Safety and Efficacy Study of NeoFuse in Subjects Undergoing Multi-Level Anterior Cervical Discectomy and Fusion

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and preliminary efficacy of NeoFuse in subjects with a diagnosis of degenerative disc disease (DDD) at 2 or more adjacent cervical vertebral levels between C3-C4 to C7-T1. All subjects in this study will undergo 2 or 3 level anterior cervical discectomy and fusion with Anterior Cervical Plate Fixation.

Detailed Description
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This is a prospective, multicenter, randomized, single-blinded, controlled study evaluating safety and preliminary efficacy of immunoselected, culture-expanded, nucleated, allogeneic MPCs (NeoFuse) combined with MasterGraft Matrix in a commercially available PEEK cervical Spacer compared to an active control in subjects undergoing 2 or 3 level anterior cervical discectomy and fusion with anterior cervical plate fixation. After the screening and surgical visits, each subject will be evaluated clinically and radiographically within 3 days and 30 days after surgery, and at 3, 6, 12, and 24 months after surgery. Subjects will be evaluated at the same time points for safety.

Official Title
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Phase 2 Study Evaluating Safety and Preliminary Efficacy of NeoFuse When Combined With MasterGraft Matrix in Subjects Undergoing Multi-Level Anterior Cervical Discectomy and Fusion With Anterior Cervical Plate Fixation

Conditions
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Cervical Degenerative Disc Disease, Degenerative Spondylolisthesis, Spinal Stenosis

Intervention / Treatment
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* Biological: NeoFuse
* Device: MasterGraft Granules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or females between 18 and 70 years of age, inclusive. Has the ability to understand the requirements of the study, to provide written informed consent, and to comply with the study protocol. Has the ability to understand and provide written authorization for the use and disclosure of personal health information (PHI). Has a documented symptomatic diagnosis of DDD at C3-C4 to C7-T1. Has symptomatic radiculopathy and/or myelopathy correlating to radiographic findings of duration of 6 weeks or greater that had failed to respond to non-operative management Is a candidate for anterior cervical discectomy and fusion in two or three adjacent cervical interbody levels between C3-C4 to C7-T1 Has a stable screening electrocardiogram (ECG), as determined by the investigator that would not preclude surgery. Exclusion Criteria: Female subjects who are pregnant or nursing, or women planning to become pregnant during the first year (12 months) following surgery. Has a current or prior history within the last 3 years of neoplasm (excluding basal cell carcinoma) and/or any active neoplasm within the last 24 months, prior to screening. Has at the time of surgery a systemic or local infection at the site of proposed surgery. Has or is undergoing revision of a prior fusion surgery at any involved level. Requires ACDF at only one cervical interbody level or more than 3 adjacent cervical interbody levels. Requires ACDF without the use of an anterior cervical plating system. Has osteoporosis as defined by a DEXA T score of ≤ -3.0 or a history of fragility fractures or other significant bone disease contraindicating the use of spinal instrumentation. Has a documented medical history or radiographic evidence of a metabolic bone disease or other condition which would negatively impact the bone healing process. Has a positive screen for human immunodeficiency virus (HIV) antibodies. Has had treatment with any investigational therapy or device within 6 months of study surgery and/or plans to participate in any other allogeneic stem cell/progenitor cell therapy trial during the 2-year follow-up period. Has been a recipient of prior stem cell/progenitor cell therapy for spinal fusion surgery. Has 20% or greater anti-human leukocyte antigen (HLA) antibody titer and/or has antibody specificities to donor HLA antigens. Is transient or has been treated in the last 6 months before enrollment for alcohol and/or drug abuse in an inpatient substance abuse program.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects received treatment in one of two parallel arms. Treatment Arm 1; NeoFuse (a biologic, consisting of STRO-3 immunological selected allogeneic Mesenchymal Precursor Cells, derived from adult bone marrow mononucleated cells) with Mastergraft Matrix (a medical device that is compression resistant and embedded with Mastergraft Granules). Subjects received 10 million Neufuse cells per treated cervical interbody level involved in the fusion. Either 2 or 3 levels were involved for a total of either 20 million or 30 million Neofuse cells. Treatment Arm 2; Mastergraft Granules (medical device made of medical grade combination of hydroxyapatite and beta-tricalcium phosphate).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NeoFuse<br>Anterior Cervical Discectomy and Fusion with NeoFuse. NeoFuseTM is constituted of STRO-3 immunological selected allogeneic MPCs, which are derived from adult bone marrow mononucleated cells that are culture-expanded and subsequently cryopreserved. The allogeneic MPCs are formulated in concentrations of nucleated cells in a 5 mL volume and are cryopreserved in 7.5% dimethyl sulfoxide (DMSO)/50% Alpha Modified Eagle's Medium (MEM) and 42.5% ProFreeze®. The final formulation consists of 0.15mL (approximately 10 million MPCs) of thawed NeoFuse™ thawed NeoFuseTM combined with the amount of MasterGraftTM Matrix to fill the PEEK cage per ACDF level. | Biological: NeoFuse<br>* Single Dose NeoFuse Surgical Implantation<br>* Other names: Adult Stem Cells;|
| Active Comparator: MasterGraft Granules<br>Anterior Cervical Discectomy and Fusion with MasterGraft Granules MASTERGRAFT® GRANULES are a medical-grade, polyporous resorbable ceramic hybrid composed of 15% hydroxyapatite (HA) and 85% beta-tricalcium phosphate (β-TCP). The combination of these natural bone materials provides surgeons with an osteoconductive, porous implant that improves osteointegration by allowing cells to colonize throughout the implant and optimize the bone healing process | Device: MasterGraft Granules<br>* Single Dose MaterGraft Granules Surgical Implantation<br>* Other names: Active Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of NeoFuse | To determine the safety of NeoFuse using physical examinations, vital signs, treatment emergent adverse events (TEAEs), and the results of clinical lab tests (hematology, serum chemistry, inflammation, and and immunology). | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fusion success with NeoFuse | To evaluate the fusion success with NeoFuse compared to an active control using CT scans and x-ray of the involved cervical spine levels and assess the change in outcomes (NDI, SF-36, Zung Depression Questionnaire, and WPAI. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervical Degenerative Disc Disease, Degenerative Spondylolisthesis, Spinal Stenosis, Stem cells, Adult Stem Cells, Anterior cervical discectomy and Fusion (ACDF), Anterior Cervical Plate Fixation