A Prospective, Randomized, Assessor-Blinded, Multicenter Study Comparing Avance Nerve Graft and Autograft for Functional Recovery Following Mixed and Motor Peripheral Nerve Reconstruction (Nerve-RESTORE℠)

This is a multicenter, 1:1 randomized, prospective, comparative study in participants requiring reconstruction of a mixed or motor nerve in the upper extremity. This study will consist of a screening visit, an operative visit, and 9 post-operative follow-up visits at Week 4, and Months 3, 6, 9, 12, 15, 18, 21, and 24.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Nerve Injury; Peripheral Nerve Discontinuity; Mixed Peripheral Nerve Injury; Motor Peripheral Nerve Injury; Upper Extremity Nerve Injury
• Intervention / Treatment: Biological: Avance Nerve Graft; Procedure: Sural nerve autograft

Detailed Description

This is a multicenter, 1:1 randomized, prospective, evaluator blinded, comparative study in participants requiring reconstruction of a mixed or motor nerve in the upper extremity. The study will assess recovery of motor and sensory function via MRCC score for nerve repairs with Avance Nerve Graft (Study Treatment) and sural nerve autograft (Comparator) through non-inferiority analyses. Participants will be considered enrolled to the study once all screening and eligibility criteria have been met and the participant has been centrally randomized to either Avance Nerve Graft or sural nerve autograft; Inclusion and exclusion criteria are defined at decision points for pre-operative screening eligibility and operative eligibility. This study will consist of a screening visit, an operative visit, and 9 post-operative follow-up visits at Week 4, and Months 3, 6, 9, 12, 15, 18, 21, and 24.

• Study Type: Interventional
• Enrollment (Estimated): 178
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Stacy Arnold; Phone Number: (386) 462-6800; Email: clinicalresearch@axogeninc.com
• Study Contact Backup: Name: Hayley Nicolosi; Phone Number: (386) 462-6800; Email: hnicolosi@axogeninc.com

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • OrthoIndy
      • Contact: Melanie Glover; Phone Number: 317-802-2880; Email: mglover@orthoindy.com
      • Principal Investigator: Brandon Smetana, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Study Participant Criteria

1. Be ≥ 18 years of age at the time of consent;
2. Willing and able to comply with all aspects of the treatment and evaluation schedule over a 24-month duration;

3. Provide documented Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent prior to initiation of any study procedures;

   Injury/Repair Criteria for Each Nerve

4. Primary or secondary nerve injury repair with sural nerve autograft or Avance Nerve Graft for fully transected reconstruction of the following upper extremity mixed and/or motor nerve(s):

   • Median nerve: proximal nerve stump within 20 cm from the center point of the thenar eminence and distal to the crease of the elbow;
   • Anterior interosseous nerve;
   • Median nerve recurrent motor branch;
   • Radial nerve: proximal nerve stump within 20 cm of the center of the forearm (midpoint between the tip of the olecranon and the styloid process) and distal to the mid-humerus;
   • Posterior interosseous nerve.
5. Zone of injury of eligible nerve(s) resectable to healthy nerve both distally and proximally and within the anatomical regions of Inclusion Criterion #4;
6. In study participants with multiple eligible nerve repairs, repair of all eligible nerves completed with the same study treatment, either Avance Nerve Graft or sural nerve autograft;
7. Measured nerve gap(s) following resection > 25 mm;
8. Nerve(s) repaired ≤ 120 days post injury;
9. Undergo coaptation on both the proximal and distal portion of the nerve gap(s) per the USPI for Avance Nerve Graft and per standard of care for sural nerve autograft; and
10. Either treatment method, Avance Nerve Graft or sural nerve autograft, is a viable option for all eligible nerve repair(s) (i.e., volume of injured nerve[s] does not exceed availability of sural nerve autograft for reconstruction, study participants are not treated with a combination of treatment types).

Exclusion Criteria:

Study Participant Criteria

1. Currently enrolled in another clinical study that may interfere with treatment, assessment of recovery, or participation in this study;
2. Deformities or injuries of the limb, hand, or digits that affect both the primary and secondary assessments for eligible nerve repair(s);
3. History of neuropathy of any etiology, diabetic neuropathy or any other known neuropathy including compressive/traumatic neuropathies affecting the target limb;
4. History of progressive neurodegenerative or autoimmune disorder affecting peripheral nerve or motor function (e.g., amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease);
5. History of chronic ischemic condition of the upper extremity;
6. Expected use of medication during the study that is known to impact nerve regeneration or to cause peripheral neuropathy;
7. Undergoing or expected to undergo treatment with chemotherapy, radiation therapy, or other known treatment which affects the growth of neural and/or vascular systems;

8. Participant is unlikely to comply with all study requirements and standard medical care procedures for the duration of the study schedule;

