NMD670 for Charcot-Marie-Tooth Disease

(SYNAPSE-CMT Trial)

No longer recruiting at 19 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NMD670 for individuals with Charcot-Marie-Tooth (CMT) disease, types 1 and 2. It aims to assess the safety and effectiveness of NMD670 compared to a placebo, which contains no active medicine. The trial lasts 21 days, with participants taking the treatment twice daily. Eligible participants must be adults diagnosed with CMT type 1 or 2 through genetic tests and able to walk independently. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that NMD670 is likely to be safe for humans?

Research has shown that NMD670 has been safe and well-tolerated in past studies. In one study with healthy volunteers, no major safety issues arose with NMD670, suggesting the treatment is likely safe for people. These findings enhance understanding of its safety in humans. For those considering joining a trial with NMD670, this information may provide reassurance about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Charcot-Marie-Tooth disease?

Unlike the standard treatments for Charcot-Marie-Tooth disease, which often focus on managing symptoms like pain and muscle weakness, NMD670 offers a novel approach. Researchers are excited about NMD670 because it targets the underlying mechanisms of nerve degeneration, potentially slowing or even halting disease progression rather than just alleviating symptoms. This new mechanism of action could provide a significant breakthrough, offering hope for improved quality of life and better long-term outcomes for patients.

What evidence suggests that NMD670 might be an effective treatment for Charcot-Marie-Tooth disease?

Research shows that NMD670, which participants in this trial may receive, targets the connection between nerves and muscles, crucial for muscle movement. In earlier studies, NMD670 improved this connection in individuals with neuromuscular diseases like myasthenia gravis. This suggests it might also enhance muscle function in Charcot-Marie-Tooth (CMT) disease, a similar condition. The FDA has recognized NMD670's potential by granting it orphan drug status for treating CMT. These findings offer hope that NMD670 could benefit people with CMT. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06482437?cond=Roussy-levy%20syndrome%20OR%20%22hereditary%20areflexic%20dystasia,%20Roussy-levy%20type%22%20OR%20%22%20hereditary%20areflexic%20dystasia,%20Roussy-L%C3%A9vy%20type%22%20OR%20%22%20Roussy%20levy%20syndrome%22%20OR%20%22%20Roussy%20L%C3%A9vy%20Syndrome%22%20OR%20%22%20Roussy-levy%20disease%22%20OR%20%22%20Roussy-L%C3%A9vy%20syndrome%22&aggFilters=status:not%20rec&viewType=Table&rank=7

Safety and Efficacy of NMD670 in Adult Patients With Type ... 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 ...

2. nmdpharma.com nmdpharma.com/news/nmd-pharma-initiates-phase-2-study-of-nmd670-in-patients-with-cmt-type-1-and-2

NMD Pharma Initiates Phase 2 Study of NMD670 in ... NMD670 has demonstrated promising clinical results in a proof-of-mechanism study in patients with NMJ dysfunction in the rare neuromuscular disease myasthenia ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06482437

NCT06482437 | Safety and Efficacy of NMD670 in Adult ... 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 ...

4. nmdpharma.com nmdpharma.com/news/nmd-pharma-publishes-paper-in-annals-of-clinical-and-translational-neurology

NMD Pharma publishes new data on the role of ClC-1 ... Targeting the neuromuscular junction (NMJ) with ClC-1 inhibitors, such as NMD670, could enhance muscle function in patients with CMT, a rare neuromuscular ...

5. nmdpharma.com nmdpharma.com/news/fda-orphan-drug-designation

NMD Pharma Announces FDA Orphan Drug Designation ... NMD670 has been granted orphan-drug designation by the U.S. FDA for treatment of gMG and CMT. About Charcot-Marie-Tooth disease (CMT) CMT ...

6. synapse.patsnap.com synapse.patsnap.com/drug/2894d601a90349139221ae6f65c7edf7

Bromophenoxyazole Propanoic Acid - Drug Targets, ... A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of NMD670 over 21 days in Ambulatory Adult ...

7. nmdpharma.com nmdpharma.com/news/nmd-pharma-announces-publication-of-phase-1-clinical-trial-data-evaluating-nmd670-in-healthy-volunteers-in-the-journal-clinical-pharmacology-therapeutics

NMD Pharma Announces Publication of Phase 1 Clinical ... NMD670 was generally safe and well-tolerated in healthy subjects ... NMD670 for the Treatment of Patients with Charcot-Marie-Tooth Disease.