DAS-001 for Myasthenia Gravis

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests whether adding ondansetron to pyridostigmine can help patients with myasthenia gravis who suffer from stomach problems caused by pyridostigmine. Pyridostigmine helps muscles work better, but it can cause nausea. Ondansetron is used to prevent this nausea. The goal is to see if patients can tolerate higher doses of pyridostigmine without feeling sick. Ondansetron is widely used to prevent nausea and vomiting in various conditions, including chemotherapy, pregnancy, and postoperative recovery.

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.

What data supports the effectiveness of the drug pyridostigmine for treating myasthenia gravis?

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 100. However, 91% of users reported side effects, which sometimes led to discontinuation. ^{1 2 3 4 5}

Is pyridostigmine generally safe for humans?

Pyridostigmine is generally safe for treating myasthenia gravis, but some people experience side effects like gas, muscle cramps, and blurred vision. Rarely, it can cause heart problems, and some people stop using it due to side effects like diarrhea and muscle twitching. ^{1 3 4 5 6}

How does the drug pyridostigmine differ from other treatments for myasthenia gravis?

Pyridostigmine is unique because it is a cholinesterase inhibitor that increases the amount of acetylcholine (a chemical that helps muscles contract) at the neuromuscular junction, which can improve muscle strength in myasthenia gravis. However, it may not be effective for all forms of the condition and can sometimes worsen symptoms in specific cases, such as those involving anti-MuSK antibodies. ^{2 3 5 6 7}

Research Team

Eligibility Criteria

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 have myasthenia gravis and have had stomach issues from pyridostigmine in the last week.

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.

Trial Timeline

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

Treatment Details

Interventions

• Ondansetron (5-HT3 Receptor Antagonist)
• Pyridostigmine (Cholinesterase Inhibitor)

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.

Participant Groups

Group I: treatment Active Control 1 Intervention

ondansetron + pyridostigmine

Group II: Placebo Placebo Group 1 Intervention

placebo+ pyridostigmine

Pyridostigmine is already approved in Canada for the following indications:

Approved in Canada as Mestinon for:

• Myasthenia Gravis
• Dysautonomia
• Reversal of Nondepolarizing Muscle Relaxants

Who Is Running the Clinical Trial?

DAS-MG, Inc

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

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]

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 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]

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]

References

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

Long-term outcomes of pediatric ocular myasthenia gravis. [2022]

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

Myasthenia gravis requiring pyridostigmine treatment in a national population cohort. [2015]

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

Pyridostigmine induced heart block requiring ICU admission. [2020]

4. England pubmed.ncbi.nlm.nih.gov

The effectiveness and side effects of pyridostigmine in the treatment of myasthenia gravis: a cross-sectional study. [2022]

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

Plasma pyridostigmine levels in myasthenia gravis. [2019]

6. England 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. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Celebrating the 70 years of pyridostigmine on therapy of Myasthenia Gravis: historical aspects of the preliminary trials. [2020]