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

NL78666.058.21

A randomized, double-blind, placebo controlled, crossover intervention study evaluating the effect of pyridostigmine (part 1) and amifampridine (part 2) in Myasthenia Gravis (MG).

2023-03-22

2024-09-22

2024-09-22

Recruiting

Early phase I

24

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 24, 'type': 'ESTIMATED'}}

2023-06-26