Ixmyelocel-T Treatment of Patients With Osteonecrosis of the Femoral Head

This study is an event-driven, multi-center, prospective, independent observer-blinded, controlled, randomized Phase III clinical trial enrolling patients diagnosed with University of Pennsylvania (Steinberg) Classification Stage IIB or C osteonecrosis of the femoral head.

• The first patient group is the Treatment Group and will receive core decompression and treatment with BRCs and demineralized bone matrix bound in autologous plasma, and
• The second patient group is the Control Group and will receive core decompression and demineralized bone matrix bound in autologous plasma, without any BRCs.
• Enrollment: With an anticipated drop-out rate of 10% in up to twenty (20) sites, a total of approximately 135 patients will be enrolled and randomized to obtain 120 evaluable patients (75 for the TRC treatment group and 45 for the Control treatment group).
• Primary endpoint: The percentage of patients progressing to a more severe UPenn disease stage (Stage II to III or higher) between 0 and 24 months will be the primary efficacy variable to demonstrate TRC therapy is superior to Control therapy.

Inclusion criteria

• UPenn (Steinberg) classification of osteonecrosis, inclusive of Stages IIB and IIC. Diagnosis will be based on magnetic resonance imaging (MRI).
• Modified index of necrotic extent < 40
• Idiopathic and non-idiopathic osteonecrosis.
• No infection in affected bones at the time of surgery.
• Patient competent to give informed consent.
• Normal organ and marrow function defined as:

• Leukocytes ≥ 3000/µL;
• Absolute neutrophil count ≥ 1500/µL;
• Platelets ≥ 140,000/µL;
• Serum AST (SGOT)/ALT (SGPT) < 2.5 X institutional standard range;
• Serum creatinine within normal limits, based on clinical laboratory normal range.
• Female patients not pregnant or lactating.
• Patients with a history of corticosteroids or on active therapy, will only be eligible for enrollment if corticosteroid use is suspended for 1 month prior and 6 months after cell therapy and surgery.
• Patients who have been treated with oral bisphosphonates are eligible for the trial if treatment was stopped at least 6 months prior to enrollment.

Exclusion criteria

• Stages IA, IB, IC, IIA, IIIA or more severe femoral head osteonecrosis, primarily based on diagnosis by MRI.
• Flattening of the femur head (UPenn Stage IV) or articular cartilage collapse at the time of core decompression surgery.
• Septic arthritis; stress fracture, or non-osteonecrosis metabolic bone diseases (e.g., Paget's disease of bone, osteogenesis imperfecta, primary hyperparathyroidism, fibrous dysplasia [monostotic, polyostotic McCune-Albright syndrome] and osteopetrosis).
• Any active bisphosphonate treatment or any history of intravenous (IV) treatment
• HIV, syphilis, positive at time of screening.
• Active hepatitis B or hepatitis C infection at the time of screening
• Known allergies to protein products (horse or bovine serum, or porcine trypsin).
• Patients who will require continuous, systemic, high dose corticosteroid therapy (more than 7.5 mg/day) within 6 months after surgery.
• Patients in active treatment for cancer or blood dyscrasia, or have received chemotherapy, radiotherapy or immunotherapy in the past 2 years.
• Immunodeficiency diseases.
• Participation in another clinical study in the past 30 days or concurrent participation in another clinical trial.
• History of regular alcohol consumption exceeding 2 drinks/day (1 drink = 5 oz [150 mL] of wine or 12 oz [360 mL] of beer or 1.5 oz [45 mL] of hard liquor) within 6 months of screening and/or history of illicit drug use.
• MRI-incompatible internal devices (pacemakers, aneurysm clips, etc)
• Body mass index (BMI) of 40 Kg/m2 or greater
• Patients unable to tolerate general anesthesia defined as an American Society of Anesthesiologists (ASA) criteria of > 2
• Patients with poorly controlled diabetes mellitus (HbA1C > 8%), or with peripheral neuropathy, or known concomitant vascular problems.
• Patients receiving treatment with hematopoietic growth factors or anti-vasculogenesis or anti-angiogenesis treatment
• Traumatic osteonecrosis