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