   Injury/Repair Criteria for Each Nerve

9. Median nerve repairs where the ulnar nerve has been transected due to injury or repair;
10. Repair(s) of a sensory-only proximal nerve stump;
11. Incomplete nerve transections;
12. Multilevel nerve injury pattern requiring two or more isolated reconstructions along the nerve pathway (for example, reconstruction of median nerve in forearm and recurrent motor branch resulting in repair pattern of graft to native nerve to graft to distal target);
13. Inadequate soft tissue coverage or extensive soft tissue injury which will impair recovery assessment;
14. Nerve avulsion injuries and nerve traction injuries resulting in rupture of the nerve;
15. Replantation/amputation of the limb, hand, or digits involved in both the primary and secondary assessments for eligible nerve repair(s);
16. Nerve repairs utilizing either end-to-side or side-to-side coaptation techniques;
17. Nerve transfer, tendon transfer, or other concomitant treatment at the time of nerve repair that affects assessment of function of the innervated muscle organ;
18. Use of coaptation devices that include metallic components or activated polymers and coaptations completed with fibrin glue only; and
19. Injuries with vascular damage resulting in inadequate perfusion despite repair (i.e., both radial and ulnar arteries injured [one injured artery is allowed]).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Avance Nerve Graft; Study Treatment: Avance Nerve Graft repairs of mixed or motor nerves (> 25 mm gaps)	Biological: Avance Nerve Graft; A commercially available, sterile, single-use peripheral nerve scaffold indicated for the treatment of functional deficits, manufactured from decellularized and sterilized extracellular matrix derived from human peripheral nerve tissue.; Other Names: Acellular nerve allograft-arwx
Active Comparator: Sural nerve autograft; Comparator: Sural nerve autograft repairs of mixed or motor nerves (> 25 mm gaps)	Procedure: Sural nerve autograft; A patient's own peripheral nerve tissue harvested in a secondary surgical procedure of the lower extremity where a functioning sural nerve is sacrificed for use in the reconstruction of a nerve defect.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery of motor function	Medical Research Council Classification (MRCC) of motor recovery score. This is an ordinal scale from M0-M5, with grade M0 meaning no contraction and M5 meaning full recovery in all muscles.	Assessed at 24 months
Recovery of sensory function	Medical Research Council Classification (MRCC) of sensory recovery score. This is an ordinal scale from S0-S4, with grade S0 meaning absence of sensibility in the autonomous area and S4 meaning complete recovery (2-point discrimination, 2-6 mm).	Assessed at 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Meaningful recovery (MR) of motor and sensory function	Medical Research Council Classification (MRCC) of motor recovery score. Meaningful recovery is defined as ≥ M3 MRCC of motor recovery and ≥ S3 MRCC of sensory recovery.	Assessed at Week 4, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24
Treatment response (TR) of motor and sensory function	Medical Research Council Classification (MRCC) of motor recovery score. Treatment response is defined as a 1-point increase in MRCC score from post-operative baseline.	Assessed at Week 4, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24
Time to MR of motor and sensory function	Time from surgery to meaningful recovery of motor function in all repairs and of sensory function in mixed nerve repairs.	Assessed at Week 4, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24
Time to TR of motor and sensory function	Time from surgery to treatment response of motor function in all repairs and of sensory function in mixed nerve repairs.	Assessed at Week 4, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24
QuickDASH upper extremity disability score	The QuickDASH questionnaire (including Work and Sports/Performance Art modules if applicable) is a PROM questionnaire to measure physical functions and symptoms in participants with upper limb musculoskeletal disorders and will be used to assess the study participant's functional quality of life (QoL)as it pertains to the affected arm. This 11-item questionnaire addresses arm-specific symptoms and disability during the preceding week and is used to estimate the participant's view of disability. Each item is based on an ordinal scale from 1 to 5, where higher values are worse. QuickDASH scores range from 0 to 100, with a score of 0 indicating no disability and a score of 100 representing the most severe disability.	Assessed at 24 months
Lower Extremity Functional Scale (LEFS) score	The LEFS is a valid and reliable assessment for documenting function for individuals and groups with injury or disability to the lower extremity. It is based on the World Health Organization's model of disability and handicap and is applicable to a wide variety of participants with lower extremity orthopedic conditions, including participants with a range of disability levels, conditions, diseases, treatments, and ages. Applicable to sural nerve autograft group only. The LEFS consists of 20 questions, with each activity rated from 0 (extremely difficult or unable) to 4 (no difficulty). Scores range from 0 to 80, where higher scores indicate better lower limb function.	Assessed at 24 months

Collaborators and Investigators

• Sponsor: Axogen Corporation
• Investigators: Principal Investigator: R. Glenn Gaston, MD, OrthoCarolina Research Institute, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 12, 2026
• Primary Completion (Estimated): December 5, 2030
• Study Completion (Estimated): December 5, 2030

Study Registration Dates

• First Submitted: June 15, 2026
• First Submitted That Met QC Criteria: June 15, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: MRCC; Nerve Gap; Avance Nerve Graft; Sural Nerve Autograft; Processed Nerve Allograft; Peripheral Nerve Reconstruction; Mixed Nerve Repair; Motor Nerve Repair; Nerve-RESTORE
• Additional Relevant MeSH Terms: Nervous System Diseases; Wounds and Injuries; Neuromuscular Diseases; Peripheral Nervous System Diseases; Trauma, Nervous System; Peripheral Nerve Injuries
• Other Study ID Numbers: ANG-CP-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No