Myasthenia Gravis MedDRA version: 24.0 Level: LLT Classification code 10085562 Term: AChR myasthenia gravis System Organ Class: 100000004852
Conditions
Interventions
Product Name: Amifampridine
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Trade Name: Mestinon
Product Name: Pyridostigmine
P
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
Inclusion 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: a. A stable steroid regimen for 1 month b. 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, complement inhibitors and Fc receptor inhibitors start > 6 months ago and a stable regimen for 3 months. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 17 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1. Use of intravenous immunoglobulin or plasma exchange <4 weeks 2. Thymectomy < 6 months, or thymectomy (expected) to take place during the trial 3. Use of other AChE 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 QTc-prolongation, concomitant use of sultopride, 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To determine the efficacy of pyridostigmine compared to placebo on MG symptoms in patients with AChR MG as measured by the MGII. 2. To determine the efficacy of amifampridine compared to placebo on MG symptoms in patients with AChR MG using pyridostigmine as measured by the MGII.;Secondary Objective: a)To assess patient satisfaction with pyridostigmine and add-on amifampridine as measured by TSQM-9. b)To determine the tolerability of pyridostigmine and add-on amifampridine as measured by a side effects questionnaire. c)To evaluate the impact of pyridostigmine and add-on amifampridine on quality of life as measured by the MG-QoL15r and EQ-5D-5L. d)To determine efficacy of pyridostigmine and amifampridine add-on compared to placebo on the QMG, MG-ADL and MGII ocular and general subscores. e)To evaluate the PK and PD of amifampridine (for those subjects in the PK/PD Substudy only). f)To evaluate the PK parameters of pyridostigmine when taking with and without amifampridine (for those subjects in the PK/PD Substudy). g)To assess cost-utility of amifampridine as add on in patients with AChR-MG. h)To determine whether long-term efficacy, patient satisfaction, tolerability and impact on quality of life is sustained over a six-month period.;Primary end point(s): A clinically relevant change in MGII compared to placebo; a change of =8 is considered clinically relevant;Timepoint(s) of evaluation of this end point: Weekly on D5 during part 1 and part 2 of the study In the observational open label extension phase outcome measures will be evaluated at 3 and 6 months after completion of part 2. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a) Change on 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) compared to placebo b) Change on MG-QoL15r compared to placebo c) Change on EQ-5D-5L compared to placebo d) A clinically relevant change in the clinical scores MG-ADL (=2 points change) and QMG (=3 points change) compared to placebo. e) Change on a global impression 10 point scale (VAS-score) to evaluate whether patients are feeling worse or better overall during treatment in comparison to placebo. f) To record side effects of either pyridostigmine and amifampridine a questionnaire will be obtained. The questionnaire is specifically developed for this purpose, which explores presence, duration and severity of symptoms that might be adverse effects of pyridostigmine or amifampridine treatment g) Number of patients not able to complete first wash-out period due to an increase in myasthenic symptoms. h) Number of times escape medication is used (including effect on symptoms) i) Serum concentrations of pyridostigmine j) For patients participating in the PK/PD substudy, the following endpoints will be included: a. Maximum concentration (Cmax, Cmax ss) b. Area under the concentration-time curve (AUC0-tau ss) at steady state c. Time of maximum concentration (Tmax, Tmax ss) d. Analyses will be performed to evaluate the dose response relationship between serum concentrations of amifampridine and iliopsoas and hand grip strength as measured with hand-held dynamometer. k) For the cost-utility analysis health care use and productivity will be assessed using the adapted iMCQ and iPCQ at baseline. ;Timepoint(s) of evaluation of this end point: Weekly on D5 during part 1 and part 2 of the study. In the observational open label extension phase outcome measures will be evaluated at 3 and 6 months after completion of part 2. | — |
Countries
Netherlands
Contacts
Public ContactIMPACT-MG study contact
Leiden University Medical Center
Outcome results
None listed