Official Title: “A Dose-Escalation Study to Assess the Feasibility and Safety of 3 Different Doses of NeoFuse When Combined With MasterGraft Granules in Subjects Requiring Posterolateral Lumbar Fusion With Instrumentation.”

This is a first-in-human, dose escalation clinical study to evaluate the feasibility, safety, and tolerability of 3 different doses of immunoselected, culture-expanded, nucleated, allogeneic MPCs (NeoFuse) when combined with MasterGraft Resorbable Ceramic Granules (Medtronic Sofamor Danek USA, Inc.) compared to autograft in patients requiring posterior lumbar interbody fusion with NuVasive's radiolucent PEEK OPTIMA cage (to be used with autologous bone graft material) and 1 or 2 level posterolateral lumbar fusion surgery with instrumentation. The instrumentation used for this study will be the Monarch® 5.50 mm Spine System (DePuy).

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety Study

Study Primary Completion Date: May 2010

Intervention(s) in this Clinical Trial

• Genetic: NeoFuse
  • immunoselected, culture-expanded, nucleated, allogeneic MPCs (NeoFuse) combined with MasterGraft Resorbable Ceramic Granules in subjects requiring posterior lumbar interbody fusion with NuVasive's radiolucent PEEK OPTIMA cage
• Procedure: posterolateral spinal fusion with instrumentation
  • autograft in subjects requiring posterior lumbar interbody fusion with NuVasive's radiolucent PEEK OPTIMA cage

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • 10 subjects to receive lowest dose of NeoFuse
• Active Comparator: 2
  • 4 subjects standard posterolateral spinal fusion with instrumentation
• Experimental: 3
  • 10 subjects to receive middle dose of NeoFuse
• Active Comparator: 4
  • 3 subjects standard posterolateral spinal fusion with instrumentation
• Experimental: 5
  • 10 subjects to receive highest dose of NeoFuse
• Active Comparator: 6
  • 3 subjects with standard posterolateral spinal fusion with instrumentation

Primary Measures

• To determine the safety of NeoFuse (allogeneic mesenchymal precursor cells [MPCs]) when combined with MasterGraft Resorbable Ceramic Granules as a carrier for posterolateral lumbar fusion with instrumentation.
  • Time Frame: 30 days
    Safety Issue?: Yes

Secondary Measures

• To evaluate the overall fusion success of the use of NeoFuse plus carrier compared to autograft in the same patient
  • Time Frame: 3 years
    Safety Issue?: No
• To assess CT scan as a pilot measure of fusion for use in the pivotal study
  • Time Frame: 3 years
    Safety Issue?: No
• To provide preliminary data to support dose selection
  • Time Frame: 3 years
    Safety Issue?: No

Inclusion Criteria:

• 1. Men and women ≥ 18 years of age.
• 2. Must have DDD in 1or 2 adjacent vertebral levels between L1 and S1 confirmed by computerized tomography (CT), magnetic resonance imaging (MRI), discography, plain film, or myelography with presence of radiculopathy and instability;WITH OR WITHOUT UP
• TO AND INCLUDING Grade II spondylolisthesis in 1 or 2 adjacent vertebral levels between L1 and S1 as defined by the Meyerding grading method, whereas the degree of slippage is measured as the percentage of distance the anteriorly translated vertebral body has moved forward relative to the superior end plate of the vertebrae below.5
• Grade I represents 1% to 25% slippage. Grade II represents 26% to 50% slippage.
• 3. May also have coexistent spinal or foraminal stenosis as confirmed by MRI or CT evaluation.
• 4. Must have clinical symptoms of neurogenic claudication as evidenced by leg pain, weakness, sensory changes and diminished reflexes brought on by walking, standing, or increased lumbar lordosis and relieved by bending or sitting.
• 5. Must have failed 6 months of nonoperative management consisting of supervised physical therapy and pain control.
• 6. Must be a candidate for lumbar interbody fusion in combination with posterolateral lumbar fusion with the use of autograft from the iliac crest requiring a 1 or 2-level fusion of adjacent vertebral levels between L1 and S1.
• 7. Must be willing and able to understand, sign, and date the Informed Consent Form.
• 8. Female subjects of childbearing age or potential and male subjects with partners of childbearing potential must be willing to use adequate contraception (hormonal or barrier method or abstinence) from the time of screening and for a period of at least 1 year after surgery.
• 9. Female subjects of childbearing potential must have a negative serum pregnancy test at screening (within 2 weeks of surgery) and a negative urine pregnancy test on the day of surgery.
• 10. Must have an Oswestry Low Back Pain Disability questionnaire score at screening of ≥ 30%.
• 11. Must not have history of drug or alcohol abuse within 1 year of study enrollment, as determined by the investigator.
• 12. Must meet the following laboratory criteria:
• Platelet count ≥ 100,000 cells/μL
• Hemoglobin ≥ 9.0 g/dl
• Prothrombin time (PT) or international normalized ratio (INR) and partial thromboplastin time (PTT) , <1.5x ULN within 4 hours prior to the surgical procedure
• Aspartate transferase (AST)/alanine transferase (ALT) ≤ 1.5x ULN
• Creatinine ≤ 1.5 mg/dl
• 13. Must have a stable screening electrocardiogram (ECG), as determined by the investigator that would not preclude surgery.
• 14. Must be willing to return for required follow-up visits.
• 15. Must be able to follow postoperative management program.

