MaioRegen Prime Study for the Treatment of Deep Osteochondral Lesion of the Knee

Official title

Multicenter Prospective Randomized Study of MaioRegenTM Prime vs. Debridement (Surgical Standard of Care (SSOC)) for the Treatment of Osteochondral Lesion of the Knee Joint - OSTEOCONFIRM Study

Overview

The present study aims to compare the efficacy and the safety of MaioRegen Prime to Debridement (SSOC) in patients with deep osteochondral lesions of the knee joint. The foreseen population involves patients with osteochondral lesions with different etiology, dimension, shape, and location. The evaluation will be performed through clinical, subjective and objective assessments.

Detailed description

This is multicenter, prospective, randomized clinical trial, subjects will be randomized (2:1) to MaioRegen Prime or debridement.

All randomized patients will be followed with post-operative visits at 15 days, 6 weeks, 3, 6, 12, 18 and 24 months after surgery and annually post-24 months visit (until last patient reaches 24 months).

During screening period and at follow-up visits commonly used specific scores will be evaluated: IKDC Subjective Knee Evaluation Form, IKDC Knee Examination Form, KOOS, Tegner Score, VAS pain, PROMIS-29, ICRS Cartilage Repair Assessment and MRI related scores.

Interventions

• Device osteochondral scaffold implant
  three layered biomimetic osteochondral scaffold implant for osteochondral lesions of the knee
• Procedure SSOC
  Debridement

Primary outcome measures

• Superiority of MaioRegen Prime vs Debridement [Time frame: baseline, 24 months]

Secondary outcome measures (10)

• International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score at 24 months of MaioRegen Prime compared to debridement [Time frame: baseline, 24 months]
• Rate of responder in IKDC Subjective Knee Evaluation at 24 months of MaioRegen Prime compared to debridement as defined as improvement in IKDC Subjective Knee Evaluation of ≥15 points [Time frame: baseline, 24 months]
• Proportion of patients without SAEs related to MaioRegen treatment or debridement treatment during the 24-month follow-up period [Time frame: baseline, 24 months]
• Proportion of patients without related re-intervention after MaioRegen treatment or debridement treatment at 24 month follow-up period [Time frame: baseline, 24 months]
• Change from baseline in average overall KOOS score (Knee Injury and Osteoarthritis Outcome Score) [Time frame: baseline, 12, 18, and 24 months]
• Change from pre-injury and from baseline in Tegner score [Time frame: baseline, 12 months, 18 months, 24 months]
• Change from baseline in IKDC (International Knee Documentation Committee) Knee Examination Objective Form [Time frame: baseline, 12 months, 18 months, 24 months]
• Change from baseline in VAS (visual analogue scale) pain [Time frame: baseline, 12 months, 18 months, 24 months]
• PROMIS-29 (Patient-Reported Outcomes Measurement Information System): Patient's QOL (quality of life) improvement [Time frame: baseline, 12 months, 18 months and 24 months]
• MRI evaluation: MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) 2.0 Knee Score [Time frame: baseline, 12 months, 24 months]

Eligibility criteria

Inclusion criteria

• Informed consent prior to any study-related procedures;
• Male or female patients aged between 18 and 60 years (inclusive);
• Body Mass Index (BMI) ≤ 35;
• Up to 3 treatable osteochondral lesions localized in femoral condyles and/or trochlea (the patient might have other lesion in other parts of the joint, but they should not be more severe than ICRS Grade II lesions as determined by baseline MRI);
• Knee osteochondral lesion(s) (Grade IVa and IVb according to ICRS Classification) or not re-fixable knee Osteochondritis Dissecans lesions as determined by baseline MRI;
• Lesions with an overall treatable area 1-7 cm2 (as determined by baseline MRI). In case of multiple lesions (maximum 3 lesions) in the same knee compartment a minimum distance of 3 mm is required);
• IKDC Subjective score at baseline (pre-op evaluation) is less than 70;
• Non-responsive to physical therapy for at least 6 weeks;
• Patients physically and mentally willing and able to comply with the post-operative rehabilitation protocol and scheduled clinical and radiographic visits.

Exclusion criteria

• IKDC subjective score at Baseline is more than or equal to 70;
• KOOS Pain Subscale score at baseline is less than 20 or more than 65 (scale: maximum pain = 0, pain free = 100);
• Osteochondral tibial plateau and/or patella defects;
• Patients affected by advanced osteoarthritis in the index knee (Kellgren and Lawrence classification 3 or 4);
• Bony defect depth deeper than 5 mm, according to baseline MRI, measured from the original subchondral bone plate level;
• Uncontained defects: lack of vital bone wall at least 2 mm thick, completely surrounding the lesion - based on MRI;
• Patients with untreated patellofemoral malalignment or who have undergone realignment procedures within 6 months;
• Patients with bone fracture or uncorrected malalignment more than 5 degrees varus or valgus according to standing X-ray.
• Patients previously treated for total or partial meniscectomy in the specific index knee compartments (more than 50% of the meniscus in the index compartments is missing);
• Patient requiring total or partial meniscectomy to be performed concomitantly, involving more than 50% of one or both menisci in the index knee compartment (lack of functional remaining meniscus, at least 5mm rim at the end of the procedure); and patient requiring ligamentoplasty and high tibial osteotomy (HTO) to be performed concomitantly;
• Untreated knee ligament instability or treated within 6 months;
• Kissing (counterposed) osteochondral lesions;
• Significant instability of the index knee according to IKDC Knee Examination Form 2000: Grade C (abnormal) or D (severely abnormal).
• Patients affected by any concomitant painful or disabling disease of the spine, hips, or lower limbs, including the contralateral knee, that would interfere with the evaluation of the index knee;
• Patients affected by bilateral knee lesions that need treatment;
• Intra-articular steroid injections within 3 months;
• Any previous cartilage repair procedure (such as: microfracture, Osteochondral autograft transplantation system (OATS), Autologous Matrix Induced Chondrogenesis, (AMIC), Autologous Chondrocyte Implantation (ACI) with or without use of a scaffold (matrix) in the index knee within one year or debridement within 6 months;
• Patients affected by osteoporosis (established through x-ray tests, called DEXA scans, bone density, etc. Criteria for osteoporosis: T-score is < - 2.5 SD), chondrodysplasia, or osteogenesis imperfecta;
• Patients affected by known allergy to equine collagen or calcium-phosphates;
• Patients who underwent chemotherapy in the past 12 months;
• Patients with a known history of any significant systemic disease (such as but not limited to: HIV, hepatitis, HTLV, syphilis, coagulopathies, insulin dependent diabetes mellitus etc.) or affected by a significant malignancy;
• Participation in other clinical trials within 90 days prior to the study or concurrent with the study;
• Patient who is pregnant (or intends to become pregnant within one-year post-op) or breastfeeding;
• Known drugs or alcohol abuse;
• Any evidence of active infection anywhere in the body. Urinary Tract Infection (UTI) patients can be included following antibiotic treatment, and provided that two consecutive cultures are negative (taken within at least 2 weeks of each other);
• Any known history of intra-articular or osseous infection of the index knee;
• Patients affected by a known history of inflammatory arthropathy or crystal-deposition arthropathy;
• Prisoners;
• The existence of any surgical or medical condition that, in the judgement of the Investigator, might compromise patient safety or the outcome of the study;
• Any medical conditions or implants that would prevent the participant from undergoing an MRI, including but not limited to pacemakers, clips, cochlear implants, or metal shrapnel.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07332182 · ORT-24

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