Study of Intrathecal ELP-02 for Charcot-Marie-Tooth Disease Type 4J (CMT4J)

A Phase 1/2 Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of a Single Dose of ELP-02 Delivered Via Lumbar Intrathecal Administration in Charcot-Marie-Tooth-4J (CMT4J)

First-in-human Phase 1/2, open-label study to evaluate the safety, tolerability, and efficacy of a single lumbar intrathecal dose of ELP-02 to individuals with CMT4J.

ELP-02 is an AAV9-based gene therapy vector that expresses the fully functional form of FIG4 under the control of a synthetic promoter. ELP-02 will be delivered intrathecally and is designed to achieve stable, potentially life-long expression of FIG4 in non-dividing cells. This clinical study is a first-in-human study designed to assess safety and tolerability of ELP-02 in individuals with CMT4J.

Inclusion Criteria:

• Male and females between the ages of 3 and 20 years at the time of screening.
• Molecularly-confirmed diagnosis of CMT4J (confirmed by a CLIA certified, CE-marked, or equivalent lab) due to bi-allelic pathogenic variants (by ACMG criteria) in the FIG4 gene where one of the mutations must be the pathogenic I41T variant, with the second mutation either being another pathogenic or likely pathogenic variant (by ACMG criteria).
• Clinical signs and symptoms consistent with CMT4J disease/motor symptoms
• No more than moderate severity of the disease as measured by a CMTPeds score of <35 or investigator's discretion
• Written informed consent provided by subject/parent/guardian and willingness to participate and comply with all the study related visits and procedures. Assent provided by children 10 to 17 years old based on their ability to understand the risks and possible benefits, and the activities expected of them.
• Subjects able to reproduce must use a barrier method of contraception for the first 12 months after dosing as well as at least one additional acceptable birth control method if sexually active
• Male subjects must agree not to donate sperm for the remainder of their lifetime after receiving ELP-02
• Female subjects must agree not to donate eggs for the remainder of their lifetime after receiving ELP-02

Exclusion Criteria:

• Prior or ongoing medical condition, medical history, physical findings, cardiovascular/ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
• Clinically significant abnormal laboratory values (hemoglobin < 6 or > 20 g/dL; white blood cell > 20,000 per cmm, platelets count < 100,000 per cmm; INR > ULN; GGT, ALT, and AST or total bilirubin > 2x ULN, creatinine ≥ 1.5 mg/dL) prior to gene replacement therapy.
• History of HbA1C > 6.0%
• Contraindication or unwillingness to undergo lumbar puncture.
• Presence of a concomitant medical condition that precludes use of anesthetics for sedated procedures.
• History of hypersensitivity to sirolimus, tacrolimus, corticosteroids, gadolinium, iodine or shellfish.
• Concomitant chronic drug treatment that would cause clinically significant interactions with immunosuppressive agents used in the study.
• The presence of significant CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
• Recent or planned elective surgical procedures that would confound the scientific rigor or interpretation of results of the study.
• Reason to believe that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
• Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study.
• Enrollment and participation in another interventional clinical trial 90 days before first visit.
• Diagnosis of a second neurodegenerative/peripheral neuropathy disease or another genetic syndrome with a progressive course.
• Advanced stage disease defined by the use of chronic invasive ventilatory support (tracheostomy with ventilator dependence) and a non-communicative status.
• Active viral infection (including HIV or serology positive for Hepatitis B or C, or COVID-19).
• Bacterial infection requiring antibiotics within the 6 weeks prior to infusion.
• Positive beta hCG pregnancy test (females of childbearing age will have pregnancy test at Screening and Day-1).