Trial Outcomes & Findings for Study to Evaluate Amifampridine Phosphate in Patients With MuSK-MG (NCT NCT03304054)

Last Updated: 2024-03-12

Results Overview

Myasthenia Gravis-Activities of Daily Living (MG-ADL) is a self-report scale to assess the patient's MG symptoms and functional performance of activities of daily living. The eight items are scored on a scale of 0-3 with 3 representing the most severe symptoms or impaired performance and 0 representing no symptoms or impaired performance. Each item was assessed by the patient at the last day (Day 0) of the Run-in period and at the post-treatment visit. The post-treatment result will be the result obtained on Day 10. If the patient discontinued treatment early, the post-treatment result may be obtained at an earlier time point. The total MG-ADL score was calculated as the sum of each item score, with a maximum score of 24 (most severe symptoms/impairment) and minimum score of 0 (least severe symptoms/impairment). The change from baseline (CFB) at Day 10 was assessed. A Wilcoxon-Mann-Whitney Rank Sum Test of equality of change from baseline distributions between subjects diagnos

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

93 participants

Primary outcome timeframe

Last day (Day 0) of the Run-in period and at the post-treatment visit (i.e., day 10 or the time point at which a patient discontinued treatment early).

Results posted on

2024-03-12

Participant Flow

The study was conducted from 18 April 2018 - 24 April 2020 at 26 sites in the United States and Europe.

A screening visit was conducted to ensure that each patient met inclusion/exclusion criteria. Those patients successfully completing screening had procedures/assessments conducted at the start of the Run-in period (Day 1, before starting study medication) and during run-in, until stable dose and frequency of amifampridine is established for at least 7 days, and at least a 2-point improvement in MG-ADL score was achieved from the start of Run-in to be eligible for randomization (Day 0).

Participant milestones

Participant milestones
Measure	Amifampridine Phosphate - MuSK Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day MuSK - patients diagnosed with MuSK-MG	Amifampridine Phosphate - AChR-MG Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day AChR-MG- patients diagnosed with AChR-MG	Placebo - MuSk Placebo Oral Tablet: tablets matching amifampridine phosphate, 3 to 4 times a day MuSK - patients diagnosed with MuSK-MG	Placebo - AChR-MG Placebo Oral Tablet: tablets matching amifampridine phosphate, 3 to 4 times a day AChR-MG- patients diagnosed with AChR-MG	Amifampridine Phosphate Only - MuSK Patients receiving amifampridine during the open-label run-in period but were not randomized for the crossover portion of the study and diagnosed with MuSK-MG.	Amifampridine Phosphate Only- AChR-MG Patients receiving amifampridine during the open-label run-in period but were not randomized for the crossover portion of the study and diagnosed with AChR-MG.
Overall Study STARTED	27	7	28	8	17	6
Overall Study COMPLETED	27	7	27	8	0	0
Overall Study NOT COMPLETED	0	0	1	0	17	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Evaluate Amifampridine Phosphate in Patients With MuSK-MG

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Amifampridine Phosphate n=34 Participants Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day	Placebo n=36 Participants Placebo Oral Tablet: tablets matching amifampridine phosphate, 3 to 4 times a day	Amifampridine Phosphate Only n=16 Participants Patients receiving Amifampridine during the open-label Run-in period but were not randomized for the crossover portion of the study.	Total n=86 Participants Total of all reporting groups
Age, Continuous	53.1 years STANDARD_DEVIATION 14.92 • n=5 Participants	53.5 years STANDARD_DEVIATION 12.61 • n=7 Participants	45.9 years STANDARD_DEVIATION 11.31 • n=5 Participants	51.9 years STANDARD_DEVIATION 13.52 • n=4 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	28 Participants n=7 Participants	14 Participants n=5 Participants	66 Participants n=4 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	20 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	15 Participants n=5 Participants	18 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants	34 Participants n=7 Participants	1 Participants n=5 Participants	68 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	34 Participants n=7 Participants	13 Participants n=5 Participants	78 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Weight	84.6 kg STANDARD_DEVIATION 21.11 • n=5 Participants	84.3 kg STANDARD_DEVIATION 27.27 • n=7 Participants	76.1 kg STANDARD_DEVIATION 32.28 • n=5 Participants	82.9 kg STANDARD_DEVIATION 25.96 • n=4 Participants
Height	164.7 cm STANDARD_DEVIATION 7.64 • n=5 Participants	163.5 cm STANDARD_DEVIATION 10.75 • n=7 Participants	163.6 cm STANDARD_DEVIATION 7.37 • n=5 Participants	164.0 cm STANDARD_DEVIATION 8.99 • n=4 Participants

PRIMARY outcome

Timeframe: Last day (Day 0) of the Run-in period and at the post-treatment visit (i.e., day 10 or the time point at which a patient discontinued treatment early).

