm, with the mean WOMAC pain subscale score equal to 57.75 (8.28) (range 40.2 to 79.8). Overall, 374 (55.5%) of the 674 patients in the FAS had a Kellgren-Lawrence radiographic score of Grade 3 in the target knee. JTA-004 was well tolerated in all groups: the incidence, type, and severity of adverse events were similar. While no significant difference was observed between the JTA-004 and saline solution on the primary endpoint, the post hoc analysis revealed that JTA-004 was more efficient than a saline solution but not significantly different from Synvisc-One® in relieving pain in a subgroup of patients with the most severe pain (highest quartile) (Figure 1). Further, the magnitude of JTA-004's effect on the patient's algo-functional status was more important and superior to that of Synvisc-One® in patients with the most severe knee OA and with the highest level of c-reactive protein at baseline. In the JTA-004 group, the decrease of VAS pain was significantly higher for patients with the most severe knee OA at baseline (KL >2 and VAS pain ≥ 60 mm) compared to those with the least severe (KL ≤ 2 and VAS 0.05). In the JTA-004 group, the WOMAC function score decrease was significantly greater for patients with the highest CRP values (Q4) at baseline than those with the lowest CRP values (Q1)(-27.3 ± 19.8 vs -20.5 ± 22.8, p=0.043), while no differences were observed for patients included in the saline solution or Synvisc-One® groups. The same evolution was observed for WOMAC stiffness in the JTA-004 group (-26.3 ± 21.3 vs -18.7 ± 25.8, p=0.045), but not in the saline solution or Synvisc-One® group. Conclusion: A single intra-articular injection of JTA-004 is safe and efficient for treating symptoms of the most severely affected knee OA patients or with high levels of systemic inflammation, which represent a frequent endotype of synovial-driven OA. JTA-004 needs to be re-tested with a focus on patients with inflammatory and painful knee OA. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Yves Henrotin Artialis SA, Nestlé SA, Wobenzym, Allegro, Expanscience, Tilman, Grunenthal, LABRHA, Kiomed pharma., Melanie Uebelhoer Artialis SA, Asger R. Bihlet NCBD, Anne-Françoise Donneau: None declared, Justine Monseur: None declared, Edith Lau: None declared, Kirsten Müller Bested Sanos Clinic, Helene Rovsing Sanos Clinic, Francois Rieger BioSenic, Carole Nicco Biosenic.