Follow-Up Study Evaluating The Long Term Safety and Efficacy of BST-CarGel and Microfracture Repair of the Knee

Overview

This follow-up study will evaluate the effects of BST-CarGel® application to a microfractured lesion (investigational) and microfracture alone (control) for up to 5 years from treatment in subjects, treated under Protocols CG-CIP01-P and CG-CIP02-P, and will serve as a post approval study for these Protocols, in support of a commercial application. The lesions treated under Protocols CG-CIP01-P and CG-CIP02-P were focal lesions of articular cartilage, grade 3 or 4 (either ICRS or Outerbridge classification) on the medial and lateral femoral condyles of the knee, and were classified as either acute or chronic.

Cartilage repair currently remains a problematic orthopedic concern with no effective solution. The development of new surgical techniques or therapies is critical in meeting this medical need. Clinical data regarding the long-term durability of repair tissue resulting from cartilage repair techniques such as microfracture, autologous chondrocyte implantation or mosaicplasty is lacking. Only two studies, one comparative and one uncontrolled, have examined long-term repair outcomes (over 4 years). These studies reinforced the concept that further studies are needed to identify a technique or product that will lead to long-term clinical benefit through improved cartilage repair efficacy. BST-CarGel® is a medical device derived from chitosan applied to a microfractured lesion and has been shown to promote the quantity and quality of cartilage repair tissue in animals. The efficacy and safety of BST-CarGel® is currently being evaluated in humans as compared to the standard of care treatment, microfracture, in a 12 month international study in Canada, Europe and Korea under Protocols CG-CIP01-P and CG-CIP02-P. When these protocols were designed and carried out, the BST-CarGel® technology belonged to BioSyntech Canada Inc. Afterwards, the technology was acquired by Piramal Healthcare (Canada) Ltd. which is now the owner of the technology and the sponsor for this Extension Study CG-C1P04. This follow-up study will evaluate the long-term effects (5 yrs) of BST-CarGel® + microfracture and microfracture alone in subjects treated in the pivotal and sub-studies. All eligible subjects (maximum 80) who were treated under Protocols CG-CIP01-P and CG-CIP02-P and completed the required 12 month follow-up period will be asked to participate in this follow-up study. The stratification from Protocols CG-CIP01-P and CG-CIP02-P (investigational site and lesion type) will be retained for the purposes of the follow-up study, and all third parties such as the MRI central reading facility will remain blinded to the treatment received under Protocols CG-CIP01-P and CG-CIP02-P. Comparisons between the two treatment groups will be performed. The following assessments will be done annually at years 3 and/or 4 and 5 post -treatment under Protocols CG-CIP01-P and CG-CIP02-P in subjects treated with BST-CarGel + microfracture or microfracture alone: 1. Analyses of tissue repair will be carried out based on the degree of lesion filling and quality of repair tissue using MRI 2. The general health status of subjects will be captured in the case report form (CRF) and will include the subject's overall health status, treated knee status, adverse events (AEs) and concomitant medications. 3. The assessment of the subject's knee pain, stiffness, functional ability and quality of life through self-assessment questionnaires (Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and short-form-36 (SF-36v2)