A prospective, multi-center, randomized, double-blind feasibility study to evaluate the safety and performance of hydros joint therapy and Hydros-TA joint therapy for management of pain associated with osteoarthritis in the knee

PURPOSE:

Carbylan Osteoarthritis Research 1.0 (COR 1.0) was a prospective, multicenter, randomized, double-blind feasibility study to evaluate the safety and performance of Hydros Joint Therapy (Hydros) and Hydros-TA Joint Therapy (Hydros-TA) in subjects with Kellgren&Lawrence grade 2 and 3 osteoarthritis (OA) of the knee.

METHODS:

A total of 98 subjects were enrolled, treated, and followed for six months post-treatment. Subjects were randomized 1:1:1 to Hydros (PEG cross linked HA without TA), Hydros-TA (PEG cross linked HA with TA), or Synvisc-One Hylan G-F 20 (Synvisc-One). Hydros is a bioresorbable hyaluronan-based hydrogel suspended in a hyaluronan solution. Hydros-TA incorporates a low dose (10mg) corticosteroid, triamcinolone acetonide, suspended within the hyaluronan hydrogel, and is designed to retain steroid locally in the joint. All randomized subjects received one 6 mL intra-articular (IA) injection in the treatment knee by an unblinded injecting physician. The treatment knee was the knee that met the inclusion criteria on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A (pain) subscale score (50-90mm on 100mm VAS). Subjects and evaluating physicians who followed subjects post-treatment were blinded to treatment. Subjects were seen by a treatment-blinded evaluating physician for post-treatment follow-up at 2 weeks, 6 weeks, 13 weeks, and 26 weeks. Subjective symptom rating and physical assessment including the full WOMAC questionnaire were obtained at screening and each follow-up visit. Subject global assessment was obtained at 13 weeks and subject and physician global assessments were obtained at 26 weeks. Adverse events were solicited at all visits. The primary efficacy endpoint was the time-weighted change from baseline in the WOMAC A (pain) subscale average score for the treatment knee over 26 weeks. Differences between treatment were assessed using an analysis of covariance (ANCOVA) model.

RESULTS:

For the primary outcome, Hydros demonstrated a 41.2mm reduction, Hydros-TA demonstrated a 42.2mm reduction and Synvisc-One demonstrated a 37.5mm reduction from baseline pain. These results represented an improvement of 3.7mm and 4.7mm over Synvisc-One for Hydros and Hydros-TA respectively. Greater reductions in pain for Hydros-TA vs Synvisc-One were observed at all timepoints over the course of the study. The percentage of subjects who responded favorably to the product (as measured by the OMERACT-OARSI responder rate) was also higher in the Hydros and Hydros-TA groups when compared to Synvisc-One. Hydros-TA showed a trend towards a faster onset of pain relief compared to the non-steroid containing products evaluated in the study. Hydros-TA provided a 43.5mm mean reduction from baseline pain at the 2 week time point compared to a mean reduction of 37.7mm and 32.3mm for Synvisc-One and Hydros, respectively. In the Hydros-TA treatment group there were 3 reports of product related adverse events compared to 9 reports in the Synvisc-One group and 7 events reported in the Hydros group. Arthralgia was the most commonly reported product-related adverse event (5 reports with Synvisc-One, 4 with Hydros, and 1 with Hydros-TA).

CONCLUSIONS:

A single injection of Hydros or Hydros-TA was well tolerated and relieved pain associated with symptomatic OA of the knee over 26 weeks. The study endpoints showed strong trends toward an enhanced effect compared to Synvisc-One. In fact, in patients with OA Grade 3, the improvement in pain scores at 2 weeks was significantly greater in the Hydros-TA group compared with the Synvisc-One group. Future clinical evaluations will be required to further demonstrate the safety and the superiority of Hydros and Hydros-TA compared to Synvisc-One.