Population: The analysis of primary outcome data was based on the Full Analysis Set population, which included all randomized patients who received at least one dose of study medication (amifampridine or placebo post randomization) and had at least one post-treatment efficacy assessment. Patients who discontinued with no post-randomization data (no Day 0 and no Day 10 data) were excluded from all efficacy analyses but were included in the safety analyses.

Outcome measures

Outcome measures
Measure	Amifampridine Phosphate - MuSK n=27 Participants Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day Patients randomized to receive Amifampridine and diagnosed with MuSK-MG.	Placebo - MuSK n=28 Participants Placebo Oral Tablet: tablets matching amifampridine phosphate, 3 to 4 times a day Patients randomized to receive Placebo and diagnosed with MuSK-MG.	Amifampridine Phosphate - AChR n=7 Participants Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day Patients randomized to receive Amifampridine and diagnosed with AChR-MG.	Placebo - AChR n=8 Participants Placebo Oral Tablet: tablets matching amifampridine phosphate, 3 to 4 times a day Patients randomized to receive Placebo and diagnosed with AChR-MG.
Myasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results Baseline (Day 0) MG-ADL Total Raw Score	4.96 Score on a Scale Standard Deviation 2.915	3.86 Score on a Scale Standard Deviation 2.103	6.14 Score on a Scale Standard Deviation 3.388	7.00 Score on a Scale Standard Deviation 4.175
Myasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results Post-Baseline(Day 10 or time at which a patient discontinued treatment) MG-ADL Total Raw Score	6.00 Score on a Scale Standard Deviation 3.658	6.11 Score on a Scale Standard Deviation 3.19	4.71 Score on a Scale Standard Deviation 3.147	10.38 Score on a Scale Standard Deviation 3.583
Myasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results CFB MG-ADL Total Score	1.04 Score on a Scale Standard Deviation 2.980	2.25 Score on a Scale Standard Deviation 3.658	-1.43 Score on a Scale Standard Deviation 2.225	3.38 Score on a Scale Standard Deviation 2.825

SECONDARY outcome

Timeframe: Last day (Day 0) of the Run-in period and at the post-treatment visit (i.e., day 10 or the time at which a patient discontinued treatment early).

Population: The analysis of secondary outcome data was based on the Full Analysis Set population, which included all randomized patients who received at least one dose of study medication (amifampridine or placebo post randomization) and had at least one post-treatment efficacy assessment. Patients who discontinued with no post-randomization data (no Day 0 and no Day 10 data) were excluded from all efficacy analyses but were included in the safety analyses.

Quantitative Myasthenia Gravis (QMG) assesses the patient's general body strength and fatigability. Each test item is scored on a scale of 0-3 with 3 representing the most severe symptom results and 0 representing no symptom results. Each item was assessed by the patient at Screening, the first (Day 1) and last day (Day 0) of the Run-in period and at the post-treatment visit. The post-treatment result will be the result obtained on Day 10. If the patient discontinued treatment early, the post-treatment result may be obtained at an earlier time point. The total QMG score was calculated as the sum of each item score, with a maximum score of 39 (most severe symptoms) and minimum score of 0 (least severe symptoms). The change from baseline (CFB) at Day 10 was assessed. A Wilcoxon-Mann-Whitney Rank Sum Test of equality of change from baseline distributions between subjects diagnosed with MuSK-MG treated with amifampridine and placebo was conducted.

