Safety and Effectiveness Study to Evaluate NOVOCART® 3D Plus Compared to the Microfracture to Treat Articular Cartilage Defects of the Knee (N3D)

Inclusion Criteria:

• Patient is ≥18 and ≤65 years old at time of screening.
• Patient has symptomatic knee pain indicative of articular cartilage defects of the knee unsuccessfully treated with conservative care (e.g., analgesics, rest, and physical therapy).
• Patient has an intact (<Grade 2 ICRS classification) articulating joint surface (no "kissing lesions").
• Patient has an intact meniscus (maximum 1/3-resection).
• Patient needs to have a stable knee joint or sufficiently repaired knee ligaments (Lachman-Test 1° stable endpoint, KT-1000 ≤ 2mm in side-to-side difference, Pivot-shift-test < 1° positive). If ligament repair is necessary, the repair has to be performed close by cartilage treatment (Ligament repair < 6 weeks after ACT/microfracture).
• Patient has free range of motion of the affected knee joint.
• Patient has a defect site of the medial or lateral femoral condyle or the trochlea.
• Patient has a defect size >3 and <5 cm2.
• Patient has a defect grade III or IV according to the ICRS classification.
• Patient has a maximum baseline score of 60/100 on the 2000 IKDC subjective knee evaluation.
• Patient is a male, or is a female using a reliable method of artificial birth control or has documented infertility.
• Patient is willing and able to give written informed consent to participate in the study.
• Patient is willing and able to comply with all study requirements, including attending all follow-up visits and assessments and postoperative rehabilitation regimen.

Preoperative Exclusion Criteria:

• Patient is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.
• Patient is unable to undergo magnetic resonance imaging (MRI).
• Patient has prior surgical treatment of the target knee using mosaicplasty and/or microfracture (Note: prior debridement and lavage are acceptable). Anterior cruciate ligament repair has not to be excluded, if the target knee is stable or a primary ACL reconstruction is performed within 6 weeks after cartilage treatment.
• Patient has radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade >2.
• Patient has osteoarthritis, rheumatoid arthritis, metabolic (gout and pseudo-gout) and/or infectious arthritis.
• Patient does not accomplish a joint extension of 0° and/or a joint flexion of 130° (neutral 0 method) with the target knee.
• Patient has joint space narrowing >1/3 in the target knee when compared to the other knee or <3 mm joint space measured on x-ray.
• Patient has a meniscus deficiency ≥1/3 of the meniscus in the target knee.
• Patient has had surgery on the contralateral knee within 8 weeks prior to the scheduled arthroscopy. (Note diagnostic arthroscopies and reconstruction of the anterior cruciate ligament for reestablishment of ligament stability in the target knee is acceptable).
• Patient has instability of the anterior (Lachman-Test >1°, KT-1000 > 2mm in side-to-side difference, Pivot-shift-test ≥ 1° positive) or posterior cruciate ligament (> 2mm side to side in posterior stress view), posterior lateral or lateral collateral corner (≥ 2°), chronic instabilities of the medial collateral ligament (Grade II-III, > 3 months after trauma) in the target knee.

In case of instability to the anterior cruciate ligament and/or fresh medial collateral ligament (<3 months after trauma), inclusion into the study is possible if instability has been sufficiently therapied through substitute ACL surgery and/or medial collateral refixation within 6 weeks after scheduled cartilage transplantation/microfracture. Patients with revision ACL repairs have to be excluded.

