Neocartilage Implant to Treat Cartilage Lesions of the Knee

Study Overview
=================
Brief Summary
-----------------
ISTO Technologies, Inc. is proposing a clinical study with 225 subjects, to establish the safety and efficacy of the Neocartilage Implant for the treatment of ICRS Grade 3 and 4 articular cartilage lesions of the knee compared to microfracture treatment.

Detailed Description
-----------------
In the United States alone, more than 500,000 cartilage lesions per year require some treatment to reduce pain, restore joint mobility, and prevent further damage caused by the progression of osteoarthritis. The lack of effective cartilage repair approaches or products for restoration of defective articular cartilage to its native, hyaline morphology only continues to exacerbate the incidence of osteoarthritis as these initial defects enlarge and degrade over a 10 to 20 year period. The repair of cartilage, especially in the knee, remains a formidable clinical challenge. Regenerative medicine approaches to cartilage repair have only begun to be explored as possible options and there is a clear trend toward biological solutions for the repair and regeneration of damaged or diseased articular cartilage. The study was designed to compare how well the Neocartilage Implant works against the microfracture therapy, a widely used and accepted cartilage repair therapy. Data to be collected include Pain and Function in Daily Living scores, symptoms, Function in Sports and Recreation, and Knee Related Quality of Life. Additionally, MRI and X-rays will be collected to evaluate the cartilage repair progress. These assessments will be used through the five years of post-operative follow-up.

Official Title
-----------------
Randomized Controlled Trial to Evaluate the Efficacy of a Neocartilage Implant in the Management of ICRS Grade 3 to 4 Articular Cartilage Lesions of the Knee

Conditions
-----------------
Articular Cartilage Disorder, Degeneration; Articular Cartilage, Chronic Cartilage Injury, Acute Cartilage Injury, Defect of Articular Cartilage

Intervention / Treatment
-----------------
* Biological: Neocartilage Implant/DeNovo® ET (Engineered Tissue Graft)
* Other: Microfracture


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Generally, the following inclusion criteria must be met, however, this is not a complete list. Male or Female between the ages of 18 and 60 (1) or (2) articular cartilage lesions of the distal femur ranging in no more than 5 cm2 each Ipsilateral knee compartment has intact menisci (or meniscectomized remnant with > 5mm wide rim) and stable ligaments in the affected knee 3 months out from initiation of conservative non-surgical management (e.g.hyaluronic acid injection, activity modification) or previous minimal surgical intervention (e.g., arthroscopic lavage, debridement) or 12 months out from marrow stimulation for this condition Exclusion Criteria: Generally, if a potential participant meets any of the following criterions, they will not be eligible for this study. Additionally, more criteria will be evaluated to confirm eligibility as this list is not a complete list of criteria. Osteoarthritis Rheumatoid arthritis History of septic or reactive arthritis Gout or a history of gout or pseudo-gout in the affected knee Osteochondritis dissecans or osteochondral lesions of the knee with bone loss > 6mm deep Bipolar articular cartilage involvement (or kissing lesions) of the ipsilateral compartment (i.e., > than ICRS Grade 2 on the opposing articular surface) Associated damage to the underlying subchondral bone requiring an osteochondral graft Is pregnant or breast-feeding Has a BMI > 35 (kg/m2) Has prior total meniscectomy of either knee Has received, within the past three months, intra-articular hyaluronic acid therapy, or steroid therapy Has more than two clinically relevant chondral lesion(s) on the index knee

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Neocartilage Implant<br>Neocartilage Implant surgically implanted and affixed to subchondral bone using commercial fibrin during mini-open knee arthrotomy. | Biological: Neocartilage Implant/DeNovo® ET (Engineered Tissue Graft)<br>* The Neocartilage Implant is a cartilage repair technology cultured from juvenile human cartilage cells.<br>* Other names: RevaFlex;|
| Other: Microfracture<br>Standard of care cartilage repair technique. | Other: Microfracture<br>* Marrow stimulation using the microfracture technique; performed arthroscopically<br>* Other names: marrow stimulation;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee Injury and Osteoarthritis Outcomes Scores (KOOS) | Knee Injury and Osteoarthritis Outcomes Scores (KOOS) Pain and Function in Daily Living (ADL) subscales. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IKDC Knee Examination |  | Baseline, 6 week, 6, 12, 18, 24 months and annually through 5 years | 
| Subject reported questionnaires | Various questionnaires are required to be completed by the subject before and after treatment throughout the study. | Baseline, 6 week, 6, 12, 18, 24 months and annually through 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
juvenile, cartilage, knee surgery, cartilage injury, knee pain, cartilage repair, cartilage damage, cartilage lesion, cartilage defect, articular cartilage lesion, articular cartilage defect, cells, ISTO Technologies, Neocartilage, RevaFlex