HyaloFAST Trial for Repair of Articular Cartilage in the Knee

A Prospective, Randomized, Active Treatment-controlled, Evaluator-blinded Multicenter Study to Establish the Superiority of Hyalofast® With BMAC in the Treatment of Articular Knee Cartilage Defect Lesions in Comparison to Control

The purpose of this study is to evaluate the safety and efficacy of Hyalofast® scaffold with bone marrow aspirate concentrate (BMAC) compared to microfracture in the treatment of symptomatic cartilage defects of the knee.

• Prospective, randomized, active treatment-controlled, evaluator-blinded (radiologist reviewer and physician evaluator) multicenter study (up to 40 sites in the US and EU).
• All subjects that meet preoperative screening eligibility criteria will be randomized to treatment with Hyalofast® with BMAC or Microfracture.
• Hyalofast® is a sterile, biodegradable non-woven pad (2 x 2 cm or 5 x 5 cm) that is composed of HYAFF-11®, a benzyl ester of hyaluronic acid. Hyalofast® acts as a biodegradable support for the autologous bone marrow aspirate concentrate. Hyalofast® is soft and conformable and can easily be cut to fit the lesion size.
• Autologous bone marrow is harvested from the subject intraoperatively during the Index Procedure. Approximately 60 mL of bone marrow will be aspirated from the subject's iliac crest using the SmartPrep 2 Bone Marrow Processing Pack. The cellular rich portion will be concentrated via the SmartPrep BMAC 2 Centrifuge System at point-of-care to provide 7 mL of bone marrow aspirate concentrate (BMAC). 1 - 2 mLs will be used for post-procedure testing of total nucleated cells, cell viability, and sterility.
• Hyalofast® with BMAC is implanted during either a standard knee arthroscopy or min-arthrotomy depending upon surgeon preferences and intra-operative findings. The lesion to be treated will be debrided to a stable cartilage margin. The defect will be sized and Hyalofast® will be cut to fit the lesion area. If necessary, more than one Hyalofast® pad can be overlapped to cover the lesion. 2 mL of BMAC will be loaded per Hyalofast® scaffold and then implanted to cover the defect. Hyalofast® with BMAC readily adheres to the site of application, but, if necessary, can be secured to the defect margins with an FDA-approved fibrin glue.
• All subjects will be assessed at intervals post-procedure (1 month, 3 months, 6 months, 12 months, 24 months, and 36 months).
• Subjects will be required to follow a strict pre-specified post-surgery rehabilitation protocol specific to the defect location.
• Measures to assess effectiveness will be conducted at follow-ups, with the primary effectiveness endpoint assessment done at the 24 month timepoint.
• Evaluators doing efficacy assessments of the subject and administering subject-reported outcome instruments will be blinded to the treatment.
• Safety will be assessed by the collection of adverse events at all timepoints.
• Magnetic Resonance Imaging (MRI) will be conducted at Screening, 1 month, 12 months, 24 months, and 36 months. Evaluation of the MRIs, including the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, will be done by blinded radiologist reviewers. The one month MRI will be used as the baseline MRI for evaluation of treatment effectiveness.

Inclusion Criteria:

1. Patient is male or female, between 18 and 60 years of age
2. Patient's body mass index (BMI) is <35 kg/m2
3. Patient has a symptomatic lesion of the femoral condyle (medial and/or lateral) or femoral trochlea that is between 1.5 - 6 cm2 on screening images confirmed by the independent radiologist
4. The symptomatic lesion is classified as International Cartilage Repair Society (ICRS) grade 3 or 4
5. Patient agrees to actively participate in a strict rehabilitation protocol and follow-up program
6. Patient is using only nonsteroidal anti-inflammatory drugs or acetaminophen/paracetamol during the month before signing the informed consent form to treat knee pain
7. Patient is willing and able to provide informed consent and comply with study requirements
8. Patient, if woman of childbearing potential, must have a negative pregnancy test at Screening, cannot be lactating and is willing to use adequate contraception for the first 12 months of the study after the last surgery
9. Patient has ability to consistently rate knee pain and function as demonstrated by completion of total KOOS score
10. Patient has a minimum of 45 out of 100 Visual Analogue Scale (VAS) score for index knee pain when remembering index knee pain when not on medication and when active
11. Patient is willing to use other pain medication rather than Non-steroidal Anti-inflammatory Drugs (NSAIDS) for 6 months post-surgery (e.g. acetaminophen, or narcotic analgesics, if prescribed). Post-surgical use of aspirin for clot prevention is acceptable.
12. Patient is willing to restrict pain medication after 6 months post-surgery to NSAIDs or acetaminophen/paracetamol only through the end of the trial
13. Patient must have Hematocrit ≥ 28.0%; White Blood Cell count ≤ 14,000; Platelet Count ≥ 50,000; Creatinine ≤ 2.0 mg/dL; and International Normalized Ratio (INR) ≤ 1.6

