Safety and Efficacy of NMD670 in Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease (SYNAPSE-CMT)

A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of NMD670 Over 21 Days in Ambulatory Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease

This Phase 2a study aims to evaluate the efficacy, safety and tolerability of NMD670 vs placebo administered twice a day (BID) for 21 days in ambulatory adult patients with Charcot-Marie-Tooth disease type 1 and type 2.

Study Overview

• Status: Completed
• Conditions: Charcot-Marie-Tooth Disease
• Intervention / Treatment: Drug: NMD670; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University Hospitals Leuven, Department of Neurology
  • Liège, Belgium, 4000
    • CHR de la Citadelle- Site Citadelle Neurolgie Boulevard du 12eme de Ligne 1
• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital
  • Copenhagen, Denmark
    • Rigshospitalet, Department of Neurology
• France
  • Marseille, France, 13005
    • CHU Marseille, Reference centre for neuromuscular diseases and ALS Department of Neuromuscular Diseases
  • Nantes, France
    • Laboratoire d'Explorations Fonctionnelles, CHU Nantes
  • Nice, France, 06001
    • Centre Hospitalier Universitaire de Nice
  • Paris, France, 75651
    • Institut de Myologie Groupe Hospitalier Pitié-Salpêtrière
  • Paris, France, 94275
    • Bicetre University Hospital
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center, Department of Neurology
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Mass General Neurology
  • Missouri
    • Columbia, Missouri, United States, 65211
      • NextGen Precision Health
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Neuromuscular Disease Center
  • Ohio
    • Columbus, Ohio, United States, 43221
      • OSU Department of Neurology Division of Neuromuscular Diseases
  • Texas
    • Austin, Texas, United States, 78759
      • National Neuromuscular research Institute, PLLC
  • Washington
    • Spokane, Washington, United States, 99204
      • Providence Medical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female participants must be 18 to 70 years inclusive at the time of signing the ICF.
• Diagnosis of CMT type 1 or 2 confirmed by genetic testing.
• Body mass index between 18 and 35 kg/m2, inclusive, at screening, and with a minimum weight of 40 kg
• Contraceptive use by men and women must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Participant is capable of and has given signed informed consent

Exclusion Criteria:

• Participants with other significant disease that may interfere with the interpretation of study data (e.g., other neuromuscular diseases) and/or ability to complete the tests, in the opinion of the Investigator.
• Participants with laboratory test result abnormalities at screening considered clinically significant by the Investigator.
• Participants who have received treatment with another IMP within 30 days (or 5 half-lives of the medication, whichever is longer) prior to day 1.
• Participants with history of poor compliance with relevant therapy in the opinion of the Investigator.
• Female participants who plan to become pregnant during the study or are currently pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Tablets taken twice daily for 21 days
Experimental: NMD670	Drug: NMD670; Tablets taken twice daily for 21 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline to day 21 in 6-minute walk test total distance for NMD670 vs placebo	Baseline to day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment emergent adverse events	Summarised per treatment	Over 21 days of dosing
Incidence of serious treatment emergent adverse events	Summarised per treatment	Over 21 days of dosing
Incidence of clinically significant abnormalities on physical examinations	Summarised per treatment	Over 21 days of dosing
Incidence of clinically significant abnormalities on safety laboratory parameters	Summarised per treatment	Over 21 days of dosing
Incidence of clinically significant vital signs abnormalities	Summarised per treatment	Over 21 days of dosing
Incidence of clinically significant ECG abnormalities	Summarised per treatment	Over 21 days of dosing
Incidence of Suicidal Ideation or Suicidal Behavior	Summarised per treatment	Over 21 days of dosing
Change from baseline to day 21 in CMT Functional Outcome Measure Total Score and Individual Items for NMD670 vs placebo	CMT Functional Outcome Meausre is a 12-item scale. Scale goes from 0-100 and a higher score indicates worse symptomatology	Baseline to day 21
Change from baseline to day 21 in 6-minute walk test fatigue index for NMD670 vs placebo		Baseline to day 21
Change from baseline to day 21 in Overall Neuropathy Limitation Scale total score and individual items for NMD670 vs placebo	The Overall Neuropathy Limitation Scale consists of an arm and a leg scale. Scale goes from 0-12 and a higher score indicates worse symptomatology	Baseline to day 21
Change from baseline to day 21 in CMT Health Index total score and individual domains for NMD670 vs placebo	The CMT Health Index has 18 domains. Scale goes from 0-100 and a higher score indicates worse symptomatology	Baseline to day 21
Change from baseline to day 21 in SF-36 total score and individual domains for NMD670 vs placebo	The SF-36 has 8 domains. Scale goes from 0-100 and a lower score indicates worse symptomatology	Baseline to day 21
Incidence of clinically significant abnormalities on opthalmological examinations	Summarised per treatment	From screening (day -28 to day -1) until follow up (day 28)]
Change from baseline to day 21 in the time to complete the 10MW/RT for NMD670 vs placebo		Baseline to day 21
Change from baseline to day 21 in jitter and blocking for NMD670 vs placebo		Baseline to day 21
Proportion of participants with clinically meaningful change from baseline in CMT-FOM total score and individual items for NMD670 vs placebo		Baseline to day 21
Proportion of participants with clinically meaningful change from baseline in 10MW/RT for NMD670 vs placebo		Baseline to day 21
Proportion of participants with clinically meaningful change from baseline in ONLS total score for NMD670 vs placebo		Baseline to day 21
Proportion of participants with clinically meaningful change from baseline in CMT-HI total score and individual domains for NMD670 vs placebo		Baseline to day 21
Proportion of participants with clinically meaningful change from baseline in SF-36 total score and individual domains for NMD670 vs placebo		Baseline to day 21

Collaborators and Investigators

• Sponsor: NMD Pharma A/S

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2024
• Primary Completion (Actual): October 28, 2025
• Study Completion (Actual): November 4, 2025

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): November 12, 2025
• Last Update Submitted That Met QC Criteria: November 11, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Hereditary Sensory and Motor Neuropathy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Charcot-Marie-Tooth Disease; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: NMD670-02-0003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No