Trial Outcomes & Findings for Long Term Safety Study of Amifampridine Phosphate in MuSK-MG (Muscle Specific Tyrosine Kinase Myasthenia Gravis) (NCT NCT03579966)

Last Updated: 2024-05-07

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

63 participants

Primary outcome timeframe

over 39 months

Results posted on

2024-05-07

Participant Flow

extension study to MSK-002

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	63
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	60

Reasons for withdrawal

Reasons for withdrawal
Measure	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
Overall Study Adverse Event	6
Overall Study Lost to Follow-up	4
Overall Study Physician Decision	10
Overall Study Pregnancy	1
Overall Study Withdrawal by Subject	16
Overall Study Study terminated by Sponsor	22
Overall Study Protocol Violation	1

Baseline Characteristics

Baseline weight not recorded for 4 participants.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Amifampridine Phosphate n=63 Participants 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
Age, Categorical <=18 years	0 Participants n=63 Participants
Age, Categorical Between 18 and 65 years	53 Participants n=63 Participants
Age, Categorical >=65 years	10 Participants n=63 Participants
Age, Continuous	53 years STANDARD_DEVIATION 14.08 • n=63 Participants
Sex: Female, Male Female	47 Participants n=63 Participants
Sex: Female, Male Male	16 Participants n=63 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=63 Participants
Race (NIH/OMB) Asian	0 Participants n=63 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=63 Participants
Race (NIH/OMB) Black or African American	4 Participants n=63 Participants
Race (NIH/OMB) White	59 Participants n=63 Participants
Race (NIH/OMB) More than one race	0 Participants n=63 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=63 Participants
Region of Enrollment United States	36 participants n=63 Participants
Region of Enrollment Italy	27 participants n=63 Participants
Weight	85.9 Kg STANDARD_DEVIATION 24.6 • n=59 Participants • Baseline weight not recorded for 4 participants.

PRIMARY outcome

Timeframe: over 39 months

Outcome measures

Outcome measures
Measure	Treatment Emergent Adverse Events n=63 Participants Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day.
Number of Participants With Treatment-Emergent Adverse Events (Safety and Tolerability)	58 Participants

Adverse Events

Serious Adverse Event

Serious events: 14 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Serious Adverse Event n=63 participants at risk Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day.
Cardiac disorders Aortic Valve Stenosis	1.6% 1/63 • Number of events 1 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Gastrointestinal disorders Dysphagia	1.6% 1/63 • Number of events 1 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Gastrointestinal disorders small intestinal obstruction	1.6% 1/63 • Number of events 1 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Gastrointestinal disorders vomiting	1.6% 1/63 • Number of events 1 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations corona virus infection	4.8% 3/63 • Number of events 3 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations Pneumonia	4.8% 3/63 • Number of events 3 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations Staphylococcal infection	1.6% 1/63 • Number of events 1 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Musculoskeletal and connective tissue disorders cervical spine stenosis	1.6% 1/63 • Number of events 1 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone Neoplasm	1.6% 1/63 • Number of events 1 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary Thyroid Cancer	1.6% 1/63 • Number of events 1 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Myasthenia Gravis	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Myasthenia Gravis Crisis	1.6% 1/63 • Number of events 1 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Pregnancy, puerperium and perinatal conditions abortion Spontaneous	1.6% 1/63 • Number of events 1 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.

Other adverse events

Other adverse events
Measure	Serious Adverse Event n=63 participants at risk Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day.
Ear and labyrinth disorders Cataract	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Ear and labyrinth disorders Diplopia	4.8% 3/63 • Number of events 3 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Eye disorders Vitreous Floaters	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Gastrointestinal disorders Abdominal Pain	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Gastrointestinal disorders Abdominal Pain Upper	7.9% 5/63 • Number of events 5 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Gastrointestinal disorders Diarrhea	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Gastrointestinal disorders Hypoasthesia Oral	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Gastrointestinal disorders Nausea	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Gastrointestinal disorders Paresthesia Oral	23.8% 15/63 • Number of events 15 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Gastrointestinal disorders Vomiting	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
General disorders Asthenia	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
General disorders Fatigue	9.5% 6/63 • Number of events 6 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
General disorders Pyrexia	4.8% 3/63 • Number of events 3 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations Bronchitis	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations Corona Virus Infection	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations Nasopharyngitis	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations Onychomycosis	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations Pneumonia	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations Sinusitus	4.8% 3/63 • Number of events 3 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations Upper Respiratory Infection	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Infections and infestations Urinary Tract Infection	9.5% 6/63 • Number of events 6 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Injury, poisoning and procedural complications Contusion	4.8% 3/63 • Number of events 3 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Metabolism and nutrition disorders Hypokalemia	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Musculoskeletal and connective tissue disorders Arthralgia	4.8% 3/63 • Number of events 3 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Musculoskeletal and connective tissue disorders Back Pain	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Musculoskeletal and connective tissue disorders Muscle Spasms	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Musculoskeletal and connective tissue disorders Muscular Weakness	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Musculoskeletal and connective tissue disorders Myalgia	4.8% 3/63 • Number of events 3 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Musculoskeletal and connective tissue disorders Pain in extremity	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Dizziness	6.3% 4/63 • Number of events 4 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Headache	11.1% 7/63 • Number of events 7 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Hypoasthesia	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Myasthenia Gravis	9.5% 6/63 • Number of events 6 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Paraesthesia	22.2% 14/63 • Number of events 14 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Depression	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Insomnia	4.8% 3/63 • Number of events 3 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Respiratory, thoracic and mediastinal disorders Cough	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.8% 3/63 • Number of events 3 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Skin and subcutaneous tissue disorders Alopecia	3.2% 2/63 • Number of events 2 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.
Skin and subcutaneous tissue disorders Rash	4.8% 3/63 • Number of events 3 • Study Duration 39 months Serious classification based on the FDA regulatory definition of a serious AE.

Additional Information

Gary Ingenito, MD, Chief Medical Officer

Catalyst Pharmaceuticals, Inc.

Phone: 3054203200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place