Comparison of BioCart™II With Microfracture for Treatment of Cartilage Defects of the Femoral Condyle

Symptomatic Cartilage Defects of the Femoral Condyle Clinical Trial

Official title:

Phase II Study to Investigate the Efficacy and Safety of BioCart™II in the Treatment of Symptomatic Cartilage Defects of the Femoral Condyle in Comparison With Microfracture

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00729716
• Other study ID #: BioCart™II 005-06
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 4, 2008
• Last updated: April 16, 2012
• Start date: May 2008
• Est. completion date: May 2015

Study information

• Verified date: March 2012
• Source: ProChon Biotech Ltd
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIsrael: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

BioCart™II is a novel scaffold seeded with autologous chondrocytes to be used to repair cartilage lesions of the knee. This study is designed to compare the efficacy and safety of BioCart™II treatment compared to microfracture which is the classical method of treatment.

Description:

Full thickness cartilage lesions are typically incapable of self repair, are a source of pain and morbidity and lead to early onset osteoarthritis. A classical method of treatment has been microfracture where holes are drilled in the subchondral bone to allow influx of bone marrow cells which fill and repair the lesion. The resulting repair has been reported to be mixed fibrocartilage which is recognized to be less efficient and durable than hyaline cartilage, the physiological material making up the joint. In autologous chondrocyte implantation, a sample of cartilage is removed from a non-weight bearing region of the joint and the cells are grown and expanded in culture and then returned to the knee to repair the damaged cartilage. For implantation with BioCart™II, the chondrocytes are grown in the presence of proprietary growth factors which maintain the chondrocytes in optimal condition for subsequent repair. For implantation, the cells are seeded on a completely human three dimensional spongelike scaffold which holds the cells in the correct topology to allow for a rapid repair of the damaged joint with true physiological cartilage. BioCart™II is user friendly for the surgeon and patient alike giving it an advantage over other methods for autologous chondrocyte implantation that are in clinical use.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: May 2015
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 60 Years

Eligibility

Inclusion Criteria:

• Age 16 to 60 years

• Femoral condyle lesion (medial, lateral or trochlea)

• Single contained lesion

• Symptomatic (moderate to severe pain on VAS)

• Caused by trauma or OCD

• Depth of lesion up to 6 mm

• Size of lesion 1.5-7.5 cm2

• No general bone or cartilage pathology

• No limb mal-alignment (long leg standing X-ray)

• Mechanically stable knee

• Accompanying pathology menisectomy up to 50%

• Willing and able to comply with protocol and undergo vigorous rehabilitation

• Signed informed consent

Exclusion Criteria:

• Multiple cartilage lesions of the knee, other location than femoral condyle (medial, lateral or trochlear), deeper than 6 mm, smaller than 1.5cm2 or greater than 7.5cm2, mild symptoms, caused by reason other than trauma or OCD, unstable knee, accompanying pathology other than 50% menisectomy.

• Hyaluronic acid knee injections in the past 3 months,

• History of chronic bone or cartilage disorder, bilateral knee pain and/or cartilage lesion

• History of any neoplastic disease, or chemotherapy treatment

• Chronic steroid intake, chronic pain medication use for conditions other than the involved knee, use of blood thinners (during the past 10 days prior to enrollment)

• History of allergy or atopic disease, sensitivity to blood products

• Evidence of any significant systemic disease, known coagulopathies or acute injury that might compromise the patient's welfare

• Pregnant or lactating women

• Substance or alcohol abuse

• Microfracture to the affected knee within the previous 2 years

• Participation in concurrent trials

• Participation in previous trials within 3 months

• Malignancy

• Taking specific drugs for osteoarthritis, such as chondroitin sulfate, diacerein, n-glucosamine, piaseledine, or capsaicin within 2 weeks of the baseline visit

