Clinical trial NCT03304054: Study to Evaluate Amifampridine Phosphate in Patients With MuSK-MG
Official title: A Randomized, Placebo-control, Parallel Group Study to Evaluate the Effect of Amifampridine Phosphate in Patients With MuSK Antibody Positive Myasthenia Gravis, and a Sample of AChR Antibody Positive Myasthenia Gravis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myasthenia Gravis, Generalized
Keywords: MuSK antibody positive
Lead sponsor: Catalyst Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-10-06
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Efficacy and safety of amifampridine phosphate in improving the activities of daily living for patients with antibody positive MuSK myasthenia gravis.

Detailed description: Randomized, double-blind, placebo-controlled, parallel group study is designed to evaluate the safety, tolerability and efficacy of amifampridine phosphate in patients with MuSK-MG. In addition, a sample of AChR-MG patients will be assess for efficacy and safety of amifampridine phosphate. Planned duration of participation for each patient is at least 38 days, excluding the screening period. Eligible patients will be titrated to an efficacious dose of amifampridine phosphate and those who demonstrate improvement will be randomized to either placebo or amifampridine, in a double-blind fashion, for 10 days.

Eligibility criteria: Inclusion Criteria:

1. Willing and able to provide written informed consent after the nature of the study has been explained and before the start of any research-related procedures.
2. Male or female ≥18 years of age.
3. Positive serologic test for anti-MuSK antibodies or anti-AChR antibodies as confirmed at Screening or by previous antibody test, with report available.
4. Confirmatory EMG or EMG report.
5. Myasthenia Gravis Foundation of America (MGFA) Class II to IV at Screening.
6. MG-ADL score of ≥6 at Screening, with more than 50% of this score attributed to non-ocular items.
7. Patients receiving steroids or pyridostigmine should not have any modification of drug regimen during the month before Screening.
8. Female patients of childbearing potential must have a negative pregnancy test (serum human chorionic gonadotropin \[HCG\] at screening); and must practice an effective, reliable contraceptive regimen during the study and for up to 30 days following discontinuation of treatment.
9. Ability to participate in the study based on overall health of the patient and disease prognosis, as applicable, in the opinion of the Investigator; and able to comply with all requirements of the protocol, including completion of study questionnaires.

Exclusion Criteria:

1. Epilepsy and currently on medication.
2. Concomitant use of medicinal products with a known potential to cause QTc prolongation.
3. Patients with long QT syndromes.
4. History of thymectomy within 12 months before Screening.
5. An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormalities, in the opinion of the Investigator.
6. Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study.
7. Patients receiving immunomodulatory treatment (e.g. plasma exchange \[PE\], therapeutic plasma exchange \[TPE\], intravenous immunoglobulin G \[IVIG\]) should not have any treatment in the previous 4 weeks prior to Randomization or at any time during the study.
8. Use of rituximab or other similar biologic medications for immunomodulation within 6 months prior to Screening.
9. Treatment with an investigational drug (other than amifampridine) or device within 30 days before Screening or while participating in this study.
10. Any medical condition that, in the opinion of the Investigator, might interfere with the patient's participation in the study, poses an added risk for the patient, or confound the assessment of the patient.
11. History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s).

Primary outcomes:
measure: Myasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results
timeFrame: Last day (Day 0) of the Run-in period and at the post-treatment visit (i.e., day 10 or the time point at which a patient discontinued treatment early).
Secondary outcomes:
measure: Quantitative Myasthenia Gravis (QMG) Total Score Summary Statistics by Time Point and MG Type: Wilcoxon-Mann-Whitney Rank Sum Test Results
timeFrame: Last day (Day 0) of the Run-in period and at the post-treatment visit (i.e., day 10 or the time at which a patient discontinued treatment early).
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Univerity of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Carlo Besta Neurologic Institute
name: Renato Mantegazza, MD
role: PRINCIPAL_INVESTIGATOR
References: