BMAC Nerve Allograft Study

Study Overview
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Brief Summary
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This study is a prospective, multi-center, proof of principle, phase I human safety study evaluating the sequential treatments of the Avance Nerve Graft, a commercially available decellularized processed peripheral nerve allograft, with autologous Bone Marrow Aspirate Concentrate (BMAC), a source of stem cells, for the repair of peripheral nerve injuries up to 7 cm in length. The purpose of this study is to establish a knowledge product, evaluating the safety profile of the Avance Nerve Graft, followed by the application of BMAC to support further investment into the promising area of using stem cells in conjunction with scaffolds.

Official Title
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Clinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Aspirate Concentrate (BMAC) to Improve Peripheral Nerve Repair and Functional Outcomes

Conditions
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Peripheral Nerve Injury Upper Limb

Intervention / Treatment
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* Procedure: Avance Nerve Graft with Autologous BMAC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant female 18 to 74 years of age. Undergoing peripheral nerve exploration or grafting with allograft in the upper extremity. Subjects must be inpatients or scheduled for surgery at the time of study enrollment. Has nerve conduction block injuries to the ulnar, median, radial or musculocutaneous nerve of either upper extremities that is less than two years from injury. Be willing to undergo tension free end-to-end nerve graft coaptation on both the proximal and distal portion of the nerve gap with the Avance Nerve Graft. Be willing to have bone marrow harvested from own body, concentrated, and applied to the site of nerve injury following the insertion of the Avance Nerve Graft. Be willing to participate and able to comply with all aspects of the treatment and evaluation schedule over a 18-month duration. Capable of giving their own consent to participate in the study, and willing to sign and date an IRB-approved written informed consent prior to initiation of any study procedures. Nerve conduction injury affecting sensory and motor function or solely motor function in the upper extremity. Nerve gaps following resection, up to 7 cm, inclusive. Exclusion Criteria: Subjects with Type 1 Diabetes Mellitus or Type 2 Diabetes Mellitus requiring regular insulin therapy. Subjects who are undergoing or expected to undergo treatment with chemotherapy, radiation therapy, or other known treatment which affects the growth of neural and/or vascular system. History of neurodegenerative disease, neuropathy, or diabetic neuropathy. History of chronic ischemic condition of the upper extremity. Cognitive limitation or mental illness preventing informed consent. Nerve injuries >2 years post initial injury. Any participant who at the discretion of the Investigator is not suitable for inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avance Nerve Graft with autologous BMAC<br>The Avance Nerve Graft will be inserted in the area of nerve injury. Between 40 to 60 ml of Bone Marrow Aspirate from the anterior or posterior iliac crest of the pelvis will be harvested . Using SmartPrep centrifuge and 60 ml BMAC kit, 7 to 10 ml of final BMAC will be obtained. | Procedure: Avance Nerve Graft with Autologous BMAC<br>* The Avance Nerve Graft will be inserted in the area of nerve injury. Between 40 to 60 ml of Bone Marrow Aspirate from the anterior or posterior iliac crest of the pelvis will be harvested. Using SmartPrep centrifuge and 60 ml BMAC kit, 7 to 10 ml of final BMAC will be obtained. Of the 7 to 10 ml of final BMAC that is yielded, half (3.5 to 5 ml) of the final concentrate, will be injected on top of the Avance Nerve Graft following coaptation. The second half (3.5 to 5 ml) of the final concentrate will be inserted into a sterile tube containing culture media and shipped overnight to Cleveland Clinic Lerner Research Institute for cell processing and colony assay to confirm that the BMAC indeed contains autologous bone marrow stem cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the nature and incidence of AEs between the group of subjects receiving Avance Nerve Graft with BMAC and the historical data of nerve repairs with the Avance Nerve Graft. | Long-term study associated AEs, such as infection, wound dehiscence, neuropathy, carpal tunnel syndrome, bleeding, seroma, and lymphocele will be captured and analyzed together with any change in incidence of listed AEs which may be precipitated by treatment. . AEs will be mapped to a MedDRA preferred term and system organ classification. The occurrence of the AEs will be summarized by repair type using MedDRA preferred terms, system organ classifications, and severity. All AEs will be listed for individual subjects showing both verbatim and preferred terms. Separate summaries of treatment-emergent SAEs and AEs related to repair will be generated. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Test of non-inferiority and superiority of Avance Nerve Graft to historical nerve autograft scores with respect to Rosen-Lundborg using closed testing procedures | Test of non-inferiority and superiority of Avance Nerve Graft to historical nerve autograft scores with respect to Rosen-Lundborg will be conducted using closed testing procedures. The hypotheses being tested are as follows: H01: Δ ≤ -Δ0 vs. H11: Δ > -Δ0 H02: Δ = 0 vs. H12: Δ ≠ 0 where Δ = μC- μA is the difference between the mean Rosen-Lundborg Scores for the Avance Nerve Graft & BMAC (μA) and the mean Rosen-Lundborg scores for the historical autograft controls (μC), Δ0 is the non-inferiority margin 0.51. The null hypothesis of non-inferiority (H01) will be tested first and, if rejected, then the null hypothesis of superiority (H02) will be assessed. Given that the closed testing procedure is implemented, no adjustment for multiple testing will be required. | 18 months | 
| Test of non-inferiority of Avance Nerve Graft plus BMAC to Avance Nerve Graft recovery rates with respect to Rosen-Lundborg scores using closed testing procedures | Test of non-inferiority of Avance Nerve Graft plus BMAC to Avance Nerve Graft recovery rates with respect to Rosen-Lundborg scores will be conducted using closed testing procedures. The hypothesis being tested is as follows: H01: πA - πAB > Δ vs. H11: πA - πAB < Δ where πA is the recovery of Avance Nerve Graft and πAB is the recovery of Avance plus BMAC. Δ is the non-inferiority margin 25% | 18 months |