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Lack of measure appropriate data (MG-ADL).
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Evaluate the long-term safety of amifampridine phosphate in patients with MuSK antibody positive and AChR antibody positive 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| amifampridine phosphate | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amifampridine Phosphate | Drug | tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day |
|
| 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 |
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Inclusion Criteria
Individuals who met any of the exclusion criteria in the original protocol or those listed below are not eligible to participate in the study:
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| Name | Affiliation | Role |
|---|---|---|
| Renato Mantegazza, MD | Carlo Besta Neurological Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States | ||
| Univerity of Pennsylvania |
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extension study to MSK-002
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol: Original Protocol | Nov 12, 2017 |
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| Philadelphia |
| Pennsylvania |
| 19104 |
| United States |
| Department of Neuroimmunology and Neuromuscular Diseases Carlo Besta Neurological Institute Via Celoria | Milan | 11-201332 | Italy |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| Weight | Baseline weight not recorded for 4 participants. | Mean | Standard Deviation | Kg |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Count of Participants | Participants | over 39 months |
|
|
|
Study Duration 39 months
Serious classification based on the FDA regulatory definition of a serious AE.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Serious Adverse Event | Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day. | 0 | 63 | 14 | 63 | 58 | 63 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aortic Valve Stenosis | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| small intestinal obstruction | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| corona virus infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| cervical spine stenosis | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Bone Neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Papillary Thyroid Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Myasthenia Gravis | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Myasthenia Gravis Crisis | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| abortion Spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 20.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cataract | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Diplopia | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Vitreous Floaters | Eye disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypoasthesia Oral | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Paresthesia Oral | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment | Does not include SAE |
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| Asthenia | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Corona Virus Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment | Does not include the SAEs |
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| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Onychomycosis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment | Does not Include the SAEs |
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| Sinusitus | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Upper Respiratory Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Hypoasthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Myasthenia Gravis | Nervous system disorders | MedDRA 20.1 | Systematic Assessment | Does not include SAEs |
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| Paraesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Depression | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Insomnia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
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.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gary Ingenito, MD, Chief Medical Officer | Catalyst Pharmaceuticals, Inc. | 3054203200 | gingenito@catalystpharma.com |
| Mar 7, 2024 |
| Prot_000.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 1 | Feb 7, 2020 | Mar 7, 2024 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Version 1 PBRS | Oct 25, 2022 | Mar 7, 2024 | SAP_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Version 1 StatKing | Oct 15, 2021 | Mar 7, 2024 | SAP_003.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: version 2.0 PBRS | Feb 21, 2023 | Mar 7, 2024 | SAP_004.pdf |
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| ID | Term |
|---|---|
| D009157 | Myasthenia Gravis |
| ID | Term |
|---|---|
| D020361 | Paraneoplastic Syndromes, Nervous System |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010257 | Paraneoplastic Syndromes |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D019636 | Neurodegenerative Diseases |
| D020511 | Neuromuscular Junction Diseases |
| D009468 | Neuromuscular Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000077770 | Amifampridine |
| ID | Term |
|---|---|
| D015761 | 4-Aminopyridine |
| D000631 | Aminopyridines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| >=65 years |
|
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
|
| White |
|
| More than one race |
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| Unknown or Not Reported |
|
|