Phase I/IIa Trial of scAAV1.tMCK.NTF3 for Treatment of CMT1A

NCT03520751 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB17-01287
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is an open-label one-time injection dose study in which scAAV1.tMCK.NTF3 will be administered by intramuscular injections into muscles in both legs in CMT1A subjects with PMP22 gene duplication. Three subjects ages 18 to 35 years receiving (8.87e11 vg/kg) will be enrolled.

Conditions

Charcot-Marie-Tooth Neuropathy Type 1A

Keywords

CMT1A; scAAV1.tMCK.NTF3; NTF3

Outcome Measures

Primary Outcomes (1)

• Safety based on number of participants with adverse events.

  AEs will be monitored and scored for severity and relatedness to the study article.

  2 years

Secondary Outcomes (7)

• Efficacy - the ability to halt the decline in functional and sensory abilities

  Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs

• Physical Therapy Assessments The 100 Meter Timed Test (100m)

  Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs

• Electrophysiological testing

  Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs

• Sensory testing using semi-quantitative Rydel Seiffer tuning fork, Semmes-Weinstein Monofilaments and Neurotips

  Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs

• Visual analog scale (VAS)

  Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs

Study Arms (1)

Dose (8.87e11 vg/kg)

EXPERIMENTAL

Three patients age 18-35 will receive intramuscular injection of recombinant AAV1 carrying a human NFT3 gene under the control of the tMCK promoter (scAAV1.tMCK.NTF3) distributed bilaterally between both limbs at a dose of 8.87e11 vg/kg.

Drug: scAAV1.tMCK.NTF3

Interventions

scAAV1.tMCK.NTF3 DRUG

gene vector

Also known as: Neurotrophin Factor 3 (NTF3) vector

Dose (8.87e11 vg/kg)

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects 18- 35 years old inclusive with CMT1A will be enrolled
• Must exhibit a 1.5 Mb duplication at 17p11.2 inclusive of the peripheral myelin protein 22 (PMP22) gene
• Males and females of any ethnic or racial group
• Must exhibit weakness of the ankle dorsiflexion muscle (but has full ROM against gravity and is able to stand on heels 3 seconds or greater)
• Abnormal nerve conduction velocities
• Ability to cooperate for clinical evaluation and repeat nerve conduction studies
• Willingness of sexually active subjects to practice a reliable method of contraception during the study

You may not qualify if:

• Active viral infection based on clinical observations or serological evidence of HIV, or Hepatitis B or C infection, herpesvirus or adenovirus
• Ongoing immunosuppressive therapy or immunosuppressive therapy within 6 months of starting the trial (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin)
• Persistent leukopenia or leukocytosis (WBC ≤ 3.5 K/µL or ≥ 20.0 K/µL) or an absolute neutrophil count \< 1.5K/µL
• Subjects with AAV1 binding antibody titers ≥ 1:50 as determined by ELISA immunoassay
• Subjects with circulating anti-NT-3 titers ≥ 1:50 as determined by ELISA immunoassay
• Treat with any investigational medication within 30 days before the infusion of study drug
• Abnormal laboratory values considered clinically significant (GGT \> 3XULN, bilirubin ≥ 3.0 mg/dL, creatinine ≥ 1.8 mg/dL, Hgb \< 8 or \> 18 g/Dl; WBC \> 15,000 per cmm)
• Any medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's wellbeing, safety, or clinical interpretability
• Ankle contractures or surgeries preventing proper muscle strength testing
• Pregnancy or lactation (females subjects will be tested for pregnancy)
• Limb surgery in the past six months
• Severe infection (e.g. pneumonia, pyelonephritis, or meningitis) within 4 weeks before gene transfer visit (enrollment may be postponed)
• Anyone unwilling to disclose study participation with primary care physician and other medical providers.
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease

Interventions

Disease Vectors

Condition Hierarchy (Ancestors)

Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Disease Transmission, Infectious; Public Health; Environment and Public Health; Chain of Infection; Epidemiologic Methods

Study Officials

• Zarife Sahenk, MD., PhD.

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dawn Scott

CONTACT

(614)722-2715; dawn.scott@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: May 11, 2018
• Study Start (Estimated): April 1, 2027
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2030
• Last Updated: June 24, 2025

Record last verified: 2025-06

Locations

US (1)