• Chronic use of anticoagulants

• Uncontrolled diabetes

• Active joint infection

• Other unstable cardiac and pulmonary disorder

• Liver enzymes (SGOT, SGPT, alkaline phosphatase) of more then two times the upper limit of normal or any other results that in the clinical investigator's mind is important clinically

• Clinical and/or radiographic disease in the indexed affected joint that includes:

• Osteoarthritis or avascular necrosis

• Rheumatoid arthritis or a history of septic or reactive arthritis

• Gout or a history of gout or pseudogout in the affected knee

• Osteochondritis dissecans of the knee with significant bone loss

• Bipolar articular cartilage involvement (or kissing lesions) of the ipsilateral compartment (i.e >than ICRS grade 2 on the opposing articular surface)

• Associated damage to the underlying subchondral bone requiring an osteochondral graft

• History of secondary arthropathies (i.e. sickle cell disease, Hemochromatosis, or autoimmune disease)

• Receiving prescription pain medication other than NSAIDs or acetaminophen for conditions unrelated to the index knee conditions

• BMI >40 kg/m2

• Unable to undergo MRI

• Any reasons making the patient a poor candidate in the eyes of the investigator

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Symptomatic Cartilage Defects of the Femoral Condyle

Intervention

Biological:
• BioCart™II
A cartilage biopsy will be harvested from patients during arthroscopy and used for chondrocyte isolation, culture and future implantation. Subjects will also have about 80 ml venous blood drawn for autologous cell culture medium. Two-four weeks following biopsy harvest, BioCart™II will be implanted into the cartilage defect after careful debridement via miniarthrotomy.

Procedure:
• Microfracture
MF procedure will be carried out according to accepted practice. After careful debridement multiple perforations, or microfractures, are made in the subchondral bone using an awl. The released bone marrow forms a clot at the lesion site which is an enriched environment for new tissue formation. With the subject's consent a cartilage biopsy will be taken (at least 150 mg) and about 80 ml venous blood withdrawn. This will be used for chondrocyte culture and cryopreservation in case a later BioCart™II implantation is required after failure of the microfracture procedure.

Locations

Country	Name	City	State
Israel	Sheba Medical Center Tel Hashomer	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Assaf Harofeh Medical Center	Zerifin
United States	University Orthopedics Center	Altoona	Pennsylvania
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Mount Sinai Medical Center	New York	New York
United States	Southeastern Orthopedic Center	Savannah	Georgia
United States	Tucson Orthopaedic Institute	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
ProChon Biotech Ltd

Countries where clinical trial is conducted

United States,  Israel, 

References & Publications (2)

Domayer SE, Welsch GH, Nehrer S, Chiari C, Dorotka R, Szomolanyi P, Mamisch TC, Yayon A, Trattnig S. T2 mapping and dGEMRIC after autologous chondrocyte implantation with a fibrin-based scaffold in the knee: preliminary results. Eur J Radiol. 2010 Mar;73(3):636-42. doi: 10.1016/j.ejrad.2008.12.006. Epub 2009 Jan 20. — View Citation

Nehrer S, Chiari C, Domayer S, Barkay H, Yayon A. Results of chondrocyte implantation with a fibrin-hyaluronan matrix: a preliminary study. Clin Orthop Relat Res. 2008 Aug;466(8):1849-55. doi: 10.1007/s11999-008-0322-4. Epub 2008 Jun 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in the Lysholm joint function score of subjects in the BioCart™II study group compared with the MF study group		12 months with optional follow up to 5 years	Yes
Secondary	Improvement in clinical function post implantation/surgery compared to baseline in the study group and compared with the control group, of the following:		12 months with optional follow up to 5 years	No
Secondary	IKDC knee score		12 months with optional follow up to 5 years	No
Secondary	KOOS questionnaire		12 months with optional follow up to 5 years	No
Secondary	ICRS functional status		12 months with optional follow up to 5 years	No
Secondary	VAS pain score		12 months with optional follow up to 5 years	No