Pyridostigmine and Amifampridine for Myasthenia Gravis

NCT ID: NCT05919407

Last Updated: 2023-06-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-22
• Study Completion Date: 2024-09-22

Brief 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.

Conditions

Myasthenia Gravis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pyridostigmine

The dose of pyridostigmine will be based on the patient's prior experience with pyridostigmine under the assumption that the patient already gained sufficient experience during their disease course to know which dose is effective for them as patients are advised by their treating neurologist to continually adjust their dose based on their symptoms and side effects.

Group Type: EXPERIMENTAL

Pyridostigmine

Intervention Type: DRUG

Participants will receive pyridostigmine 10 mg tablets.

Placebo (pyridostigmine)

Same as "Experimental", however capsules contain placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The placebo tablets will be identical apart from the active substance (pyridostigmine)

Amifampridine (base) with modified release

Patients will receive amifampridine 2 dd 15 mg and amifampridine 2 dd 30 mg as add-on to the pre-study dose of pyridostigmine.

Group Type: EXPERIMENTAL

Amifampridine (base) with modified release

Intervention Type: DRUG

Participants will receive amifampridine (base) with modified release 15 mg or 30 mg tablets.

Placebo (amifampridine)

Same as "Experimental", however capsules contain placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The placebo tablets will be identical apart from the active substance (amifampridine base)

Interventions

Pyridostigmine

Participants will receive pyridostigmine 10 mg tablets.

Intervention Type: DRUG

Amifampridine (base) with modified release

Participants will receive amifampridine (base) with modified release 15 mg or 30 mg tablets.

Intervention Type: DRUG

Placebo

The placebo tablets will be identical apart from the active substance (pyridostigmine)

Intervention Type: DRUG

Placebo

The placebo tablets will be identical apart from the active substance (amifampridine base)

Intervention Type: DRUG

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NMD Pharma A/S

INDUSTRY

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Martijn R. Tannemaat, MD PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Leiden University Medical Center

Leiden, South Holland, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Martijn R. Tannemaat, MD, PhD

Role: CONTACT

m.r.tannemaat@lumc.nl

+31715262197

Jan J.G.M. Verschuuren, MD, PhD

Role: CONTACT

j.j.g.m.verschuuren@lumc.nl

+31715262197

Facility Contacts

Martijn R. Tannemaat, MD, PhD

Role: primary

m.r.tannemaat@lumc.nl

+31 71 5262197

Other Identifiers

NL78666.058.21

Identifier Type: -

Identifier Source: org_study_id