Exclusion Criteria:

1. Major concomitant cartilage lesions which require extensive surgical treatment. (Lesions such as minor loose bodies, small debris fragments, small cartilage fragments or prominent knee fat pad are allowed. These lesions may be treated with debridement).
2. Presence of a kissing bipolar lesion that is apposed to the index lesion and is deeper than Grade 2 (ICRS classification) as determined by MRI. (Presence of a kissing (bipolar) lesion that is apposed to the index lesion and is deeper than Grade 2 and is discovered under arthroscopy are allowed). The non-index lesion, if indicated for treatment, should be treated with the study assigned treatment of the index lesion.
3. Diagnosed advanced osteoarthritis as demonstrated by a Kellgren-Lawrence grade of 3 or 4 in the index knee
4. Complex ligamentous instability of the index or contralateral knee. (Previous reconstructions of Anterior Cruciate Ligament (ACL) or Posterior Cruciate Ligament (PCL) are allowed, of either the index or contralateral knee, if instability is not present. Grade 1 ligamentous injury are allowed)
5. Infections or skin diseases at target knee joint
6. Osteochondritis dissecans (OCD)
7. Patients requiring meniscal arrow or meniscal sutures
8. Previous meniscal transplant in the index knee
9. Patients with previous total or functional meniscectomy. (Patients with a previous partial meniscectomy and a meniscus that is considered biomechanically functional are allowed)
10. Varus or valgus malalignment exceeding 10° in either knee
11. Patient requiring concomitant surgical procedures at the time of Index Procedure such as osteotomies (e.g. high tibial valgus and/or patellar realignment osteotomy), bone subchondral perforation, ligament surgery, meniscal surgeries etc.
12. Previous cartilage repair procedure (microfracture, Osteochondral autograft transplantation system (OATS) or Autologous Chondrocyte Implantation (ACI) with or without use of a scaffold (matrix) in the index knee
13. Previous failed microfracture procedure in index knee. (Previous history of microfracture in the contralateral knee is allowed)
14. Known hypersensitivity (allergy) to hyaluronate
15. Contraindication(s) to microfracture surgery
16. Hyaluronic acid intra-articular injections into the index knee within the last 90 days before signing informed consent
17. Corticosteroid therapy by systemic or intra-articular route within the last 60 days before informed consent or intramuscular or oral corticosteroids within the last 30 days before informed consent.
18. Uncontrolled diabetes
19. Any concomitant painful or disabling disease of the spine, hips, or lower limbs, including the contralateral knee, that would interfere with evaluation of the index knee
20. Any clinically significant or symptomatic vascular or neurologic disorder of the lower extremities
21. Any evidence of the following diseases in the index knee: septic arthritis; inflammatory joint disease; gout; recurrent episodes of pseudogout; Paget disease of bone; ochronosis; acromegaly; hemochromatosis; Wilson disease; primary osteochondromatosis; heritable disorders; collagen gene mutations
22. Rheumatoid arthritis or gouty arthritis
23. Current diagnosis of osteomyelitis
24. Any result from screening blood work (including complete blood count, Prothrombin Time (PT)/Partial Thromboplastin Time (PTT)/INR, liver function, and creatinine) that exceeds 1.5x the upper limit of normal or is below 0.5x the lower limit of normal.
25. Diagnosed musculoskeletal cancer or any diagnosed cancer, other than musculoskeletal if not on long term remission (e.g. at least 5 years or negative biopsy at last exam), except basal cell carcinoma
26. Alcohol and drug (including medication) abuse
27. Patients who are at higher risk for post-surgical bleeding (e.g., bleeding disorder; taking anticoagulants except low dose aspirin) or post-surgical infection (e.g., taking immunosuppressants; have a severe infection or a history of serious infection)
28. Contraindications to MR imaging
29. Patient is currently receiving workman's compensation or disability or is in litigation for workman's compensation or disability claims
30. Participation in concurrent trials or in previous trial within 90 days of signing informed consent