A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J) (CMT4J)

• ClinicalTrials.gov Identifier: NCT03810508
• Recruitment Status: Terminated
• First Posted: January 18, 2019
• Last Update Posted: March 31, 2022
• Sponsor: Neurogene Inc.
• Information provided by (Responsible Party): Neurogene Inc.

Study Description

Brief Summary:

Charcot-Marie-Tooth 4J (CMT4J) is a rare inherited peripheral neuropathy often characterized by rapidly progressive, asymmetrical upper and lower extremity weakness, muscle atrophy leading to loss of ambulation, respiratory compromise and premature death with no available treatment.

The purpose of this study is to investigate the clinical characteristics and natural clinical progression of symptoms in individuals with CMT4J. This natural history study is important to better understand disease course to be able to determine clinically meaningful outcome measures for use in future clinical trials.

Condition or disease
Charcot-Marie-Tooth Disease; Hereditary Motor and Sensory Neuropathy IV

Detailed Description:

Charcot-Marie-Tooth (CMT) diseases are the most common inherited motor and sensory neuropathies, composed of a group of pathologically and genetically distinct subtypes ranging from slowly to rapidly progressive disease.

CMT4J is a rare subtype of CMT caused by mutations in the FIG4 gene. Pediatric-onset disease can often be characterized by rapid progression of muscle weakness and atrophy, culminating in loss of ambulation and respiratory compromise and premature death. Adult-onset CMT4J can present with a more variable disease course.

No prospective natural history study for CMT4J has been reported. This study aims to prospectively investigate the natural history of CMT4J, and concurrently to identify potential outcome measures that could be used in future clinical trials. No investigational product will be provided in the study.

Study Design

• Study Type: Observational
• Actual Enrollment: 21 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J)
• Actual Study Start Date: July 18, 2019
• Actual Primary Completion Date: February 15, 2022
• Actual Study Completion Date: February 15, 2022

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Charcot Marie-Tooth Pediatric Scale (CMTPedS) [ Time Frame: Change is being assessed from baseline measures every 6 months for up to five years ]
   This an 11 item scale is used in patients younger than 18 yrs of age and generates a linear score of disability.
2. Charcot-Marie-Tooth Neuropathy Score second version (CMTNSv2) [ Time Frame: Change is being assessed from baseline measures every 6 months for up to five years ]
   This is a 36 point scale that monitors disease impairment and progression with a higher score signifies increased disability.
3. Charcot Marie-Tooth Functional Outcome Measure (CMT-FOM) [ Time Frame: Change is being assessed from baseline measures every 6 months for up to five years ]
   This is a performance-based outcome assessment which measures limitations in functional abilities in adults.
4. CMT Health Index (CMTHI) [ Time Frame: Change is being assessed from baseline measures every 6 months for up to five years ]
   The CMTHI is a disease-specific, adult patient reported outcome measure designed to capture the disease burden of inherited neuropathies in the context of a clinical trial.
5. Magnetic Resonance Imaging (MRI) of the calf muscles without contrast [ Time Frame: Change is being assessed from baseline measures every 6 months for up to five years ]
   MRI of bilateral thigh and calf muscles will be performed to characterize the pattern of muscle involvement and evaluate the muscle fat fraction (MFF).
6. Nerve Conduction Study (NCS) [ Time Frame: Change is being assessed from baseline measures every 6 months for up to five years ]
   NCS is an electrophysiological test to evaluate the sensory and motor responses in the upper and lower extremities.
7. Pulmonary Function Test, sitting and lying (PFT) [ Time Frame: Change is being assessed from baseline measures every 12 months for up to five years ]
   The purpose of the PFT is to identify the severity and progression of pulmonary impairment, and will be performed every 12 months.

Biospecimen Retention:   Samples With DNA

Patients will also have the opportunity to have biospecimens stored for up to 10 years for future exploratory analyses.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of CMT4J based on clinical presentation and genetic testing (known or suspected pathogenic mutation in FIG4).

Criteria

Subjects must have a prior confirmed molecular (genetic) diagnosis of CMT4J by clinical presentation and genetic testing.

Contacts and Locations

Locations

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Texas

University of Texas Southwestern

Dallas, Texas, United States, 75390

Sponsors and Collaborators

Neurogene Inc.

Investigators

• Study Director: Elise Beausoleil; Neurogene Inc.

More Information

• Responsible Party: Neurogene Inc.
• ClinicalTrials.gov Identifier: NCT03810508
• Other Study ID Numbers: CMT4J-100
• First Posted: January 18, 2019
• Last Update Posted: March 31, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Neurogene Inc.:

CMT4J

Additional relevant MeSH terms:

Tooth Diseases; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy; Refsum Disease; Stomatognathic Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases