Ixmyelocel-T Treatment of Patients With Osteonecrosis of the Femoral Head (ON-CORE)

Multi-center Clinical Trial of the Application of Ixmyelocel-T in the Treatment of Osteonecrosis of the Femoral Head

The purpose of this study is to determine if Ixmyelocel-T grafting with demineralized bone matrix bound in autologous plasma after core decompression surgery is superior to core decompression with demineralized bone matrix bound in autologous plasma in preventing progression of osteonecrosis to a more severe disease stage (Stage II to III or higher) from the time of surgery until 24 months later, in patients with University of Pennsylvania (UPenn) Stage IIB or C disease at diagnosis.

Study Overview

• Status: Completed
• Conditions: Osteonecrosis
• Intervention / Treatment: Biological: Ixmyelocel-T; Other: Standard of Care Only

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Department of Orthopaedic Surgery
  • New York
    • Brooklyn, New York, United States, 11220
      • Lutheran Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ixmyelocel-T; Core decompression & treatment with Tissue Repair Cells (TRCs), demineralized bone matrix bound in autologous plasma	Biological: Ixmyelocel-T; Core decompression of the femoral head to remove necrotic tissue with Ixmyelocel-T given to treatment arm only.
ACTIVE_COMPARATOR: Standard of Care Only; Core decompression, demineralized bone matrix bound in autologous plasma, without any TRCs.	Other: Standard of Care Only; Core decompression of the femoral head to remove necrotic tissue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The progression of patients with UPenn Stage IIB or IIC disease to a more severe stage based on all available x-ray and MRI imaging. Patients who have a definitive procedure but do not have a valid assessment will be considered to have progressed.	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to progression (in months)	24 months
Osteonecrosis volume measured by MRI	24 months
Pain and quality of life questionnaires	24 months

Collaborators and Investigators

• Sponsor: Vericel Corporation
• Investigators: Principal Investigator: Marc Hungerford, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (ACTUAL): September 1, 2010
• Study Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: July 20, 2007
• First Submitted That Met QC Criteria: July 20, 2007
• First Posted (ESTIMATE): July 23, 2007

Study Record Updates

• Last Update Posted (ACTUAL): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 11, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Osteonecrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Musculoskeletal Diseases; Bone Diseases; Femur Head Necrosis; Legg-Calve-Perthes Disease; Osteonecrosis
• Other Study ID Numbers: ABI 55-0705-1