AChR Myasthenia Gravis, Myasthenia Gravis, MuSK
Conditions
Keywords
Amifampridine Phosphate Amifampridine, 3,4-Diaminopyridine Phosphate, 3,4-Diaminopyridine, 3,4-DAP, Firdapse®, Myasthenia Gravis, MuSK, AChR
Brief summary
Evaluate the long-term safety of amifampridine phosphate in patients with MuSK antibody positive and AChR antibody positive myasthenia gravis.
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.
Interventions
tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day
Sponsors
Catalyst Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Italy, United States
Participant flow
Recruitment details
extension study to MSK-002
Participants by arm
| Arm | Count |
|---|---|
| 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
Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Physician Decision | 10 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Study terminated by Sponsor | 22 |
| Overall Study | Withdrawal by Subject | 16 |
Baseline characteristics
| Characteristic | Amifampridine Phosphate |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants |
| Age, Continuous | 53 years STANDARD_DEVIATION 14.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 59 Participants |
| Region of Enrollment Italy | 27 participants |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 16 Participants |
| Weight | 85.9 Kg STANDARD_DEVIATION 24.6 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 63 |
| other Total, other adverse events | 58 / 63 |
| serious Total, serious adverse events | 14 / 63 |
Outcome results
Primary
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.
Time frame: over 39 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Emergent Adverse Events | Number of Participants With Treatment-Emergent Adverse Events (Safety and Tolerability) | 58 Participants |