• Patient has arthrofibrosis resulting in >50% reduced patellar mobility in the target knee.
• Patient has had prior release and excision of scar tissue except isolated lateral release in the target knee.
• Patient has malalignment (no valgus- or varus-deformity) in the target knee. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in a.p. or rather p.a. projection. The Mikulicz line is not allowed to deviate more than 5 mm of the Eminentia intercondylaris.
• Patient suffers from femoropatellar pain syndrome, not exclusively explained by the cartilage defect(s) of the trochlea femoris. Patient has had a patellar dislocation.
• Patient has patella dysplasia > Wiberg III.
• Patient has trochlea dysplasia with an angular aperture ≥ 150° according to Brattström.
• Patient has a TTTG distance ≥ 20 mm.
• Patient has a M. Osgood-Schlatter and/or a M. Sinding-Larssen-Johansson.
• Patient has osteochondritis dissecans necessitating bone grafting or previous bone graft repair of defect site.
• Patient has bilateral lower limb pain or low back pain.
• Patient has a bone disease, including Paget's disease.
• Patient has a connective tissue or collagen disease including but not limited to Ehlers-Danlos disease.
• Patient has diffuse chondromalacia with disseminated damage (degree Ia to II according to ICRS classification), also outside the loading zone, evidenced by arthroscopy.
• Patient has diabetes with an HbA1c >7% less than 30 days before the arthroscopy.
• Patient has an autoimmune disease.
• Patient has an immunological suppressive disorder or is taking immunosuppressants.
• Patient is currently taking steroids and/or has used steroids within the last 3 months prior to screening.
• The patient has a known history of HIV/AIDS.
• The patient has a known history of Treponema pallidum (syphilis).
• The patient has an active hepatitis B or C infection with verified antigens. Patients with a cured hepatitis B or C infection and/or verified antibodies are not excluded.
• The patient has an active systemic or local microbial infection, eczematization or inflammable skin alterations at the site of surgery (including Protozoonosis: Babesiosis, Trypanosomiasis (e.g. Chagas-Disease), Leishmaniasis, persistent bacterial infections, like Brucellosis, spotted and typhus fever, other Rickettsiosis, Leprosy, Recurrent Fever, Melioidosis or Tularaemia).
• Patient has had cancer in the bones, cartilage, fat or muscle of the treated limb or any other cancer except non-melanoma skin cancer within the past 5 years.
• Patient has a vascular disorder including but not limited to peripheral vascular disease.
• Patient is taking indomethacin (known to have catabolic effects on chondrocytes), anticoagulant or antiplatelet medications such as salicylates (e.g., Aspirin®). Note: the use of indomethacin, anticoagulant or antiplatelet medications must be discontinued at least 3 weeks prior to surgery. Temporary medication with heparins for postoperative thrombosis prevention is acceptable.
• Patient is considered to be at high risk for osteoporosis or osteopenia including patients who are postmenopausal, amenorrheic for more than one year, have a history of maternal hip fracture, have primary hyperparathyroidism or hyperthyroidism, have chronic renal failure or have had previous fragility fractures unless there is a documented DXA T-score of > -1 in bone density measurement within the past 3 months; also patients with primary hyperparathyroidism, hyperthyroidism, chronic renal failure or patients with prior pathological fractures independent of the genesis.
• Patient has any degenerative muscular or neurological condition that would interfere with evaluation of outcome measures including but not limited to Parkinson's disease, amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS).
• Patient has a body mass index (BMI) >30 kg/m2.
• Patient is a woman who is pregnant, lactating or anticipates becoming pregnant within 24 months after surgery.
• Patient is currently participating, or has participated in any other clinical study within 3 months prior to the screening visit.
• Patient has known current or recent history of illicit drug or alcohol abuse or dependence defined as the continued use of alcohol or drugs despite the development of social, legal or health problems.
• Patient has psychiatric or cognitive impairment that, in the opinion of the investigator, would interfere with the patient's ability to comply with the study requirements, e.g., Alzheimer's disease.
• Patient has any other condition, which, in the opinion of the investigator, would make the patient unsuitable for the study.

Intraoperative Exclusion Criteria:

• Patient has a defect size <3 or >5 cm2.
• Patient has >1 independent cartilage lesion in one knee that need to be treated with NOVOCART® 3D plus or microfracture.
• Patient is indicated for concurrent realignment or meniscus transplant.
• Patient has bone loss or deep defects that require bone grafting.