NMD670 for Myasthenia Gravis
(SYNAPSE-MG Trial)
Recruiting in Palo Alto (17 mi)
+29 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: NMD Pharma A/S
Disqualifiers: Pregnancy, Breastfeeding, Poor compliance, others
Prior Safety Data
Approved in 1 Jurisdiction
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.
12345Eligibility 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.
+4 more
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
+2 more
Trial 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)
Participant Groups
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.
4Treatment groups
Experimental Treatment
Placebo Group
Group I: NMD670 mid doseExperimental Treatment1 Intervention
Group II: NMD670 low doseExperimental Treatment1 Intervention
Group III: NMD670 high doseExperimental Treatment1 Intervention
Group IV: PlaceboPlacebo Group1 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Profound Research LLCCarlsbad, CA
SFM Clinical Research, LLCBoca Raton, FL
NextGen Precision HealthColumbia, MO
Semmes Murphey ClinicMemphis, TN
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
NMD Pharma A/SLead Sponsor
References
Rescue of Fmr1KO phenotypes with mGluR5 inhibitors: MRZ-8456 versus AFQ-056. [2019]Metabotropic glutamate receptor 5 (mGluR5) is a drug target for central nervous system disorders such as fragile X syndrome that involve excessive glutamate-induced excitation. We tested the efficacy of a novel negative allosteric modulator of mGluR5 developed by Merz Pharmaceuticals, MRZ-8456, in comparison to MPEP and AFQ-056 (Novartis, a.k.a. mavoglurant) in both in vivo and in vitro assays in a mouse model of fragile X syndrome, Fmr1KO mice. The in vivo assays included susceptibility to audiogenic-induced seizures and pharmacokinetic measurements of drug availability. The in vitro assays included dose response assessments of biomarker expression and dendritic spine length and density in cultured primary neurons. Both MRZ-8456 and AFQ-056 attenuated wild running and audiogenic-induced seizures in Fmr1KO mice with similar pharmacokinetic profiles. Both drugs significantly reduced dendritic expression of amyloid-beta protein precursor (APP) and rescued the ratio of mature to immature dendritic spines. These findings demonstrate that MRZ-8456, a drug being developed for the treatment of motor complications of L-DOPA in Parkinson's disease and which completed a phase I clinical trial, is effective in attenuating both well-established (seizures and dendritic spine maturity) and exploratory biomarker (APP expression) phenotypes in a mouse model of fragile X syndrome.
mGlu5 negative allosteric modulators: a patent review (2013 - 2016). [2017]Label="INTRODUCTION" NlmCategory="BACKGROUND">The pursuit of small molecule mGlu5 NAMs as treatments for a variety of psychiatric and neurodegenerative disorders has developed into a mature field. In addition to extensive preclinical studies, multiple compounds have advanced into clinical trials with the most advanced studies occurring in patients with FXS, PD-LID, and MDD. Areas covered: This review begins with an update of the clinical activity with mGlu5 NAMs, and then moves into a summary of patent applications filed since 2013. The summaries are organized into three separate sections: (1) inventions centered on improvements to existing clinical compounds; (2) new small molecules that maintain the prototypical disubstituted alkyne chemotype found in many mGlu5 NAM compounds; and (3) new small molecules that are not from a disubstituted alkyne chemotype. Expert opinion: It is a critical moment for mGlu5 NAM research as recent reports from clinical trials have included some significant disappointments that have blunted prior optimism. Still, research in this area remains active, and recent years have added several more attractive small molecules to this field. There is now an arsenal of diverse chemotypes available to continue to probe this target in the hopes that a drug may yet emerge.
mGlu5 negative allosteric modulators: a patent review (2010-2012). [2013]The design and development of small molecule negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 5 (mGlu5) has been an area of intense interest for over a decade. Potential roles have been established for mGlu5 NAMs in the treatment of diseases such as pain, anxiety, gastroesophageal reflux disease (GERD), Parkinson's disease levodopa-induced dyskinesia (PD-LID), fragile X syndrome (FXS), autism, addiction, and depression.
Recent advances in the design and development of novel negative allosteric modulators of mGlu(5). [2021]Negative allosteric modulators (NAMs) of metabotropic glutamate receptor subtype 5 (mGlu(5)) have remained attractive to researchers as potential therapies for a number of central nervous system related diseases, including anxiety, pain, gastroesophageal reflux disease (GERD), addiction, Parkinson's disease (PD), and fragile X syndrome (FXS). In addition to the many publications with supportive preclinical data with key tool molecules, recent positive reports from the clinic have bolstered the confidence in this approach. During the two year time span from 2009 through 2010, a number of new mGlu(5) NAM chemotypes have been disclosed and discussed in the primary and patent literature. A summary of several efforts representing many diverse chemotypes are presented here, along with a discussion of representative structure activity relationships (SAR) and synthetic approaches to the templates where possible.
The Muscarinic Acetylcholine Receptor M5: Therapeutic Implications and Allosteric Modulation. [2020]The muscarinic acetylcholine receptor (mAChR) subtype 5 (M5) was the most recent mAChR to be cloned and has since emerged as a potential therapeutic target for a number of indications. Early studies with knockout animals have provided clues to the receptor's role in physiological processes related to Alzheimer's disease, schizophrenia, and addiction, and until recently, useful subtype-selective tools to further probe the pharmacology of M5 have remained elusive. Small-molecule allosteric modulators have since gained traction as a means by which to selectively examine muscarinic pharmacology. This review highlights the discovery and optimization of M5 positive allosteric modulators (PAMs) and negative allosteric modulators (NAMs).