Treatment of Charcot-Marie-Tooth Disease, Axonal, Type 2S (CMT2S) in an Individual Patient

NCT07223632 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: VP-VCA-894A-2101
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is an 'N of 1', open-label, single center study to evaluate the safety of therapy with VCA-894A, an ASO designed to rescue and restore the activity of IGHMBP2, when administered by intrathecal injection.

Conditions

Charcot Marie Tooth Disease (CMT); Neuromuscular Diseases (NMD)

Outcome Measures

Primary Outcomes (3)

• Assessment of safety of therapy with VCA-894A when administered via intrathecal injection, as measured by the incidence of adverse events.

  Safety will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with VCA-894A.

  295 days

• Assessment of CMT2S symptoms following chronic administration of intrathecal VCA-894A, as determined by the change in the Revised Upper Limb Module for Spinal Muscular Atrophy (RULM).

  The Revised Upper Limb Module for Spinal Muscular Atrophy (RULM) scores range from a minimum of 0 to a maximum of 37 points, with higher scores indicating better upper limb function.

  295 days

• Assessment of CMT2S symptoms following chronic administration of intrathecal VCA-894A, as determined by the change in the Hammersmith Functional Motor Scale - Expanded (HFMSE).

  The Hammersmith Functional Motor Scale - Expanded (HFMSE) scores range from a minimum of 0 to a maximum of 66 points, with higher scores indicating greater motor functioning.

  295 days

Secondary Outcomes (1)

• Rescue of IGHMBP2, as determined by the change in IGHMBP2 mRNA expression from baseline.

  295 days

Study Arms (1)

VCA-894A

EXPERIMENTAL

Drug: VCA-894A

Interventions

VCA-894A DRUG

intrathecal antisense oligonucleotide injection

VCA-894A

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability and acceptance to provide written informed consent.
• Genetically confirmed diagnosis of CMT2S with confirmed IGHMBP2 intronic cryptic splice variant c. 1235+894C\>A.

You may not qualify if:

• Significant clinical deterioration of the patient's neurologic status, as judged by the Investigator.
• Non-reversible conditions that are contraindications to lumbar puncture.
• Pregnancy, recent pregnancy (within 6 weeks), or women who are breastfeeding.

Sponsors & Collaborators

• Vanda Pharmaceuticals: lead

Study Sites (1)

Vanda Investigational Site

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Smieszek S, Przychodzen B, Tyner C, Johnson C, Bai H, Kwon JM, Hagan DW, Niccum C, Brighton R, Hawkins K, Aiken R, Nawaz A, Guo X, Hickman J, Polymeropoulos CM, Birznieks G, Polymeropoulos MH. Potential ASO-based personalized treatment for Charcot-Marie-Tooth disease type 2S. Mol Ther Nucleic Acids. 2025 Feb 4;36(1):102479. doi: 10.1016/j.omtn.2025.102479. eCollection 2025 Mar 11.

  PMID: 40060931 BACKGROUND

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease; Neuromuscular Diseases

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; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2025
• First Posted: November 3, 2025
• Study Start: May 13, 2025
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: November 3, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)