DAS-001 for Myasthenia Gravis

No longer recruiting at 1 trial location

Overseen By Christina Smith, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: DAS-MG, Inc

Must be taking: Pyridostigmine

Must not be taking: Marijuana, Narcotics, SSRIs, others

Disqualifiers: GI diseases, Hepatic, Renal, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment combination of ondansetron (a medication often used to prevent nausea and vomiting) and pyridostigmine for individuals with myasthenia gravis, a condition that causes muscle weakness. The goal is to determine if adding ondansetron reduces the stomach-related side effects some people experience with pyridostigmine. Participants will receive either the treatment combination or a placebo, alongside pyridostigmine, at random. Suitable candidates have been diagnosed with myasthenia gravis, experience nausea, vomiting, or diarrhea from pyridostigmine, and can maintain a daily symptom diary. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use marijuana, narcotics, aminoglycoside antibiotics, or SSRIs. You can continue taking pyridostigmine if you are already on it.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pyridostigmine is a well-known treatment for myasthenia gravis. One study found that 61% of patients used it, and many found it helpful. Most people tolerate it well, though some might experience mild side effects like stomach cramps or diarrhea.

Ondansetron often prevents nausea and has a good safety record, with most people experiencing few side effects. Researchers are studying the combination of pyridostigmine and ondansetron to ensure its safety and effectiveness. Previous research on pyridostigmine alone has demonstrated its general safety, which is encouraging for this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Myasthenia Gravis, which often involve immune suppressants and cholinesterase inhibitors like pyridostigmine, DAS-001 is unique because it combines ondansetron with pyridostigmine. Ondansetron typically treats nausea but may offer a new way to manage Myasthenia Gravis symptoms by potentially enhancing neuromuscular function. Researchers are excited about this combination because it could provide a dual-action approach, targeting both symptom relief and improving muscle strength, offering hope for better management of the condition.

What evidence suggests that this trial's treatments could be effective for myasthenia gravis?

Research has shown that pyridostigmine often treats myasthenia gravis, a condition causing muscle weakness, by improving nerve-muscle communication. In this trial, one treatment arm will receive a combination of pyridostigmine and ondansetron, which might reduce pyridostigmine's side effects. A study found that this combination could benefit people with myasthenia gravis by decreasing unwanted effects. However, researchers are still collecting more detailed information on how well this specific combination works for myasthenia gravis. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with anti-AchR antibody positive myasthenia gravis who are taking pyridostigmine and have had related GI side effects recently. Participants must be clinically stable, able to maintain a symptom diary, swallow liquids, and not have certain heart conditions or electrolyte imbalances. Pregnant women or those not using birth control, along with patients on specific medications like SSRIs or narcotics, cannot join.

Inclusion Criteria

Subjects must be in good health as determined by their medical history, physical examination, vital signs, and laboratory tests. A subject with a medical abnormality may be included only if the investigator or designee considers that the abnormality will not introduce significant additional risk to the subject's health or interfere with study objectives.

Subjects must have signed an informed consent form indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study and comply with the study procedures and restrictions.

I can tolerate taking pyridostigmine 30mg three times a day.

Exclusion Criteria

I have heart rhythm issues or take medication that affects my heart's rhythm.

I haven't taken drugs affecting nerve function, except for pyridostigmine, in the last month.

Subjects unlikely to co-operate during the study, and/or be questionably compliant in the opinion of the investigator.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either pyridostigmine with ondansetron or pyridostigmine with placebo for 6 weeks. Dose titration may occur weekly at the investigator's discretion.

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and changes in clinical evaluations.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ondansetron
• Pyridostigmine

Trial Overview The study tests DAS-001 in a phase II trial where participants receive either the test drug or a placebo without knowing which one they get. The goal is to see if DAS-001 can help manage gastrointestinal symptoms caused by pyridostigmine in people with myasthenia gravis.

How Is the Trial Designed?

Group I: treatment Active Control 1 Intervention

ondansetron + pyridostigmine

Group II: Placebo Placebo Group 1 Intervention

placebo+ pyridostigmine

Pyridostigmine is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Mestinon for:

• Myasthenia Gravis
• Dysautonomia
• Reversal of Nondepolarizing Muscle Relaxants
• Nerve Agent Pretreatment

Approved in Canada as Mestinon for:

• Myasthenia Gravis
• Dysautonomia
• Reversal of Nondepolarizing Muscle Relaxants

Approved in European Union as Mestinon for:

• Myasthenia Gravis
• Dysautonomia

Who Is Running the Clinical Trial?

DAS-MG, Inc

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

In a study of 677 patients with myasthenia gravis (MG) in Norway, the prevalence of symptomatic MG was found to be 131 per million, with a higher incidence in women (170 per million) compared to men (92 per million).

The incidence rate for new users of pyridostigmine in 2007 was 16 per million, with a significant increase in prevalence and incidence observed in individuals aged 50 and older, particularly those aged 70-79.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myasthenia gravis requiring pyridostigmine treatment in a national population cohort. Andersen, JB., Engeland, A., Owe, JF., et al.[2015]

Pyridostigmine is a commonly used and generally safe medication for treating myasthenia gravis, an autoimmune disorder affecting about 20 people per 100,000 in the USA annually.

