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Study to Evaluate Amifampridine Phosphate in Patients With MuSK-MG

Primary Purpose

Myasthenia Gravis, Generalized

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Amifampridine Phosphate
Placebo Oral Tablet
Sponsored by
Catalyst Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myasthenia Gravis, Generalized focused on measuring MuSK antibody positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Cleveland Clinic
  • Univerity of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

amifamapridine phosphate tablets

placebo tablets

Arm Description

Outcomes

Primary Outcome Measures

Myasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results
Myasthenia Gravis-Activities of Daily Living (MG-ADL) is a self-report scale to assess the patient's MG symptoms and functional performance of activities of daily living. The eight items are scored on a scale of 0-3 with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. Each item was assessed by the patient at the last day (Day 0) of the Run-in period and at the post-treatment visit. The post-treatment result will be the result obtained on Day 10. If the patient discontinued treatment early, the post-treatment result may be obtained at an earlier time point. The total MG-ADL score was calculated as the sum of each item score, with a maximum score of 24 (most severe symptoms/impairment) and minimum score of 0 (least severe symptoms/impairment). The change from baseline (CFB) at Day 10 was assessed. A Wilcoxon-Mann-Whitney Rank Sum Test of equality of change from baseline distributions between subjects diagnos

Secondary Outcome Measures

Quantitative Myasthenia Gravis (QMG) Total Score Summary Statistics by Time Point and MG Type: Wilcoxon-Mann-Whitney Rank Sum Test Results
Quantitative Myasthenia Gravis (QMG) assesses the patient's general body strength and fatigability. Each test item is scored on a scale of 0-3 with 3 representing the most severe symptom results and 0 representing no symptom results. Each item was assessed by the patient at Screening, the first (Day 1) and last day (Day 0) of the Run-in period and at the post-treatment visit. The post-treatment result will be the result obtained on Day 10. If the patient discontinued treatment early, the post-treatment result may be obtained at an earlier time point. The total QMG score was calculated as the sum of each item score, with a maximum score of 39 (most severe symptoms) and minimum score of 0 (least severe symptoms). The change from baseline (CFB) at Day 10 was assessed. A Wilcoxon-Mann-Whitney Rank Sum Test of equality of change from baseline distributions between subjects diagnosed with MuSK-MG treated with amifampridine and placebo was conducted.

Full Information

First Posted
September 28, 2017
Last Updated
July 21, 2021
Sponsor
Catalyst Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03304054
Brief Title
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

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
April 18, 2018 (Actual)
Primary Completion Date
January 31, 2020 (Actual)
Study Completion Date
March 15, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Catalyst Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myasthenia Gravis, Generalized
Keywords
MuSK antibody positive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
93 (Actual)

8. Arms, Groups, and Interventions

Arm Title
amifamapridine phosphate tablets
Arm Type
Experimental
Arm Title
placebo tablets
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Amifampridine Phosphate
Intervention Description
tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
tablets matching amifampridine phosphate, 3 to 4 times a day
Primary Outcome Measure Information:
Title
Myasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results
Description
Myasthenia Gravis-Activities of Daily Living (MG-ADL) is a self-report scale to assess the patient's MG symptoms and functional performance of activities of daily living. The eight items are scored on a scale of 0-3 with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. Each item was assessed by the patient at the last day (Day 0) of the Run-in period and at the post-treatment visit. The post-treatment result will be the result obtained on Day 10. If the patient discontinued treatment early, the post-treatment result may be obtained at an earlier time point. The total MG-ADL score was calculated as the sum of each item score, with a maximum score of 24 (most severe symptoms/impairment) and minimum score of 0 (least severe symptoms/impairment). The change from baseline (CFB) at Day 10 was assessed. A Wilcoxon-Mann-Whitney Rank Sum Test of equality of change from baseline distributions between subjects diagnos
Time Frame
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 Outcome Measure Information:
Title
Quantitative Myasthenia Gravis (QMG) Total Score Summary Statistics by Time Point and MG Type: Wilcoxon-Mann-Whitney Rank Sum Test Results
Description
Quantitative Myasthenia Gravis (QMG) assesses the patient's general body strength and fatigability. Each test item is scored on a scale of 0-3 with 3 representing the most severe symptom results and 0 representing no symptom results. Each item was assessed by the patient at Screening, the first (Day 1) and last day (Day 0) of the Run-in period and at the post-treatment visit. The post-treatment result will be the result obtained on Day 10. If the patient discontinued treatment early, the post-treatment result may be obtained at an earlier time point. The total QMG score was calculated as the sum of each item score, with a maximum score of 39 (most severe symptoms) and minimum score of 0 (least severe symptoms). The change from baseline (CFB) at Day 10 was assessed. A Wilcoxon-Mann-Whitney Rank Sum Test of equality of change from baseline distributions between subjects diagnosed with MuSK-MG treated with amifampridine and placebo was conducted.
Time Frame
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).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Male or female ≥18 years of age. Positive serologic test for anti-MuSK antibodies or anti-AChR antibodies as confirmed at Screening or by previous antibody test, with report available. Confirmatory EMG or EMG report. Myasthenia Gravis Foundation of America (MGFA) Class II to IV at Screening. MG-ADL score of ≥6 at Screening, with more than 50% of this score attributed to non-ocular items. Patients receiving steroids or pyridostigmine should not have any modification of drug regimen during the month before Screening. 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. 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: Epilepsy and currently on medication. Concomitant use of medicinal products with a known potential to cause QTc prolongation. Patients with long QT syndromes. History of thymectomy within 12 months before Screening. An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormalities, in the opinion of the Investigator. Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study. 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. Use of rituximab or other similar biologic medications for immunomodulation within 6 months prior to Screening. Treatment with an investigational drug (other than amifampridine) or device within 30 days before Screening or while participating in this study. 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. History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Renato Mantegazza, MD
Organizational Affiliation
Carlo Besta Neurologic Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Univerity of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study to Evaluate Amifampridine Phosphate in Patients With MuSK-MG

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