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

Study Overview
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Brief Summary
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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.

Detailed Description
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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: Analyses of tissue repair will be carried out based on the degree of lesion filling and quality of repair tissue using MRI 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. 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)

Official Title
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Follow-up Study Evaluating The Long-Term Safety and Efficacy of BST-CarGel® and Microfracture In Repair of Focal Articular Cartilage Lesions on The Femoral Condyle (Extension Study of Protocols CG-CIP01-P & CG-CIP02-P)

Conditions
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Knee Injuries

Intervention / Treatment
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* Device: Microfracture with BST-CarGel
* Device: Microfracture without BST-CarGel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject was treated under Protocol CG-CIP01 or CG-CIP02 and completed 12 month follow-up period The subject has understood and signed a Research Ethics Board(REB) approved Informed Consent Form (ICF) Exclusion Criteria: The subject was not treated under Protocol CG-CIP01-P or CG-CIP02-P The subject did not complete 12 month follow-up period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental<br>Microfracture with BST-CarGel | Device: Microfracture with BST-CarGel<br> <br> |
| Control<br>Microfracture without BST-CarGel | Device: Microfracture without BST-CarGel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of Lesion Filling (%Fill) by Repair Tissue at Degree of Lesion Filling (%Fill) by Repair Tissue at 5 Years Through MRI. | Degree of lesion filling (repair tissue volume) as measured by quantitative MRI at 5 Years post-treatment compared to the debrided lesion 1-month post-treatment (baseline). | 5 years | 
| Repair Tissue Quality (T2 MRI) | Tissue quality of the repair tissue as measured by T2 MRI as an index for collagen-based structure. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline for Knee-related Pain, Stiffness and Function at 5 Years (WOMAC Parts A, B, C) | The three sub-scales: 1) Pain, 2.) stiffness and 3.) function scores ranged from 0-10. Pain had 5 items and stiffness had 2 items, and function had 17 items. The total score for pain ranged from 0 no pain to 50 worst pain. The total score for stiffness ranged from 0 no stiffness to 20 worst stiffness. The total score for function raged from 0 no function to 170 worst function. A higher score indicates a better health state improvement. | 5 years | 
| The Number of Participants With Adverse Events Until 5 Years | Safety was assessed by recording the number of participants with Adverse Events (AEs) and their severity from the time of ICF signing up to 5 years post-treatment. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cartilage repair, Cartilage, Knee, Knee Pain, Microfracture, Arthroscopy, Bone Marrow Stimulation, Chondrogenesis, Scaffold, Chitosan, Articular Cartilage Repair