NMD670 for Charcot-Marie-Tooth Disease

(SYNAPSE-CMT Trial)

Recruiting at 17 trial locations

Overseen By [e-mail]

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NMD Pharma A/S

Disqualifiers: Other neuromuscular diseases, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 3 weeks

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have taken another investigational medication recently, you may need to wait 30 days before joining this study.

What data supports the effectiveness of the drug NMD670 for Charcot-Marie-Tooth Disease?

There is no direct data on NMD670, but a similar drug combination, PXT3003, has shown promise in treating Charcot-Marie-Tooth disease type 1A by improving nerve function and muscle strength in animal models and early human trials. ^{1 2 3 4 5}

How is the drug NMD670 different from other treatments for Charcot-Marie-Tooth Disease?

NMD670 is a novel treatment for Charcot-Marie-Tooth Disease, which currently has no cure and only symptomatic treatments available. Unlike other treatments, NMD670 may offer a new approach, but specific details about its mechanism or benefits compared to existing options are not provided in the available research. ^{4 6 7 8 9}

What is the purpose of this trial?

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.

Eligibility Criteria

Adults aged 18-70 with Charcot-Marie-Tooth disease types 1 or 2, confirmed by genetic testing. Participants must have a BMI of 18-35 and weigh at least 40 kg. They should be able to consent to the study and follow local contraceptive guidelines.

Inclusion Criteria

My BMI is between 18 and 35, and I weigh at least 40 kg.

I have signed a consent form to participate.

I am following local guidelines for contraception while in this study.

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 with history of poor compliance with relevant therapy in the opinion of the Investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive NMD670 or placebo twice a day for 21 days

3 weeks

Daily dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• NMD670

Trial Overview The trial is testing NMD670 against a placebo in adults with Charcot-Marie-Tooth disease. It's given twice daily for three weeks to see if it's safe, tolerable, and effective in improving the condition.

Participant Groups

Group I: NMD670 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

NMD670 is already approved in United States for the following indications:

Approved in United States as NMD670 for:

• Generalized Myasthenia Gravis (gMG)
• Charcot-Marie-Tooth disease (CMT)

Who Is Running the Clinical Trial?

NMD Pharma A/S

Lead Sponsor

Trials

6

Recruited

290+

Findings from Research

A combination therapy called PXT3003, consisting of (RS)-baclofen, naltrexone hydrochloride, and D-sorbitol, showed promising results in improving myelination and reducing PMP22 expression in preclinical models of Charcot-Marie-Tooth disease type 1A (CMT1A), which affects peripheral nerve function.

In tests on CMT1A transgenic rats and mice recovering from nerve injuries, PXT3003 enhanced nerve conduction, improved myelination of small fibers, and supported axonal regeneration, suggesting it could be a viable treatment option for this currently untreatable condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polytherapy with a combination of three repurposed drugs (PXT3003) down-regulates Pmp22 over-expression and improves myelination, axonal and functional parameters in models of CMT1A neuropathy. Chumakov, I., Milet, A., Cholet, N., et al.[2018]

PXT3003, a combination of baclofen, naltrexone, and sorbitol, was shown to improve motor and sensory functions in a study of adult male CMT1A rats over 3 months, outperforming its individual components and dual combinations.

The treatment appeared to enhance neuromuscular junction (NMJ) function and muscle innervation, leading to better motor performance, despite only a slight increase in myelinated axons, suggesting that PXT3003's benefits may be independent of myelination improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic PXT3003 therapy uncouples neuromuscular function from dysmyelination in male Charcot-Marie-Tooth disease type 1A (CMT1A) rats. Prukop, T., Wernick, S., Boussicault, L., et al.[2021]

In a study of 56 patients with Charcot-Marie-Tooth disease, 91.7% reported that medical cannabis provided at least 50% pain relief, with many experiencing an 80% reduction in pain.

The majority of respondents (80%) reported using fewer opiates and other medications, indicating that cannabis may be an effective alternative for pain management in this population, despite some experiencing mild side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Reported Outcomes Using Medical Cannabis for Managing Pain in Charcot-Marie-Tooth Disease. Canals, PC., Aguilar, AG., Carter, GT., et al.[2023]

In a phase 3 trial involving 323 subjects with mild to moderate Charcot-Marie-Tooth disease type 1A, high-dose PXT3003 showed a significant improvement in the Overall Neuropathy Limitations Scale compared to placebo, indicating its potential efficacy as a treatment.

