Charcot-Marie-Tooth Neuropathy Type 1APhase 1/2NCT03520751
Phase I/IIa Trial of scAAV1.tMCK.NTF3 for Treatment of CMT1A
A Phase 1/2 study testing scAAV1.tMCK.NTF3 in people with Charcot-Marie-Tooth Neuropathy Type 1A, run by Nationwide Children's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Charcot-Marie-Tooth Neuropathy Type 1A
- What is being tested?
- scAAV1.tMCK.NTF3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2027to Apr 2030
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Nationwide Children's Hospital
Columbus, Ohio, 43205
About this study
Official title: Phase I/IIa Trial Evaluating scAAV1.tMCK.NTF3 for Treatment of Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A)
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.
Read the detailed description
This clinical trial is an open-label, one-time injection study in which scAAV1.tMCK.NTF3 will be administered by intramuscular injections into the medial and lateral heads of gastrocnemius, tibialis anterior, and rectus femoris muscles in both legs in CMT1A subjects with PMP22 gene duplication. Three CMT1A patients, 18 to 35 years of age will be enrolled into one cohort in this trial. These adult subjects will be enrolled at an effective dose (8.87e11 vg/kg) based on a qPCR titer using linearized standards, equivalent to 4.00x1012 vg/kg based on a qPCR titer using supercoiled standards) distributed bilaterally between both limbs in Cohort 1. Post-gene transfer monitoring will include follow up visits on days 7, 14, 30, 60, 90, 120, and months 6, 9, 12, 15, 18 and 24 following gene transfer. Safety is the primary endpoint for this clinical gene transfer trial. Stopping criteria are based on development of unacceptable toxicity defined as the occurrence of any one Grade III or higher, unanticipated, treatment-related toxicity. The secondary endpoint is efficacy defined as halting of the decline in functional and sensory abilities measured by the CMT Pediatric Scale (CMTPedS) at 2 years post gene transfer. The CMTPedS is an 11-item scale comprised of the Functional Dexterity Test, Nine-Hole Peg Test (9HPT), hand grip, foot plantar flexion, foot dorsiflexion, pinprick sensation, vibration sensation, the Bruininks Oseretsky Test- Balance assessment, gait assessment, long jump, and six-minute walk test (6MWT). Exploratory outcome measures will include 10 meter run/walk timed test (10M), 100 meter timed test (100M), peroneal and ulnar CMAP amplitude and sensory and motor conduction velocities, a revised sensory testing to increase sensitivity for pinprick, touch-test and vibration assessments, visual analogue scales for pain and fatigue, Short Form Health Survey (SF-36) as Quality of Life measure, and circulating NT-3 levels.
- Conditions
- Charcot-Marie-Tooth Neuropathy Type 1A
- Being tested
- scAAV1.tMCK.NTF3
- Keywords
- CMT1A, scAAV1.tMCK.NTF3, NTF3
- Medical subject headings
- Charcot-Marie-Tooth Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
scAAV1.tMCK.NTF3Drug
Also called Neurotrophin Factor 3 (NTF3) vector
gene vector
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: scAAV1.tMCK.NTF3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety based on number of participants with adverse events.
AEs will be monitored and scored for severity and relatedness to the study article.
Measured: 2 years
Secondary outcomes (7)
Efficacy - the ability to halt the decline in functional and sensory abilities
CMT Pediatric Scale. Efficacy will be defined as the ability to halt the decline in functional and sensory abilities as measured by the CMTPedS at 2 years post gene transfer. This 11 item scale, developed by the Inherited Neuropathies Consortium, underwent validation testing in patients aged 3-20 years with CMT and generates a linear score of disability.
Measured: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
Physical Therapy Assessments The 100 Meter Timed Test (100m)
The 100 Meter Timed Test will be an exploratory outcome for this study.
Measured: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
Electrophysiological testing
Measurement of ulnar sensory nerve amplitude and compound muscle action potential (CMAP); amplitude of the ulnar nerve (recorded from the abductor digiti minimi muscle) and the peroneal nerve (recorded from the tibialis anterior muscle) and sensory and motor conduction velocities.
Measured: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
Sensory testing using semi-quantitative Rydel Seiffer tuning fork, Semmes-Weinstein Monofilaments and Neurotips
Perceptions of touch pressure, pricking pain and vibration will be graded on the index finger and the great toe as normal (0), decreased (1), or absent (2). In addition, the level of discrimination change for sensory modalities will be recorded in the dominant upper and lower limbs as normal (0), diminished or absent in fingers or toes (1), between fingers/toes and wrist or ankle (2), between wrist/ankle and mid-forearm or mid-calf level (3), between mid-forearm/mid-calf and elbow or knee (4) and above the level of elbow or knee (5).
