NMD670 for Myasthenia Gravis

(SYNAPSE-MG Trial)

Recruiting at 42 trial locations

Overseen By NMD Pharma A/S

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NMD Pharma A/S

Disqualifiers: Pregnancy, Breastfeeding, Poor compliance, 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

84 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NMD670 to determine its effectiveness for people with myasthenia gravis (MG), a condition that causes muscle weakness. Researchers aim to assess the safety and efficacy of NMD670 by comparing three different doses to a placebo (a pill with no active ingredient). The trial targets adults with MG who have antibodies against AChR or MuSK, specific proteins involved in the disease. Those struggling with MG and testing positive for these antibodies may find this trial suitable. As a Phase 2 trial, the research focuses on measuring 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 whether you need to stop taking your current medications. However, if you have taken an investigational medical product recently, you may need to wait 30 days or more before joining the study.

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

Research has shown that NMD670 is generally safe for people. Studies have found it to be well-tolerated by both healthy individuals and those with myasthenia gravis, a condition causing muscle weakness. In earlier tests, muscle stiffness was the only side effect linked to the dose, occurring only at the highest doses. Overall, NMD670 has a good safety record, meaning most people don't experience serious issues when taking it. This makes it a promising choice for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Myasthenia Gravis?

NMD670 is unique because it targets myasthenia gravis differently from typical treatments like acetylcholinesterase inhibitors or immunosuppressants. Unlike these standard options, NMD670 works by modulating the immune system's response, potentially offering a more targeted approach to managing symptoms. Researchers are excited about its potential for fewer side effects and increased effectiveness, making it a promising option for patients who haven't found relief with current therapies.

What evidence suggests that NMD670 might be an effective treatment for Myasthenia Gravis?

Research has shown that NMD670 could be promising for people with myasthenia gravis (MG). In earlier studies, patients with MG experienced stronger muscles, as indicated by an improved Quantitative Myasthenia Gravis (QMG) score, which measures the severity of MG symptoms. NMD670 targets specific parts of muscle cells, boosting muscle strength and stamina. Initial findings also suggest that NMD670 is generally safe and well-tolerated. These results offer hope for people dealing with the challenging symptoms of MG. Participants in this trial will receive either a low, mid, or high dose of NMD670, or a placebo, to further evaluate its effectiveness and safety. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults aged 18-75 with Myasthenia Gravis (MG), specifically those who have muscle weakness and positive AChR or MuSK antibody tests. Participants must be able to swallow tablets, have a BMI of 18-35 kg/m2, weigh at least 40 kg, and use contraception in line with local guidelines.

Inclusion Criteria

My condition is moderate to severe myasthenia gravis.

I am using birth control as required by local laws for this study.

I have signed a consent form to participate.

Exclusion Criteria

I have had trouble following my myasthenia gravis treatment plan.

Participants with other significant clinical and/or laboratory safety findings that may interfere with the study

Participants who received treatment with an investigational medical product within 30 days prior to Day 1

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 the safety and effectiveness of three different doses of NMD670 compared to a placebo in treating MG. The medication or placebo is taken twice daily for three weeks by patients with antibodies against AChR or MuSK.

How Is the Trial Designed?

Group I: NMD670 mid dose Experimental Treatment 1 Intervention

Group II: NMD670 low dose Experimental Treatment 1 Intervention

Group III: NMD670 high dose Experimental Treatment 1 Intervention

Group IV: 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

The development of small molecule mGlu5 NAMs (negative allosteric modulators) for treating psychiatric and neurodegenerative disorders has progressed significantly, with several compounds currently in clinical trials for conditions like Fragile X Syndrome (FXS), Parkinson's Disease-L-Dopa Induced Dyskinesia (PD-LID), and Major Depressive Disorder (MDD).

Despite some recent clinical trial disappointments that have tempered enthusiasm, the field remains active, with new and diverse small molecules being developed, indicating ongoing potential for effective treatments targeting the mGlu5 receptor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mGlu5 negative allosteric modulators: a patent review (2013 - 2016). Emmitte, KA.[2017]

Negative allosteric modulators (NAMs) of the mGlu(5) receptor show promise as potential treatments for various central nervous system disorders, including anxiety, pain, and Parkinson's disease, supported by both preclinical and recent clinical data.

Recent advancements in the development of new mGlu(5) NAM chemotypes highlight the ongoing research and potential for these compounds to provide effective therapies, with discussions on their structure-activity relationships and synthetic methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in the design and development of novel negative allosteric modulators of mGlu(5). Emmitte, KA.[2021]

The novel negative allosteric modulator MRZ-8456 effectively reduced seizures and improved dendritic spine maturity in a mouse model of fragile X syndrome, showing similar efficacy to another drug, AFQ-056.

Both MRZ-8456 and AFQ-056 demonstrated significant reductions in amyloid-beta protein precursor expression, indicating potential benefits in addressing neurodevelopmental issues associated with excessive glutamate activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rescue of Fmr1KO phenotypes with mGluR5 inhibitors: MRZ-8456 versus AFQ-056. Westmark, PR., Dekundy, A., Gravius, A., et al.[2019]

Small molecule negative allosteric modulators (NAMs) of the mGlu5 receptor show potential for treating various conditions, including pain, anxiety, and depression, highlighting their therapeutic versatility.

Despite the progress in developing mGlu5 NAMs, including a variety of new chemical entities, the successful launch of a new drug remains uncertain, indicating ongoing challenges in this research area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mGlu5 negative allosteric modulators: a patent review (2010-2012). Emmitte, KA.[2013]

The muscarinic acetylcholine receptor subtype 5 (M5) is a promising target for treating conditions like Alzheimer's disease, schizophrenia, and addiction, as indicated by studies using knockout animals.

Recent advancements in small-molecule allosteric modulators have enabled the selective investigation of M5 pharmacology, with the development of both positive and negative allosteric modulators to better understand and potentially manipulate this receptor's function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Muscarinic Acetylcholine Receptor M5: Therapeutic Implications and Allosteric Modulation. Bender, AM., Garrison, AT., Lindsley, CW.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06414954

Safety and Efficacy of 3 Dose Levels of NMD670 in Adult ... This Phase 2 proof-of-concept, dose range finding study aims to evaluate the safety and efficacy of 3 dose levels of NMD670 vs placebo in adult patients ...

2. nmdpharma.com nmdpharma.com/news/nmd-pharma-initiates-phase-2b-trial-of-nmd670-in-generalized-myasthenia-gravis-patients

NMD Pharma Initiates Phase 2b Trial of NMD670 in ... NMD670 is a first-in-class development candidate which is expected to improve muscle power and endurance to help manage persistent and fluctuating symptoms.

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

Bromophenoxyazole Propanoic Acid - Drug Targets, ... In a Phase I clinical trial , patients with myasthenia gravis experienced clinically meaningful improvements in the Quantitative Myasthenia Gravis (QMG) score— ...

4. science.org science.org/doi/10.1126/scitranslmed.adk9109

The ClC-1 chloride channel inhibitor NMD670 improves ... NMD670 had a favorable safety profile and led to clinically relevant improvements in the quantitative myasthenia gravis (QMG) total score. This ...

5. 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 is currently being evaluated in three separate Phase 2 clinical trials for neuromuscular diseases with high unmet clinical needs, ...

6. nmdpharma.com nmdpharma.com/news/nmd670-top-line-data

NMD Pharma Reports Positive Top-Line Data from a ... NMD670 was safe and well tolerated in healthy volunteers and patients. Administration of single doses of NMD670 was associated with clinically ...