A Study of MACI in Patients Aged 17 to 65 Years With Symptomatic Chondral or Osteochondral Defects of the Ankle

Inclusion criteria

• Age 17 to 65 at the time of planned randomization visit (Visit 2).
• One or more symptomatic chondral or osteochondral lesion/s as defined by FAOS Pain score ≤ 50 and FAOS Function (SRA) score ≤ 50.
• International Cartilage Repair Society (ICRS) Score Grade 3 or 4 chondral or osteochondral lesion/s located on the talus with or without cysts, including shoulder lesions (lesions on the talar neck), and amenable to treatment with the surgical procedure specified at randomization.
• At least 1 lesion ≥ 1.2 cm².
• Written informed consent and assent (as applicable) per Institutional Review Board (IRB) requirements.
• Participant will refrain from using Non-steroidal Anti-inflammatory Drugs (NSAIDS) for 12 weeks post-study treatment. (Post-surgical use of low-dose aspirin for clot prevention is acceptable).
• Participant will restrict pain medication to over-the-counter analgesics (NSAIDs or acetaminophen/paracetamol) after 12 weeks post-study treatment.
• Participant must have Hematocrit ≥30.0%; White Blood Cell count ≤14,000 cells/μL; Platelet Count ≥50,000 platelets/μL; Creatinine ≤2.0 mg/dL; and International Normalized Ratio (INR) ≤1.6.

Exclusion criteria

• Lesions with an underlying bony defect depth of \> 5 mm.
• Any surgery on the target joint within 24 weeks prior to Visit 1 (not including diagnostic ankle arthroscopy).
• Previous investigational drug, biologic or device use within 12 weeks prior to Visit.
• Avascular necrosis of the target ankle.
• Symptomatic musculoskeletal conditions in the lower limbs that could impede measurement of efficacy for the target ankle joint.
• Participant with "kissing lesions" (bipolar lesions, involving both the tibia and talus), or with bilateral lesions in both ankles.
• Participant with lesions that require an osteotomy procedure to allow for MACI implantation as determined at the time of ankle arthroscopy (Visit 2).
• Concomitant systemic inflammatory diseases or other conditions that affect the joints (e.g., rheumatoid arthritis, metabolic bone disease, psoriasis, symptomatic chondrocalcinosis).
• History of advanced or severe osteoarthritis of the ankle as determined by prior surgical history confirming no joint space (i.e., "bone on bone") or radiographic evidence of Modified Kellgren-Lawrence Grade 4 arthritis (i.e., osteophytes on lateral and medial malleoli and at the tibiotalar joint margins, narrowing of the joint space width \> 50%, and tibiotalar sclerosis), Van Dijk Grade III (i.e., total or subtotal destruction of the joint space) or the equivalent.
• Known history of septic arthritis in the target ankle joint within 1 year prior to Visit 1.
• Current malignancy or treatment for malignancy within the past 5 years prior to Visit 1, excluding non-melanoma skin cancer.
• Known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin.
• Females who are pregnant or lactating.
• Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems that warrant exclusion. Examples of significant problems included but are not limited to:
• Any condition that has potential for negatively impacting intra- or postoperative course (e.g., uncontrolled diabetes, heavy smoking). - Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥8.0% and/or fasting plasma glucose \>250 mg/dL (13.9 mmol/L) within the last 90 days prior to Screening Visit 1 - Heavy smoking is defined as current smoker with use of ≥20 cigarettes per day (≥1 pack/day) at the time of Screening Visit 1.
• Conditions that limit compliance with rehabilitation program.
• Any condition that has potential for significantly limiting participant's ability to assess postoperative ankle function.
• Any condition, psychiatric or otherwise, that would preclude informed consent/assent, consistent follow-up, or compliance with any aspect of the clinical trial.
• Participant is currently abusing drugs or alcohol or, in the opinion of the Investigator, at high risk for poor compliance.
• Any abnormal screening blood work that the Investigator deems clinically significant in addition to the parameters delineated in Inclusion Criterion #8.
• Injection of hyaluronic acid (HA), platelet-rich plasma (PRP), and/or corticosteroids in the target ankle within 90 days prior to Visit 1.