Evaluating Pyridostigmine and Amifampridine for Myasthenia Gravis

IMproving Symptomatic Treatment With Pyridostigmine and Amifampridine: a Randomized Double-blinded, Placebo Controlled Crossover Trial in Patients With Myasthenia Gravis (IMPACT-MG)

Phase 3 Interventional Leiden University Medical Center · NCT05919407

This study is testing if adding a new drug called amifampridine to the usual treatment with pyridostigmine can help people with Myasthenia Gravis feel better.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment24 (estimated)
Ages18 Years and up
SexAll
SponsorLeiden University Medical Center Academic / other
Drugs / interventionsRituximab
Locations1 site (Leiden, South-Holland)
Trial IDNCT05919407 on ClinicalTrials.gov

What this trial studies

This clinical trial is a randomized, double-blind, placebo-controlled, crossover intervention that assesses the effects of pyridostigmine and amifampridine in patients with Myasthenia Gravis (MG). In the first part, participants currently using pyridostigmine will alternate between receiving a placebo and their usual medication over two treatment periods. The second part will evaluate the impact of two doses of amifampridine as an add-on therapy to pyridostigmine, with patients assigned to different treatment sequences. The study includes pharmacokinetic and pharmacodynamic assessments for AChR positive MG patients.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with AChR positive Myasthenia Gravis who are currently using pyridostigmine.

Not a fit: Patients with Myasthenia Gravis who do not meet the inclusion criteria or are not currently using pyridostigmine may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve treatment options and outcomes for patients with Myasthenia Gravis.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination of treatments is novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Age \>18 years
2. AChR positive myasthenia gravis (ocular or generalized)
3. Current use of pyridostigmine
4. MGFA Clinical Classification I-IV
5. Receiving a stable dose of MG treatment (other than pyridostigmine). If applicable:

   1. A stable steroid regimen for 1 month
   2. Nonsteroidal immunosuppressants: i. Azathioprine, mycophenolate mofetil, cyclosporine or other nonsteroid immunosuppressive agents start \> 3 months ago and a stable regimen for 1 month. ii. Rituximab start \> 6 months ago, complement inhibitors and Fc receptor inhibitors start \> 6 months ago and a stable regimen for 3 months.

Additional inclusion criteria for part 2 To be eligible for participation in part 2 of the study patients must score \>10 points on the MGII questionnaire at inclusion.

We will include a maximum of 5 patients with a MGFA class I (i.e. 20 percent of the total number of included patients) to ensure that this study accurately reflects the clinical population.

Exclusion Criteria:

1. Use of intravenous immunoglobulin or plasma exchange \<4 weeks or planned during the trial.
2. Thymectomy \< 6 months, or thymectomy (expected) to take place during the trial
3. Use of other acetylcholinesterase inhibitors than pyridostigmine
4. Pregnancy, lactation or intention to become pregnant during the study
5. Treatment with amifampridine is contraindicated. Contraindications include a history of epilepsy, uncontrolled asthma, inherited QT syndrome / a prolonged QT interval (as indicated by ECG), any drug known to cause QT c-prolongation, any drug known to lower the epileptic threshold, a known hypersensitivity reaction to the active substance or to any of the excipients.
6. The patient is unable to fill out the study questionnaires or be interviewed in Dutch, or is unable to undergo the tests needed for the study, or is unable to give informed consent for participation in the study.
7. The investigator can exclude patients for this trial which are deemed not suitable for any reason.

Where this trial is running

Leiden, South-Holland

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Myasthenia Gravis
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.