Safety and Efficacy of Cethrin® in Adult Subjects With Acute Cervical Spinal Cord Injury

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind, placebo-controlled, Phase IIb study to be conducted in North America and Europe and will include male and female subjects with acute cervical SCI, 18 to 62 years of age, who receive clinical trial material (CTM) within 72 hours of injury. This study is being undertaken to evaluate and confirm the safety and efficacy of CETHRIN®. This adaptive study has been designed to efficiently identify the safest and most effective dose in Phase IIb which will be evaluated in a future Phase III study. Given the current lack of effective treatments for SCI, an improvement in motor ability or activities of daily living in these subjects would be a great advancement in the treatment of SCI.

Official Title
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A Phase IIb, Double-Blind, Randomized, Placebo Controlled, Multicenter Study to Assess the Safety and Efficacy of Intraoperative Epidural Cethrin® in Adult Subjects With Acute Cervical Spinal Cord Injury

Conditions
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Acute Cervical Spinal Cord Injury

Intervention / Treatment
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* Drug: Cethrin® (BA-210)
* Procedure: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand the requirements of the study, provide informed consent, agree to the study restrictions, and agree to return for the required assessments Males or females, 18 through 62 years of age, inclusive AIS Grade A, complete injury with the ability to obtain accurate baseline assessment Motor neurological level of C5, C6, or C7 Subjects with acute cervical SCI scheduled to receive decompression/stabilization surgery Must be willing and able to participate in study procedures and assessments Must be medically stable If of childbearing potential, women must agree to either of the following for the duration of the 12-month trial: (a) abstinence, or (b) if sexually active, to use one of the following methods of birth control: barrier with spermicide, intrauterine device, birth control hormones, or surgical sterilization Must provide witnessed verbal authorization for use and disclosure of protected health information (PHI) Exclusion Criteria: Subjects who have participated in a clinical trial involving investigational medications, devices or procedures within 30 days before administration of CTM Subjects who require the use of mechanical ventilation Females with a positive serum pregnancy test Females who are breastfeeding Preexisting SCI Subjects who are unable to receive study medication within 72 hours of injury Subjects with peripheral nerve injury, brachial plexus injury, or multifocal SCI Subjects with injuries that prevent a comprehensive ASIA assessment Complete spinal cord transection Acute SCI because of gun shot or knife wound Subjects who are mentally or medically unstable, or are otherwise unlikely to complete the trial in the judgment of the investigator Subjects who present with history of symptomatic cervical spondylotic myelopathy Subjects with moderate to severe traumatic brain injury with a Glasgow Coma Scale score of less than 14 History of multiple sclerosis or other neuromuscular disorder History of an adverse reaction to a fibrin sealant or its human or bovine components Clinically significant neurological, cardiac, respiratory, hepatic, or renal disease History of cancer (except for basal cell carcinoma) Hemophilia or other bleeding abnormality Ankylosing spondylitis Use of insulin therapy to control diabetes mellitus within 6 months of SCI Known immunodeficiency, including human immunodeficiency virus or use of immunosuppressive or cancer chemotherapeutic drugs Body mass index (BMI) of ≥40 kg/m2 at screening (Appendix B includes a table for height and weight to calculate BMI)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 62 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Procedure: placebo<br>* Spinal decompression surgery without administration of Cethrin® BA-210<br>|
| Experimental: 2<br>1mg Cethrin® | Drug: Cethrin® (BA-210)<br>* Intraoperative epidural administration during spinal decompression surgery<br>* Other names: Cethrin®;|
| Experimental: 3<br>3mg Cethrin® | Drug: Cethrin® (BA-210)<br>* Intraoperative epidural administration during spinal decompression surgery<br>* Other names: Cethrin®;|
| Experimental: 4<br>6mg Cethrin® | Drug: Cethrin® (BA-210)<br>* Intraoperative epidural administration during spinal decompression surgery<br>* Other names: Cethrin®;|
| Experimental: 5<br>12mg Cethrin®. Administration of this dose is dependent on data from lower doses. | Drug: Cethrin® (BA-210)<br>* Intraoperative epidural administration during spinal decompression surgery<br>* Other names: Cethrin®;|
| Experimental: 6<br>18mg Cethrin®. Administration of this dose is dependent on data from lower doses. | Drug: Cethrin® (BA-210)<br>* Intraoperative epidural administration during spinal decompression surgery<br>* Other names: Cethrin®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in ASIA motor score |  | week 26 | 
| Death |  | 12 months | 
| Serious Adverse Events |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ASIA Impairment Scale (AIS) grade |  | Week 4, Week 8, Week 16, Week 26, and Week 52 | 
| Total motor score, upper extremity motor score, and lower extremity motor score |  | Week 4, Week 8, Week 16, Week 26, and Week 52 | 
| Neurological motor level (right and left) and motor zone of partial preservation (ZPP) (right and left) |  | Week 4, Week 8, Week 16, Week 26, and Week 52 | 
| Change in motor score within the ZPP (right and left) |  | Week 4, Week 8, Week 16, Week 26, and Week 52 | 
| Spinal cord independence measure (SCIM) total score, subscores and individual items |  | Week 4, Week 8, Week 16, Week 26, and Week 52 | 
| Functional independence measure (FIM) total score, subscores and individual items |  | Week 4, Week 8, Week 16, Week 26, and Week 52 | 
| Adverse events |  | 12 months |