Clinical trial NCT04572906: Safety and Efficacy of NTX-001 Compared to SOC in Acute Single Peripheral Nerve Injuries
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peripheral Nerve Injuries
Lead sponsor: Neuraptive Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-01
Enrollment: 51
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Treatment vs. Standard of Care
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* The subject is at least 12 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
timeFrame: Up to 48 Weeks
measure: Michigan Hand Questionnaire Total Score (MHQ)
timeFrame: Week 12
Secondary outcomes:
measure: Numeric Pain Rating Scale (NPRS)
timeFrame: Weeks 4, 8, 12, 24, 36 and 48
measure: Modified British Medical Research Council (MMRC) sensory grading (S0-S4)
timeFrame: Weeks 4, 8, 12, 24, 36 and 48
measure: Modified British Medical Research Council (MMRC) motor grading (M0-M5)
timeFrame: Weeks 4, 8, 12, 24, 36 and 48
measure: Semmes-Weinstein Monofilament Test (SWMT)
timeFrame: Weeks 4, 8, 12, 24, 36 and 48
measure: Pinch Strength
timeFrame: Weeks 4, 8, 12, 24, 36 and 48
measure: Grip Strength
timeFrame: Weeks 4, 8, 12, 24, 36 and 48
measure: Cold Intolerance Symptom Severity (CISS)
timeFrame: Weeks 4, 8, 12, 24 and 48
measure: Patient Global Impression of Change (PGIC)
timeFrame: Weeks 4, 8, 12, 24 and 48
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: UF Health - University of FL - Gainesville
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hand to Shoulder Center
state: Indiana
city: Baltimore
country: United States
facility: Curtis National Hand Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center Hand and Upper Extremity Center
state: Ohio
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
Study officials:
affiliation: Neuraptive Therapeutics Inc.
name: Seth Schulman, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.