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

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.

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.

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.

All study personnel involved in the surgical procedure will be unblinded. Patient and outcomes evaluators will be blinded.

NTX-001 used during surgical repair of an upper extremity peripheral nerve injury in conjuction with standard suture neurorrhaphy.

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.

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.

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.

The MRCC motor measures the function of the muscles; on a scale from M0 to M5; the higher score indicates better strength.

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.

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.

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.

Ghergherehchi CL, Mikesh M, Sengelaub DR, Jackson DM, Smith T, Nguyen J, Shores JT, Bittner GD. Polyethylene glycol (PEG) and other bioactive solutions with neurorrhaphy for rapid and dramatic repair of peripheral nerve lesions by PEG-fusion. J Neurosci Methods. 2019 Feb 15;314:1-12. doi: 10.1016/j.jneumeth.2018.12.015. Epub 2018 Dec 23.

Mikesh M, Ghergherehchi CL, Louis Hastings R, Ali A, Rahesh S, Jagannath K, Sengelaub DR, Trevino RC, Jackson DM, Bittner GD. Corrigendum to "Polyethylene glycol solutions rapidly restore and maintain axonal continuity, neuromuscular structures, and behaviors lost after sciatic nerve transections in female rats.". J Neurosci Res. 2018 Sep;96(9):1623. doi: 10.1002/jnr.24277. No abstract available.

Mikesh M, Ghergherehchi CL, Rahesh S, Jagannath K, Ali A, Sengelaub DR, Trevino RC, Jackson DM, Tucker HO, Bittner GD. Corrigendum to "Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats". J Neurosci Res. 2018 Sep;96(9):1624. doi: 10.1002/jnr.24278. No abstract available.

Bittner GD, Spaeth CS, Poon AD, Burgess ZS, McGill CH. Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells. Neural Regen Res. 2016 Jul;11(7):1033-42. doi: 10.4103/1673-5374.187019.

Bittner GD, Sengelaub DR, Trevino RC, Peduzzi JD, Mikesh M, Ghergherehchi CL, Schallert T, Thayer WP. The curious ability of polyethylene glycol fusion technologies to restore lost behaviors after nerve severance. J Neurosci Res. 2016 Mar;94(3):207-30. doi: 10.1002/jnr.23685. Epub 2015 Nov 3.