Pyridostigmine and Amifampridine for Myasthenia Gravis

Trial Title: Pyridostigmine and Amifampridine for Myasthenia Gravis

NCT ID: NCT05919407

Condition: Myasthenia Gravis

Conditions: Official terms:
Myasthenia Gravis
Muscle Weakness
Amifampridine
Pyridostigmine Bromide

Study type: Interventional

Study phase: Phase 3

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Intervention:

Intervention type: Drug
Intervention name: Pyridostigmine
Description: Participants will receive pyridostigmine 10 mg tablets.
Arm group label: Pyridostigmine

Intervention type: Drug
Intervention name: Amifampridine (base) with modified release
Description: Participants will receive amifampridine (base) with modified release 15 mg or 30 mg tablets.
Arm group label: Amifampridine (base) with modified release

Intervention type: Drug
Intervention name: Placebo
Description: The placebo tablets will be identical apart from the active substance (pyridostigmine)
Arm group label: Placebo (pyridostigmine)

Intervention type: Drug
Intervention name: Placebo
Description: The placebo tablets will be identical apart from the active substance (amifampridine base)
Arm group label: Placebo (amifampridine)

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

Detailed description: In the first part of the study, patients who are currently using pyridostigmine will be randomly allocated to one of two consecutive treatment periods in which patients either first receive placebo and then their usual dose of pyridostigmine, or vice versa. Each treatment period lasts 5 days with a 2-day wash-out period between each treatment period. Measurements will be performed at every last day of a treatment period (day 5 and day 12). In the second part of the study the effect of two doses of amifampridine as add-on to pyridostigmine will be studied. Patients will be randomly assigned to either one of three treatment sequences; 1) amifampridine 30 mg - amifampridine 60 mg - placebo or 2) amifampridine 60 mg - placebo - amifampridine 30 mg or 3) placebo - amifampridine 30 mg - amifampridine 60 mg. Again, each treatment period consists of 5 days and will be separated by a 2-day wash-out period. Measurements will be performed at every last day of treatment (day 19, day 26 and day 33). Patients will have the option to participate in a substudy to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of amifampridine in AChR positive MG patients.

Criteria for eligibility:
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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Leiden University Medical Center

Address:
City: Leiden
Zip: 2333 ZA
Country: Netherlands

Status: Recruiting

Contact:
Last name: Martijn R. Tannemaat, MD, PhD

Phone: +31 71 5262197
Email: m.r.tannemaat@lumc.nl

Start date: March 22, 2023

Completion date: September 22, 2024

Lead sponsor:
Agency: Leiden University Medical Center
Agency class: Other

Collaborator:
Agency: NMD Pharma A/S
Agency class: Industry

Source: Leiden University Medical Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05919407