Pyridostigmine and Amifampridine for Myasthenia Gravis

NCT05919407 | Unknown Phase 3

• 1 other identifier: NL78666.058.21
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

Myasthenia Gravis

Outcome Measures

Primary Outcomes (1)

• A clinically relevant change in Myasthenia Gravis Impairment Index (MGII) compared to placebo.

  Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),

Secondary Outcomes (16)

• Change on 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) compared to placebo

  Assessed on Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),

• Change on the 15-item revised version of the Myasthenia Gravis Quality of Life questionnaire (MG-QoL15r) compared to placebo

  Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),

• A clinically relevant change (≥2 points change) on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score compared to placebo.

  Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),

• A clinically relevant change (≥3 points change) on the Quantitative Myasthenia Gravis (QMG) score compared to placebo.

  Assessed on Day 1, Day 5, Day 12, Day 19, Day 26 and Day 33 (cross-over),

• Number of patients not able to complete first wash-out period due to an increase in myasthenic symptoms.

  Assessed on Day 1 (crossover)

Study Arms (4)

Pyridostigmine

EXPERIMENTAL

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.

Drug: Pyridostigmine

Placebo (pyridostigmine)

PLACEBO COMPARATOR

Same as "Experimental", however capsules contain placebo.

Drug: Placebo

Amifampridine (base) with modified release

EXPERIMENTAL

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

Drug: Amifampridine (base) with modified release

Placebo (amifampridine)

PLACEBO COMPARATOR

Same as "Experimental", however capsules contain placebo.

Drug: Placebo

Interventions

Pyridostigmine DRUG

Participants will receive pyridostigmine 10 mg tablets.

Pyridostigmine

Amifampridine (base) with modified release DRUG

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

Amifampridine (base) with modified release

Placebo DRUG

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

Placebo (pyridostigmine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years
• AChR positive myasthenia gravis (ocular or generalized)
• Current use of pyridostigmine
• MGFA Clinical Classification I-IV
• Receiving a stable dose of MG treatment (other than pyridostigmine). If applicable:
• A stable steroid regimen for 1 month
• 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.

You may not qualify if:

• Use of intravenous immunoglobulin or plasma exchange \<4 weeks or planned during the trial.
• Thymectomy \< 6 months, or thymectomy (expected) to take place during the trial
• Use of other acetylcholinesterase inhibitors than pyridostigmine
• Pregnancy, lactation or intention to become pregnant during the study
• 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.
• 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.
• The investigator can exclude patients for this trial which are deemed not suitable for any reason.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• NMD Pharma A/S: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Pyridostigmine Bromide; Amifampridine; Alkalies

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 4-Aminopyridine; Aminopyridines; Amines; Organic Chemicals; Inorganic Chemicals

Central Study Contacts

Martijn R. Tannemaat, MD, PhD

CONTACT

+31715262197; m.r.tannemaat@lumc.nl

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

CONTACT

+31715262197; j.j.g.m.verschuuren@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 6, 2023
• First Posted: June 26, 2023
• Study Start: March 22, 2023
• Primary Completion: September 22, 2024
• Study Completion: September 22, 2024
• Last Updated: June 26, 2023

Record last verified: 2023-06

Locations

NL (1)