However, there is a rare risk of cardiac conduction disorders in some patients taking pyridostigmine, highlighting the need for awareness of this potential adverse reaction in acute care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyridostigmine induced heart block requiring ICU admission. Chaucer, B., Whelan, D., Lamichhane, D.[2020]

In a study of 16 myasthenia gravis patients, plasma levels of pyridostigmine varied significantly, being generally higher in poorly controlled patients, indicating that drug absorption may be inconsistent.

The study found that high-dose alternate-day steroid treatment significantly reduced the bioavailability of pyridostigmine in poorly controlled patients, suggesting that certain medications can impact the effectiveness of pyridostigmine treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma pyridostigmine levels in myasthenia gravis. White, MC., De Silva, P., Havard, CW.[2019]

In a mouse model of anti-MuSK myasthenia gravis, treatment with pyridostigmine worsened muscle weakness and structural damage at the neuromuscular junction, suggesting it may not be effective for all forms of myasthenia gravis.

Conversely, 3,4-diaminopyridine improved neuromuscular transmission without exacerbating the condition, indicating it may be a more beneficial treatment option in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyridostigmine but not 3,4-diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle-specific kinase autoantibody. Morsch, M., Reddel, SW., Ghazanfari, N., et al.[2022]

In a study of 21 preadolescent patients with purely ocular myasthenia gravis, the initial treatment with pyridostigmine bromide was effective, leading to stabilization of ocular motor deficits in all patients, with some achieving complete resolution off medication.

The study found that generalization to systemic disease occurred in only 3 patients, indicating a lower risk of progression compared to adults, and most children presented with symptoms like ptosis and strabismus before age 5.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of pediatric ocular myasthenia gravis. Ortiz, S., Borchert, M.[2022]

Pyridostigmine bromide is a crucial anticholinesterase medication used globally for treating Myasthenia Gravis (MG), despite initial failures in early trials.

The article reviews the historical development and trials of pyridostigmine bromide, highlighting its evolution into a safe and effective treatment for MG over the past 70 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celebrating the 70 years of pyridostigmine on therapy of Myasthenia Gravis: historical aspects of the preliminary trials. Lorenzoni, PJ., Kay, CSK., Ducci, RD., et al.[2020]

In a study involving 410 myasthenia gravis patients, 61% reported using pyridostigmine, which showed a median effectiveness score of 60 out of 100, indicating it is generally effective for symptom management.

However, 91% of current users experienced side effects, with common issues including flatulence and muscle cramps, and 26% of those who discontinued the drug did so due to these side effects, highlighting the need for careful consideration before starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness and side effects of pyridostigmine in the treatment of myasthenia gravis: a cross-sectional study. Remijn-Nelissen, L., Verschuuren, JJGM., Tannemaat, MR.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04226170

NCT04226170 | Study of Pyridostigmine With Ondansetron ... This is a phase II, single center, randomized, double-blind, placebo-controlled, study in patients with a diagnosis of anti-AchR antibody positive myasthenia ...

2. myasthenia.org myasthenia.org/wp-content/uploads/Portals/0/DAS-MG%20Research%20Announcement%20Form%20for%20Web_MGFA.pdf

Study of Pyridostigmine with Ondansetron in Subjects with ... Subjects must be able to tolerate a pyridostigmine dose of 30mg TID. Must be clinically stable in judgement of treating neurologists for past 3 months. Must ...

3. myastheniagravisnews.com myastheniagravisnews.com/news/gtp-004-may-reduce-side-effects-myasthenia-gravis-therapy-mestinon/

For Myasthenia Gravis, GTP-004 May Reduce Side Effects ... Results of a Phase 1 clinical trial showed that the investigational therapy GTP-004 significantly reduced the side effects associated with the myasthenia ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK615403/

Comparing Two Medicines for Adults with Myasthenia Gravis We believed that MMF is probably more effective than AZA and tends to achieve effect earlier. A study of AZA showed that 33% of patients on AZA achieve ...

5. trial.medpath.com trial.medpath.com/clinical-trial/77a639a3d2872335/nct04226170-safety-tolerability-pyridostigmine-ondansetron-myasthenia-gravis

Study of Pyridostigmine With Ondansetron in Subjects With ... This is a phase II, single center, randomized, double-blind, placebo-controlled, study in patients with a diagnosis of anti-AchR antibody positive myasthenia ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03510546

NCT03510546 | Effect of Pyridostigmine (Mestinon) on ... The study aims to evaluate and quantify the effect of pyridostigmine on symptoms and muscle strength in newly-diagnosed patients and patients on stable ...

7. withpower.com withpower.com/trial/phase-3-muscle-weakness-3-2021-8961d

DAS-001 for Myasthenia Gravis · Info for Participants Pyridostigmine is commonly used to treat myasthenia gravis, with 61% of patients in a study reporting its use and a median effectiveness rating of 60 out of ...