Measured: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
Visual analog scale (VAS)
The visual analog scale (VAS) of pain intensity consists of a line, most often 100 mm long, with 2 descriptors representing extremes of pain intensity (e.g., no pain and extreme pain) at each end. Patients rate their pain intensity by making a mark somewhere on the line that represents their pain intensity and the VAS is scored by measuring the distance from the "no pain" end of the line.
Measured: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
Short Form Health Survey (SF-36)
The Short Form Health Survey (SF-36) will be used as a quality of life document to monitor and compare disease burden pre and post-treatment. The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index.
Measured: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
NT-3 levels
Circulating NT-3 levels will be measured by ELISA.
Measured: Screening, Day 7-2 yrs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2018
- Study startApr 2027 (estimated)
- Primary completionApr 2029 (estimated)
- Study completionApr 2030 (estimated)
Why it stopped: Study is withdrawing to the retirement of the PI.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Charcot-Marie-Tooth Neuropathy Type 1AStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zarife Sahenk, Nationwide Children's Hospital
- Investigators
- Zarife Sahenk, MD., PhD., Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03520751
- Sponsor's protocol ID
- IRB17-01287
- Status last verified
- Jul 2026
- First submitted
- 20 Apr 2018
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/IIa Trial Evaluating scAAV1.tMCK.NTF3 for Treatment of Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A)
- ClinicalTrials.gov ID
- NCT03520751
- Acronym / sponsor ID
- IRB17-01287
- Conditions
- Charcot-Marie-Tooth Neuropathy Type 1A
- Keywords
- CMT1A, scAAV1.tMCK.NTF3, NTF3
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study is withdrawing to the retirement of the PI.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Study start
- Apr 2027 (estimated)
- Primary completion
- Apr 2029 (estimated)
- Study completion
- Apr 2030 (estimated)
- First posted
- 11 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This clinical trial is an open-label, one-time injection study in which scAAV1.tMCK.NTF3 will be administered by intramuscular injections into the medial and lateral heads of gastrocnemius, tibialis anterior, and rectus femoris muscles in both legs in CMT1A subjects with PMP22 gene duplication. Three CMT1A patients, 18 to 35 years of age will be enrolled into one cohort in this trial. These adult subjects will be enrolled at an effective dose (8.87e11 vg/kg) based on a qPCR titer using linearized standards, equivalent to 4.00x1012 vg/kg based on a qPCR titer using supercoiled standards) distributed bilaterally between both limbs in Cohort 1. Post-gene transfer monitoring will include follow up visits on days 7, 14, 30, 60, 90, 120, and months 6, 9, 12, 15, 18 and 24 following gene transfer. Safety is the primary endpoint for this clinical gene transfer trial. Stopping criteria are based on development of unacceptable toxicity defined as the occurrence of any one Grade III or higher, unanticipated, treatment-related toxicity. The secondary endpoint is efficacy defined as halting of the decline in functional and sensory abilities measured by the CMT Pediatric Scale (CMTPedS) at 2 years post gene transfer. The CMTPedS is an 11-item scale comprised of the Functional Dexterity Test, Nine-Hole Peg Test (9HPT), hand grip, foot plantar flexion, foot dorsiflexion, pinprick sensation, vibration sensation, the Bruininks Oseretsky Test- Balance assessment, gait assessment, long jump, and six-minute walk test (6MWT). Exploratory outcome measures will include 10 meter run/walk timed test (10M), 100 meter timed test (100M), peroneal and ulnar CMAP amplitude and sensory and motor conduction velocities, a revised sensory testing to increase sensitivity for pinprick, touch-test and vibration assessments, visual analogue scales for pain and fatigue, Short Form Health Survey (SF-36) as Quality of Life measure, and circulating NT-3 levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose (8.87e11 vg/kg) | Experimental | Drug: scAAV1.tMCK.NTF3Three 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| scAAV1.tMCK.NTF3Also: Neurotrophin Factor 3 (NTF3) vectorgene vector | Drug | Dose (8.87e11 vg/kg) |
Primary outcome
Safety based on number of participants with adverse events.
Time frame: 2 years
AEs will be monitored and scored for severity and relatedness to the study article.
7 secondary outcomes
Efficacy - the ability to halt the decline in functional and sensory abilities
Time frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
Physical Therapy Assessments The 100 Meter Timed Test (100m)
Time frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
Electrophysiological testing
Time frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
Sensory testing using semi-quantitative Rydel Seiffer tuning fork, Semmes-Weinstein Monofilaments and Neurotips
Time frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
Visual analog scale (VAS)
Time frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
Short Form Health Survey (SF-36)
Time frame: Screening, Day 90, 6 months, 1yr, 18 months, 2 yrs
NT-3 levels
Time frame: Screening, Day 7-2 yrs
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zarife Sahenk, MD., PhD. principal investigator
Nationwide Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing scAAV1.tMCK.NTF3 in people with Charcot-Marie-Tooth Neuropathy Type 1A, run by Nationwide Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety based on number of participants with adverse events. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2026.