The Treatment of Charcot-Marie-Tooth Disease, Axonal, Type 2S (CMT2S) in an Individual Patient With Confirmed IGHMBP2 Intronic Cryptic Splice Variant C. 1235+894C>A That is Amenable to Antisense Oligonucleotide (ASO)-Mediated Correction of IGHMBP2 Splicing
| Registry | NCT07223632 |
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| Status | Active not recruiting |
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| Phase | Phase 1 / Phase 2 |
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| Study type | Interventional; na, single group, masking: none, treatment |
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| Enrollment | 1 (Actual) |
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| Sponsor | Vanda Pharmaceuticals (Industry) |
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| Conditions | Charcot Marie Tooth Disease (CMT), Neuromuscular Diseases (NMD) |
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| Interventions | VCA-894A (Drug) |
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| Dates | start 2025-05-13, primary completion 2027-03-01 (estimated), completion 2027-03-01 (estimated), first posted 2025-11-03, last updated 2026-08-19 |
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| Locations | 1 site in United States |
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-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.
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+Arms and interventions
| Arm | Type | Interventions | Description |
|---|
| VCA-894A | Experimental | Drug: VCA-894A | |
- VCA-894A (Drug): intrathecal antisense oligonucleotide injection
+Outcome measures
Primary outcomes
- Assessment of safety of therapy with VCA-894A when administered via intrathecal injection, as measured by the incidence of adverse events. [631 days]: Safety will be assessed by determining the incidence, severity, and dose relationship of adverse events that are related to treatment with VCA-894A.
- 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). [631 days]: 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.
- Assessment of CMT2S symptoms following chronic administration of intrathecal VCA-894A, as determined by the change in the Hammersmith Functional Motor Scale - Expanded (HFMSE). [631 days]: 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.
Secondary outcomes
- Rescue of IGHMBP2, as determined by the change in IGHMBP2 mRNA expression from baseline. [631 days]: IGHMBP2 mRNA, which is the target of VCA-894A therapy, will be measured in both the cerebrospinal fluid (CSF) and blood by qPCR relative expression.
+Eligibility
Sex: Female
Inclusion Criteria:
* Ability and acceptance to provide written informed consent.
* Genetically confirmed diagnosis of CMT2S with confirmed IGHMBP2 intronic cryptic splice variant c. 1235+894C>A.
Exclusion Criteria:
* 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.
+Locations (1)
| Facility | City | Country | Status |
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| Vanda Investigational Site | Madison, Wisconsin | United States | |
+Publications
- 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