Exclusion Criteria:

• 1. Is pregnant or breastfeeding.
• 2. Has an active systemic infection or infection at the site of the surgery.
• 3. Has Grade III or greater spondylolisthesis.
• 4. Has or is undergoing revision of a prior fusion at the involved levels.
• 5. Has a history of epidural steroid injections within 1 week prior to study treatment.
• 6. Has a history of hypersensitivity or anaphylactic reaction to murine or bovine products, dimethyl sulfoxide (DMSO), or titanium.
• 7. Has MRI or CT that shows greater than 50% anterior translocation of cranial vertebral body or greater than 20 degree angular motion of the listhesis segment.
• 8. Has a history of active malignancy in the last 5 years, other than basal cell carcinoma.
• 9. Has osteoporosis as defined by a dual energy x-ray absorptiometry (DXA T) score of ≤
• 3.5 or a history of fragility fractures or other significant bone disease contraindicating the use of spinal instrumentation.
• Note: subjects will be screened using the Simple Calculated Osteoporosis Risk
• Evaluation (SCORE) osteoporosis questionnaire.
• 10. Has a history of Paget's disease of the spine, osteomalacia, or any other metabolic bone disease.
• 11. Has a history of prior radiotherapy to the involved area.
• 12. Has received systemic corticosteroids at a dose equivalent to prednisone > 10 mg/day within 14 days prior to study procedure.
• 13. Has received systemic nonsteroidal anti-inflammatory drugs (NSAIDS) within 48 hours prior to study procedure, and unwilling to refrain from NSAIDS for the first 6 months following the procedure.
• 14. Has a positive screen for hepatitis B virus (HBsAg [hepatitis B virus surface antigen]), hepatitis C virus (anti-HCV [hepatitis C virus antibody]), or human immunodeficiency virus (HIV) antibodies.
• 15. Has had treatment with any investigational therapy administered within 6 months before implantation surgery. .
• 16. Is the prior recipient of allogeneic stem cell/progenitor cell therapy.
• 17. Has a diagnosis of uncontrolled diabetes, multiple sclerosis, or any concurrent medical condition that would affect the investigator's ability to evaluate the subject's condition or could compromise the subject's safety.
• 18. Is incarcerated at the time of enrollment.
• 19. Has a body mass index (BMI) > 35.
• 20. Has 20% or greater anti-human leukocyte antigen (HLA) antibody titer and/or has antibody specificities to donor HLA antigens.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Mesoblast, Ltd.

Overall Clinical Trial Officials and Contacts

Donna Skerrett, MD Study Director Mesoblast, Ltd.  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00549913

Study ID Number: MSF0106

ClinicalTrials.gov Identifier: NCT00549913

Health Authority: United States: Food and Drug Administration