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

Peripheral Nerve Injuries Clinical Trial

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04572906
• Other study ID #: NTx20201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 25, 2020
• Est. completion date: August 15, 2024

Study information

• Verified date: August 2023
• Source: Neuraptive Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 51
• Est. completion date: August 15, 2024
• Est. primary completion date: August 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Peripheral Nerve Injuries
• Wounds and Injuries

Intervention

Combination Product:
• NTX-001
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.

Locations

Country	Name	City	State
United States	Curtis National Hand Center	Baltimore	Maryland
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	University of Chicago	Chicago	Illinois
United States	The Ohio State University Wexner Medical Center Hand and Upper Extremity Center	Columbus	Ohio
United States	UF Health - University of FL - Gainesville	Gainesville	Florida
United States	Indiana Hand to Shoulder Center	Indianapolis	Indiana
United States	Orlando Health	Orlando	Florida
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University	Saint Louis	Missouri
United States	Harborview Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Neuraptive Therapeutics Inc.

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Pinch Strength	The Pinch test assesses strength using using equipment that measures strength in pounds.	Weeks 4, 8, 12, 24, 36 and 48
Secondary	Grip Strength	The Grip test assesses strength using using equipment that measures strength in pounds.	Weeks 4, 8, 12, 24, 36 and 48
Secondary	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
Secondary	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