Safety and Efficacy of hUC-MSC for the Treatment of Cartilage Damage in the Knee Joint

Phase I/IIa Study to Test the Safety and Efficacy of MSC From Umbilical Cord Tissue (UC-MSC) for the Treatment of Cartilage Damage in the Knee Joint

Testing the safety and efficacy of MSC from umbilical cord tissue (UC-MSC) for the treatment of cartilage damage in the knee joint

All patients who provide written informed consent after receiving detailed information about the study and its potential risks will undergo a screening to assess eligibility. This is a prospective, multicenter, single-arm, open-label clinical trial. On Visit 1 (Day 0), eligible patients will receive knee surgery with a one-time application of the investigational product to the cartilage defect. Follow-up visits over a two-year period will be conducted at regular intervals to monitor the safety of the investigational product and to collect initial data on its efficacy.

Inclusion Criteria:

• Patients of any gender with an age from ≥ 18 years to ≤ 60 years
• Clinical indication for a surgical cartilage regeneration procedure
• Symptomatic grade III/IV cartilage defect according to ICRS or osteochondral defect with a maximum depth of 3 mm
• A cartilage defect requiring treatment with a defect size of 2-6 cm² on the femoral condyles or patella or trochlea
• Affected and contralateral knee (if known): Kellgren-Lawrence (K/L) osteoarthritis severity < grade III
• KOOS pain sub-score of ≤ 70 (out of max. 100) in the affected knee joint and > 80 (out of max. 100) in the contralateral knee joint measured without taking analgesics within the last 24 hours
• BMI < 35 kg/m²
• Written informed consent of the participant, also regarding alternative procedures such as cartilage transplantation (MACT) or matrix-augmented bone marrow stimulation (BMS, AMIC)

Exclusion Criteria:

• Clinical indication explicitly for a cartilage regeneration procedure other than the intended study treatment

• Known varus or valgus malalignment of the affected leg of ≥ 5°

• Antero-posterior or medio-lateral instability

• Meniscus loss of more than 20% in the affected compartment

• Patella instability

• Simultaneous surgery on other joint structures (cruciate ligament replacement, meniscus suture, partial meniscus resection > 20%, osteotomy)

• Simultaneous higher-grade (ICRS grade III/IV) cartilage damage on the corresponding joint surfaces to the treated cartilage damage ("kissing lesions")

• Osteoarthritis Kellgren-Lawrence (K/L) grade III or IV

• Arthrofibrosis

• Metabolic arthropathy

• Collagenosis

• Autoimmune disease

• Tumor disease within the last 5 years

• Neuromuscular disease

• Peripheral arterial occlusive disease

• Intra-articular application of hyaluronic acid or glucocorticoids or platelet concentrates within the last 6 months

• Joint replacement in the contra-lateral knee or hip within the last 12 months

• Rheumatoid arthritis or other inflammatory diseases such as autoimmune diseases, seronegative spondyloarthritis, gout, pseudogout

• Previous fracture in the affected knee joint

• Osteoporosis

• Contraindications against the planned operation under general anesthesia

• Relevant secondary diseases that increase the risk of surgery, e.g. cardiac insufficiency, coronary heart disease, coagulation disorders, diabetes mellitus, liver cirrhosis, renal insufficiency, etc.

• History of known hypersensitivity to porcine collagens, human albumin, glucose or components of fibrin adhesives used in orthopaedics or surgery

• Simultaneous participation in another interventional clinical trial (incl. within the last 4 weeks prior to inclusion)

• Addiction or other illnesses that do not allow the person concerned to assess the nature, scope and possible consequences of the clinical trial (lack of capacity to consent)

• Indications that the patient is unlikely to adhere to the protocol (e.g. lack of compliance)

• Persons who are placed in an institution by court or official order

• Persons who are dependent on the sponsor

• Pregnant or breastfeeding women

• Women of childbearing age, except women who meet the following criteria:

  1. Post-menopausal (12 months natural amenorrhea)

  2. Post-operative (6 weeks after bilateral ovariectomy with or without hysterectomy or bilateral salpingectomy)

  3. Presence of a negative pregnancy test (urine, not older than 14 days on the day of surgery) and willingness to regularly and correctly use a contraceptive method with a Pearl Index < 1 % per year:

     3.1 Combined (oestrogen and progestogen-containing) hormonal contraception 3.2 Hormonal contraception containing progestogens (oral, injected, implanted) 3.3 IUD (hormonal IUD, copper IUD)

  4. Sexual abstinence

  5. Vasectomy of the partner