Safety and Efficacy of NTX-001 Compared to SOC in Acute Single Peripheral Nerve Injuries

Study Overview
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Brief Summary
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NTX-001 is a single use surgical product intended for use in conjunction with standard suture neurorrhaphy of severed nerves in patients between 16 and 80 years of age.

Detailed Description
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NTX-001 (Product) is a surgical product that consists of an active solution (drug), an isolation chamber medical device (chamber or device) and two (2) other sterile solutions. NTX-001 has been developed as a surgical product to be used in conjunction with standard suture neurorrhaphy of a severed nerve. Use of NTX-001 is intended to safely accelerate the often slow and diminished return of function in repaired nerves. It often takes months and/or years to determine if function will be restored. By that point, restoration is often incomplete and can result in lifelong motor and/or sensory deficits. By reconnecting (PEG-fusion) a substantial number of axons within a severed nerve, the degeneration-regeneration cycle and subsequent atrophy may be reduced or even prevented for those axons and their targets, respectively. NTX-001 (PEG-fusion) has the potential to avoid the consequences of protracted denervation of distal target tissues by eliminating the period of total denervation thus reducing the time to stable recovery and providing greater innervation to affected tissues.

Official Title
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Phase 2a, Multicenter, Randomized, Patient and Evaluator Blinded, Controlled Study Evaluating the Safety and Efficacy of NTX-001 Compared to SOC in the Treatment of Acute Single Transected Peripheral Nerve Injury Occurring Below the Distal Border of the Brachial Plexus Requiring Surgical Repair.

Conditions
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Peripheral Nerve Injuries

Intervention / Treatment
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* Combination Product: NTX-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is at least 16 years of age and not older than 80. The subject has sustained a confirmed (intra-op assessment) single transected peripheral nerve injury. The subject's nerve injury is classified as Sunderland's Fourth and Fifth Degree (Class III) The subject's nerve injury is amenable to minimal or acceptable tension, in direct, end-to-end repair. The surgical repair will occur within 48 hours of injury. Exclusion Criteria: The subject has a PNI with a segmental loss (gap) that cannot be repaired with minimal or acceptable tension. Other treatments known to affect the growth and/or physiology of the neural and vascular system. The nerve injury has vascular damage that cannot be repaired to provide adequate perfusion of the injured site. The subject is pregnant and/or is breastfeeding. The subject has a significant medical comorbidity precluding immediate repair.

Ages Eligible for Study
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Minimum Age: 12 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: Treatment vs. Standard of Care
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NTX-001<br>NTX-001 used during surgical repair of an upper extremity peripheral nerve injury in conjuction with standard suture neurorrhaphy. | Combination Product: NTX-001<br>* One time use surgical product, 3 solutions applied topically, in sequence, to the peripheral nerve repair site, in conjunction with standard suture neurorrhaphy. An isolation chamber medical device (device) is utilized to focus the application of PEG (Solution #2) on the coapted nerve for the required amount of exposure time.<br>* Other names: PEG-fusion;|
| No Intervention: Standard of Care<br>standard suture neurorrhaphy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | An adverse event is any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given a study product or in a clinical study. A treatment-emergent adverse event was defined as any adverse event that newly appeared, increased in frequency, or worsened in severity on or after the exposure to the study product. | Up to 48 Weeks | 
| Michigan Hand Questionnaire Total Score (MHQ) | The MHQ measures hand function and is scored from 0-100; with 100 being the best score. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Pain Rating Scale (NPRS) | The NPRS measures pain intensity on a scale from 0 representing no pain and 10 to the worst pain as bad as you can imagine. | Weeks 4, 8, 12, 24, 36 and 48 | 
| Modified British Medical Research Council (MMRC) sensory grading (S0-S4) | The SWMT measures sensation as using a score from S0 to S4; higher score indicates better sensation. | Weeks 4, 8, 12, 24, 36 and 48 | 
| Modified British Medical Research Council (MMRC) motor grading (M0-M5) | The MRCC motor measures the function of the muscles; on a scale from M0 to M5; the higher score indicates better strength. | Weeks 4, 8, 12, 24, 36 and 48 | 
| Semmes-Weinstein Monofilament Test (SWMT) | The SWMT assesses sensation using using equipment that measures force felt in grams. | Weeks 4, 8, 12, 24, 36 and 48 | 
| Pinch Strength | The Pinch test assesses strength using using equipment that measures strength in pounds. | Weeks 4, 8, 12, 24, 36 and 48 | 
| Grip Strength | The Grip test assesses strength using using equipment that measures strength in pounds. | Weeks 4, 8, 12, 24, 36 and 48 | 
| Cold Intolerance Symptom Severity (CISS) | The CISS focuses on the impact of cold intolerance on activities of daily life; the score ranges a score between 0 and 10, where 0 is no symptoms at all and 100 is the most severe symptoms you can possibly imagine. | Weeks 4, 8, 12, 24 and 48 | 
| Patient Global Impression of Change (PGIC) | The PGIC measures information about the effect of a treatment intervention in an individual subject, scored 0 to 7; with 0 being the worst and 7 being the best. | Weeks 4, 8, 12, 24 and 48 |