Both doses of PXT3003 were found to be safe and well-tolerated, suggesting that this medication could be a promising option for managing symptoms of CMT1A, despite the high-dose group experiencing some issues with formulation stability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot-Marie-Tooth type 1A. Attarian, S., Young, P., Brannagan, TH., et al.[2023]

PXT3003, a combination of three approved compounds, was found to be safe and well-tolerated in a study of 80 adults with mild-to-moderate Charcot-Marie-Tooth type 1A disease over one year.

The highest dose of PXT3003 showed significant improvements in clinical measures of neuropathy, with an 8% improvement in the Charcot-Marie-Tooth Neuropathy Score and a 12.1% improvement in the Overall Neuropathy Limitations Scale, suggesting potential efficacy for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol (PXT3003) in patients with Charcot-Marie-Tooth disease type 1A. Attarian, S., Vallat, JM., Magy, L., et al.[2018]

A 5-week rehabilitation program using ankle exercises and Kinect videogame activities showed improvements in balance and endurance in a 9-year-old boy with CMT1A, although ankle strength did not increase.

The positive outcomes for balance and endurance suggest that videogame-directed physical activities could be a promising area for further research in improving function in children with CMT1A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensive strength and balance training with the Kinect console (Xbox 360) in a patient with CMT1A. Pagliano, E., Foscan, M., Marchi, A., et al.[2018]

A patient with Charcot Marie Tooth disease caused by an MPZ mutation (p.Ser63del) exhibited symptoms resembling chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), including recurrent quadriparesis and cranial nerve involvement.

The patient showed a positive response to treatment with prednisone and cyclophosphamide, highlighting that immune-mediated complications can occur in CMT due to MPZ mutations, suggesting a link between defective myelin proteins and increased vulnerability to immune attacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-mediated inflammatory polyneuropathy overlapping Charcot-Marie-Tooth 1B. Escorcio-Bezerra, ML., Pinto, WBVR., Bichuetti, DB., et al.[2020]

In a study of 101 patients with Charcot-Marie-Tooth Disease type 1A (CMT1A), higher body mass index (BMI) did not impact nerve conduction studies but was correlated with clinical symptoms like loss of sensation and motor strength in the lower extremities.

The relationship between BMI and clinical symptoms is unclear; it is uncertain whether the loss of motor strength and sensation leads to a higher BMI or if a higher BMI contributes to these clinical signs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Charcot-Marie-Tooth Disease Type 1A: Influence of Body Mass Index on Nerve Conduction Studies and on the Charcot-Marie-Tooth Examination Score. Jerath, NU., Shy, ME.[2018]

A missense mutation (Ser44Phe) in the MPZ gene was identified in a large Sardinian family with hereditary motor and sensory neuropathy type II (HMSN II), marking the first known instance of an MPZ mutation linked to this axonal form of Charcot-Marie-Tooth disease.

This discovery suggests that genetic testing for HMSN II should include the MPZ gene, which was previously not considered relevant for this type of neuropathy, potentially improving diagnosis and understanding of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Charcot-Marie-Tooth disease type 2 associated with mutation of the myelin protein zero gene. Marrosu, MG., Vaccargiu, S., Marrosu, G., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Polytherapy with a combination of three repurposed drugs (PXT3003) down-regulates Pmp22 over-expression and improves myelination, axonal and functional parameters in models of CMT1A neuropathy. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Synergistic PXT3003 therapy uncouples neuromuscular function from dysmyelination in male Charcot-Marie-Tooth disease type 1A (CMT1A) rats. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Patient Reported Outcomes Using Medical Cannabis for Managing Pain in Charcot-Marie-Tooth Disease. [2023]

4. England pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot-Marie-Tooth type 1A. [2023]

5. England pubmed.ncbi.nlm.nih.gov

An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol (PXT3003) in patients with Charcot-Marie-Tooth disease type 1A. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Intensive strength and balance training with the Kinect console (Xbox 360) in a patient with CMT1A. [2018]

7. Scotland pubmed.ncbi.nlm.nih.gov

Immune-mediated inflammatory polyneuropathy overlapping Charcot-Marie-Tooth 1B. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Charcot-Marie-Tooth Disease Type 1A: Influence of Body Mass Index on Nerve Conduction Studies and on the Charcot-Marie-Tooth Examination Score. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Charcot-Marie-Tooth disease type 2 associated with mutation of the myelin protein zero gene. [2019]