NMD670 for Myasthenia Gravis

(SYNAPSE-MG Trial)

Recruiting at 38 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

Trial Summary

What is the purpose of this trial?

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 with MG with antibodies against AChR or MuSK, administered twice a day (BID) for 21 days.

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.

What data supports the effectiveness of the drug NMD670 for Myasthenia Gravis?

The research does not provide direct evidence for the effectiveness of NMD670 in treating Myasthenia Gravis. However, it mentions that drugs targeting mGluR5, like MRZ-8456, have shown effectiveness in other conditions involving the nervous system, such as fragile X syndrome, which may suggest potential for similar treatments. ^{1 2 3 4 5}

Eligibility Criteria

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

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 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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

References

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

Rescue of Fmr1KO phenotypes with mGluR5 inhibitors: MRZ-8456 versus AFQ-056. [2019]

2. England pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

The Muscarinic Acetylcholine Receptor M5: Therapeutic Implications and Allosteric Modulation. [2020]