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

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.

• Amifampridine Phosphate (Drug): tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day

Primary outcomes

• Number of Participants With Treatment-Emergent Adverse Events (Safety and Tolerability) [over 39 months]: 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.

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• Number of Participants With Treatment-Emergent Adverse Events (Safety and Tolerability) (Primary), Count of participants, Participants: Treatment Emergent Adverse Events 58

Adverse events

Time frame: Study Duration 39 months

Serious adverse events by term

Other adverse events by term

Limitations and caveats: The study was terminated due to lack of measure appropriate data. The analysis of the MG-ADL score was removed in Statistical Analysis Plan (SAP), dated 21FEB2023.

• Study Protocol: Original Protocol (PDF, 2017-11-12)
• Study Protocol: Amendment 1 (PDF, 2020-02-07)
• Statistical Analysis Plan: Version 1 PBRS (PDF, 2022-10-25)
• Statistical Analysis Plan: Version 1 StatKing (PDF, 2021-10-15)
• Statistical Analysis Plan: version 2.0 PBRS (PDF, 2023-02-21)

• Renato Mantegazza, MD, Principal investigator, Carlo Besta Neurological Institute