Long Term Safety Study of Amifampridine Phosphate in MuSK-MG (Muscle Specific Tyrosine Kinase Myasthenia Gravis)

Long Term Safety Study of Amifampridine Phosphate in Patients With MuSK Antibody Positive and AChR (Acetylcholine Receptor) Antibody Positive Myasthenia Gravis

Evaluate the long-term safety of amifampridine phosphate in patients with MuSK antibody positive and AChR antibody positive myasthenia gravis.

Study Overview

• Status: Terminated
• Conditions: Myasthenia Gravis, MuSK; AChR Myasthenia Gravis
• Intervention / Treatment: Drug: Amifampridine Phosphate

Detailed Description

The Primary objective :

To characterize the long-term safety and tolerability of amifampridine phosphate in patients with MG

The Secondary Objective:

To assess the clinical efficacy of amifampridine phosphate over time in patients with MG based on change in Myasthenia Gravis Activities of Daily Living Score (MG-ADL)

This was a long-term extension study for subjects who participated in Protocol MSK-002 where the efficacy and safety of amifampridine was evaluated in subjects diagnosed with MuSK MG or AChR-MG. The optimal dose and schedule for amifampridine from the end of the Run-in Period from Study MSK-002 was initially used for each patient. The Investigator could adjust the dose of amifampridine during the course of the trial, in order to optimize neuromuscular benefit for the patient. Clinic visits for safety assessment and for evaluation of MG-ADL were made at Months 3, 6, 9, 12, 15, 21, 27, 33 and 39. Additional visits could occur at the discretion of the Investigator.

The Original protocol (12 Nov 2017) included analysis of MG-ADL change over time, however, Statistical Analysis Plan (SAP), dated 21 Feb 2023, removed the analysis of MG-ADL score change over time.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 11-201332
    • Department of Neuroimmunology and Neuromuscular Diseases Carlo Besta Neurological Institute Via Celoria
• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Univerity of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Participated in the MSK-002 study
2. 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.
3. Female patients of childbearing potential must have a negative pregnancy test (urine human chorionic gonadotropin [HCG] at the end of MSK-002 study); and must practice an effective, reliable contraceptive regimen during the study and for up to 30 days following discontinuation of treatment.
4. 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.

Individuals who met any of the exclusion criteria in the original protocol or those listed below are not eligible to participate in the study:

1. Epilepsy and currently on medication.
2. Clinically significant abnormalities in 12 lead ECG, in the opinion of the Investigator.
3. Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study.
4. Intolerable amifampridine-related side effects
5. Treatment with an investigational drug (other than amifampridine) or device while participating in this study.
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: amifampridine phosphate; tablets equivalent to 10mg amifampridine, 3 to 4 times per day. Initially, the daily amifampridine doses were to be the doses that were determined at the end of the Run-in Period from the MSK-002 study. The usual range was from 30 to 80 mg total daily dose, given in three (3) or four (4) doses, with no single dose > 20 mg	Drug: Amifampridine Phosphate; tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (Safety and Tolerability)	Evaluate the long-term safety and tolerability of amifampridine phosphate through the number of patients with treatment-emergent adverse events mapped to the Medical Dictionary for Regulatory Activities (MedDRA) SOCs and PTs. [ Time Frame: over 39 months ] Descriptive statistics will be used to summarize study data.	over 39 months

Collaborators and Investigators

• Sponsor: Catalyst Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Renato Mantegazza, MD, Carlo Besta Neurological Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2018
• Primary Completion (Actual): August 5, 2022
• Study Completion (Actual): August 5, 2022

Study Registration Dates

• First Submitted: June 5, 2018
• First Submitted That Met QC Criteria: July 5, 2018
• First Posted (Actual): July 9, 2018

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Myasthenia Gravis; 3,4-Diaminopyridine Phosphate; 3,4-Diaminopyridine; 3,4-DAP; Firdapse®; AChR; Amifampridine Phosphate Amifampridine; MuSK
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Membrane Transport Modulators; Neuromuscular Agents; Potassium Channel Blockers; Amifampridine
• Other Study ID Numbers: MSK-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No