Evaluating the Safety and Efficacy of Polyethylene Glycol (PEG) Mediated Fusion (PEG Fusion)

Study Overview
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Brief Summary
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The overall objective of this study is to determine the safety of PEG fusion when used with primary repair or reconstruction in patients with an acute upper extremity peripheral nerve injury. PEG is safe and effective for extending the half-life of circulating pharmaceutical products, when used in conjunction with a topical hemostatic agent in surgical wounds, and when used as a colon cleanser for endoscopic surgical procedures. However, PEG fusion has not been rigorously tested as a safe reagent to promote nerve regeneration in humans. Therefore, the goal of this Phase 2a clinical trial is to establish safety data and to examine the effect of PEG fusion on clinical outcomes including recovery of sensory and motor function. Results will be externally validated using data collected in the DoD funded prospective NERVE study and will provide preliminary evidence to power a larger phase II efficacy trial.

Detailed Description
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The study will enroll 40 patients receiving autograft reconstruction within 24 hours of injury. Patients will be randomized to either PEG mediated reconstruction (n=20); or conventional nerve reconstruction (n=20). The investigators hypothesize that (1) the rate of complications within 1 month of surgery in patients treated with PEG fusion will be comparable to that of patients treated with conventional autograft reconstruction, (2) there will be no detrimental effects from PEG fusion on nerve regeneration over 2 years compared to patients treated with conventional nerve reconstruction, ((3) recovery of sensory and motor function will occur earlier (within 6 months) among patients treated with PEG fusion compared to patients treated with conventional autograft reconstruction (4) patients treated with PEG fusion will have better range of motion, greater hand strength, less disability, less pain, and higher rates of treatment satisfaction compared with patients treated with conventional autograft reconstruction.

Official Title
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A Phase 2a Multicenter Randomized Controlled Trial Evaluating the Safety and Efficacy of Polyethylene Glycol (PEG) Mediated Fusion (PEG Fusion) Compared to Standard of Care in the Repair of Mixed Motor-sensory Acute Peripheral Nerve Injuries (PNI) for Rapid and Immediate Improvement in Outcome

Conditions
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Peripheral Nerve Injuries

Intervention / Treatment
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* Drug: NTX-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 18-80 Sustained a complete peripheral nerve injury resulting from upper extremity trauma presenting within 48 hours of injury Involves injury or dysfunction to motor and/or sensory function of the axillary, radial, median, ulnar, or musculocutaneous nerve with injury localized between the proximal humerus and the distal flexion crease of the wrist Involves a mixed nerve segment (i.e., involves a location of any of the above specified nerves that can be expected to have both sensory and motor axons present). Exclusion Criteria: Patients beginning surgery within hours after injury. Injury to the brachial plexus nerves Injury to the nerves distal to the distal flexion crease of the wrist Injury that involves a distal extension of the parent nerve that is considered sensory only (superficial radial nerve, lateral antebrachial cutaneous nerve, etc.) or the posterior interosseus or anterior interosseus nerve distal to the midpoint of the forearm (i.e., distal to what can be considered the main motor branches of the PIN and AIN). Previous peripheral nerve injury resulting from trauma, stroke, muscular, neurologic, or neuromuscular disorder Documented psychiatric disorder that is expected to result in high probability of self-harm or interfere with study follow-up. Severe problems with maintaining follow up (e.g., patients who are prisoners or homeless at time of injury or who are intellectually challenged without adequate family support). Not expected to survive the next 30 days due to their injuries/health condition. The subject has a known allergy to polyethylene glycol (PEG). If any of the assessments cannot be done on the contralateral side (CL) or the MRCC sensory 2PD value is > 10 mm on the CL side during baseline period, the subject is a screen failure. The subject is pregnant and/or is breastfeeding. The subject has a significant medical comorbidity precluding immediate repair. The subject is not able to strictly adhere to the rules of the current clinical protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: The study will enroll 40 patients receiving autograft reconstruction within 24 hours of injury. Patients within each group will be randomized to either PEG mediated reconstruction (n=20); or conventional nerve reconstruction (n=20).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG mediated reconstruction<br>NTX-001 will be administered topically via isolation chamber medical device. Dose Unit: 2.5 mL NTX-001 is a single use surgical product intended for use as adjunct treatment in the repair of severed peripheral nerves in patients requiring standard suture neurorrhaphy. | Drug: NTX-001<br>* • PEG fusion is the application of a polyethylene glycol (PEG) using a combination of sequenced reagents to a freshly performed nerve coaptation, or neurorrhaphy, to allow the axonal membranes of the proximal and distal axonal stumps to fuse back together and re-establish full axonal continuity.<br>|
| No Intervention: Conventional nerve reconstruction<br>Conventional nerve reconstruction | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complications or problems that occur with in the first 30 days. | Complications or problems include surgical site infections, wound dehiscence/breakdown, exposure of nerves and/or their repairs and reconstructions, breakdown of nerve repair or reconstruction, seroma/hematoma requiring an additional procedure to treat, and any other local wound complications related to the zone of nerve injury that require an additional surgical procedure | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensory Function | Sensory function will be evaluated using the the touch test mono-filament hand evaluation kit. | Up to 2 years | 
| Motor Function | Motor function will be evaluated using the British Medical Research Council motor grading scale. Motor is evaluated on a scale of M0 and M5, where M5 is the highest score and M0 is the lowest. | Up to 2 years | 
| Range of Motion | ROM will be measured using a standard goniometer. | Up to 2 years | 
| Grip Strength | Grip strength is assessed using a hand-held Jamar dynamometer. | Up to 2 years | 
| Pain Score | Self reported outcomes using the Brief Pain Inventory. | Up to 2 years | 
| Patient Satisfaction with Treatment | Patient Satisfaction with Treatment is measured using the Short Form Patient Satisfaction Questionnaire (PSQ-18) at 24 months following injury. | Up to 2 years |