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.
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
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.
Single group
ELP-02
GeneticELP-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.
Incidence of Grade 3 or Higher Unanticipated Treatment-Related Adverse Events
Incidence and severity of unanticipated treatment-related adverse events graded as Grade 3 or higher will be assessed based on the occurrence of serious adverse events (SAEs) and adverse events (AEs), classified according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Improvement or stabilization of muscle fat fraction (MFF) by MRI
Improvement or stabilization of muscle fat fraction (MFF) by MRI of bilateral thigh and calf muscle evaluation
Improvement or stabilization in functional ability as measured by Charcot-Marie-Tooth Pediatric Scale (CMTPedS) score
Improvement or stabilization in functional abilities as measured by the total or subcomponents of the CMTPedS scale. Total scores range from 0 to 44, where lower scores indicate better functional ability.
Improvement or stabilization in functional ability as measured by CMT Functional Outcome Measure (CMTFOM) score
Improvement or stabilization in functional abilities as measured by the CMTFOM Scale. Total scores range from 0 to 100, where lower scores indicate better functional performance.
Improvement or stabilization in functional ability as measured by Timed Up and Go (TUG) Score
Improvement or stabilization in functional abilities as measured by the Timed Up and Go (TUG). Performance is measured as the time required to complete the TUG test, reported in seconds, with shorter completion times indicating better functional mobility.
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