HyaloFAST Trial for Repair of Articular Cartilage in the Knee

Defect of Articular Cartilage Clinical Trial

— FastTRACK  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02659215
• Other study ID #: Hyalofast 15-01
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 2015
• Est. completion date: June 30, 2026

Study information

• Verified date: June 2023
• Source: Anika Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

• 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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Cartilage Diseases
• Defect of Articular Cartilage

Intervention

Device:
• Hyalofast
Implantation of Hyalofast scaffold with autologous bone marrow aspirate concentrate via arthroscopy/mini-arthrotomy.

Procedure:
• Microfracture
Microfracture is a well-established arthroscopic surgical technique for cartilage repair which involves several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect, with resultant complete defect fill by a well-anchored clot

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz
Austria	Universtitatsklinkik Krems	Krems
Austria	Kepler University Clinic	Linz	Upper Austria
Austria	Krankenhaus der Barmherzigen Schwestern	Ried	Upper Austria
Austria	University Hospital Tulln	Tulln	Lower Austria
Austria	Evangelisches Krankenhaus	Vienna
Austria	Medical University of Vienna	Vienna
Austria	Private Hospital Doebling	Vienna
Estonia	North Estonia Medical Center	Tallin
Estonia	Ortopeedia Arstid AS	Tallinn
Hungary	Health Center of Downtown-Lipotvaros, Orthopedic Outpatient Clinic (Belvárosi-Lipótvárosi Egészségügyi Szolgálat Ortopeadia)	Budapest
Hungary	Jutrix Medical Llc	Budapest
Hungary	Magyar Honvedseg, Egeszseugyi Kozpont, Balesteti Sebeszeti Osztaly	Budapest
Hungary	Menta Egeszsegkozpont Kft.	Budapest
Hungary	Semmelweis Egyetem Orthopaedic Clinic (Ortopédiai Klinika)	Budapest
Hungary	Uzsoki Hospital, Department of Traumatology	Budapest
Hungary	DE KK Ortopediai Klinika	Debrecen
Hungary	Somogy Megyei Kaposi Mór Oktatókórház	Kaposvár
Hungary	Kastelypark Klinka	Tata
Indonesia	Medistra Hospital	Jakarta
Indonesia	Royal Progess Hospital	Jakarta
Italy	Instituto Ortopedico Rizzoli	Bologna
Italy	A.O. Universitaria San Martino Monoblocco	Genova
Italy	University Federico II	Naples
Lithuania	AB "Ortopedijos technika"	Kaunas
Lithuania	Vilnius University Hospital Santaros klinikos	Vilnius
Mexico	Desarrollo Ético en Investigación Clínica S.C.	Guadalajara
Mexico	Cruz Roja Mexicana (Hospital de Ortopedia de la Cruz Roja Mexicana)	Mérida
Mexico	Hospital Universitario Dr. José Eleuterio González	Monterrey
Philippines	De La Salle Medical and Health Sciences Institute	Cavite
United States	Austin Ortho Biologics / Seton Medical Center Austin	Austin	Texas
United States	Bone and Joint Clinic of Baton Rouge	Baton Rouge	Louisiana
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Covington Orthopedic and Sports Medicine Institute	Covington	Louisiana
United States	Clinical Research Center of Nevada	Las Vegas	Nevada
United States	Axis Clinical Trials	Los Angeles	California
United States	Kerlan-Jobe Orthopedic Clinic	Los Angeles	California
United States	Paramount Trials, LLC	Miami	Florida
United States	Epic Medical Research	Murray	Utah
United States	Suncoast Clinical Research	New Port Richey	Florida
United States	New York Presbyterian Hospital	New York	New York
United States	Penn Medicine	Philadelphia	Pennsylvania
United States	OrthoIllinois	Rockford	Illinois
United States	BioSolutions Clinical Research Center	San Diego	California
United States	Orthopedic Foundation	Stamford	Connecticut
United States	New Hope Research Development	Tarzana	California
United States	Physicians Research Group	Tempe	Arizona
United States	Baylor Scott & White	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Anika Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Estonia,  Hungary,  Indonesia,  Italy,  Lithuania,  Mexico,  Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Superiority of Hyalofast with Bone Marrow Aspirate Concentrate (BMAC) vs. Microfracture for % Change in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain Score	Co-primary endpoint	2 years post-surgery
Primary	Superiority of Hyalofast with Bone Marrow Aspirate Concentrate (BMAC) vs. Microfracture for % Change in International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score	Co-Primary Endpoint	2 years post-surgery
Secondary	Superiority of Hyalofast® with autologous BMAC vs. Microfracture for change in MRI MOCART Score from baseline to two years post-surgery		2 years post-surgery
Secondary	Superiority of Hyalofast® with autologous BMAC vs. Microfracture for change in Evaluator Global Assessment from baseline to two years post-surgery		2 years post-surgery
Secondary	Superiority of Hyalofast® with autologous BMAC vs. Microfracture in change in individual KOOS subscales from baseline to two years post-surgery		2 years post-surgery
Secondary	Superiority of Hyalofast® with autologous BMAC vs. Microfracture in change in IKDC Knee Examination Form domains from baseline to two years post-surgery		2 years post-surgery
Secondary	The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE), will be collected for all participants.		3 years post-surgery