Outcome measures

Outcome measures
Measure	Amifampridine Phosphate - MuSK n=27 Participants Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day Patients randomized to receive Amifampridine and diagnosed with MuSK-MG.	Placebo - MuSK n=28 Participants Placebo Oral Tablet: tablets matching amifampridine phosphate, 3 to 4 times a day Patients randomized to receive Placebo and diagnosed with MuSK-MG.	Amifampridine Phosphate - AChR n=7 Participants Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day Patients randomized to receive Amifampridine and diagnosed with AChR-MG.	Placebo - AChR n=8 Participants Placebo Oral Tablet: tablets matching amifampridine phosphate, 3 to 4 times a day Patients randomized to receive Placebo and diagnosed with AChR-MG.
Quantitative Myasthenia Gravis (QMG) Total Score Summary Statistics by Time Point and MG Type: Wilcoxon-Mann-Whitney Rank Sum Test Results Baseline (Day 0) QMG Total Raw Score	10.00 Score on a Scale Standard Deviation 3.873	8.64 Score on a Scale Standard Deviation 3.744	10.57 Score on a Scale Standard Deviation 3.359	14.13 Score on a Scale Standard Deviation 4.155
Quantitative Myasthenia Gravis (QMG) Total Score Summary Statistics by Time Point and MG Type: Wilcoxon-Mann-Whitney Rank Sum Test Results Post-Baseline (day 10 or time at which a patient discontinued treatment early) QMG Total Raw Score	11.19 Score on a Scale Standard Deviation 5.367	10.16 Score on a Scale Standard Deviation 3.648	10.86 Score on a Scale Standard Deviation 3.024	14.43 Score on a Scale Standard Deviation 3.952
Quantitative Myasthenia Gravis (QMG) Total Score Summary Statistics by Time Point and MG Type: Wilcoxon-Mann-Whitney Rank Sum Test Results CFB QMG Total Score	1.19 Score on a Scale Standard Deviation 3.99	1.80 Score on a Scale Standard Deviation 3.948	0.29 Score on a Scale Standard Deviation 3.039	0.86 Score on a Scale Standard Deviation 2.673

Adverse Events

Amifampridine Phosphate

Serious events: 2 serious events

Other events: 80 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Overall

Serious events: 2 serious events

Other events: 80 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Amifampridine Phosphate n=86 participants at risk Amifampridine Phosphate: tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day. The AEs reported within this treatment arm are those experienced by all participants who received Amifampridine Phosphate at the time of onset of the AE. Because this study has a run-in period where all subjects received Amifampridine Phosphate, the number of at-risk subjects in this treatment arm is identical to the overall number of at-risk participants. That is, the at-risk count includes those randomized to the Amifampridine Phosphate-Placebo sequence, Placebo - Amifampridine Phosphate sequence and those that received Amifampridine Phosphate during the open-label Run-in period but were not randomized for the crossover portion of the study.	Placebo n=36 participants at risk Placebo Oral Tablet: tablets matching amifampridine phosphate, 3 to 4 times a day The AEs reported within this treatment arm are those experienced by participants who received Placebo at the time of onset of the AE. This includes those randomized to the Placebo - Amifampridine Phosphate sequence.	Overall n=86 participants at risk Includes all participants who received study drug, including Amifampridine Phosphate during the open-label Run-in period or double-blind treatment period or Placebo during the double-blind treatment period.
Nervous system disorders Myasthenia gravis	1.2% 1/86 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continues through four weeks after the last dose or at the early discontinuation visit, for a total of approximately 52 days. Non-serious AEs were recorded for each patient after the first administration of study drug through the last visit or at the early discontinuation visit, for a total of approximately 10 days. Serious classification based on the FDA regulatory definition of a serious AE.	0.00% 0/36 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continues through four weeks after the last dose or at the early discontinuation visit, for a total of approximately 52 days. Non-serious AEs were recorded for each patient after the first administration of study drug through the last visit or at the early discontinuation visit, for a total of approximately 10 days. Serious classification based on the FDA regulatory definition of a serious AE.	1.2% 1/86 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continues through four weeks after the last dose or at the early discontinuation visit, for a total of approximately 52 days. Non-serious AEs were recorded for each patient after the first administration of study drug through the last visit or at the early discontinuation visit, for a total of approximately 10 days. Serious classification based on the FDA regulatory definition of a serious AE.
Nervous system disorders Myasthenia gravis crisis	1.2% 1/86 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continues through four weeks after the last dose or at the early discontinuation visit, for a total of approximately 52 days. Non-serious AEs were recorded for each patient after the first administration of study drug through the last visit or at the early discontinuation visit, for a total of approximately 10 days. Serious classification based on the FDA regulatory definition of a serious AE.	0.00% 0/36 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continues through four weeks after the last dose or at the early discontinuation visit, for a total of approximately 52 days. Non-serious AEs were recorded for each patient after the first administration of study drug through the last visit or at the early discontinuation visit, for a total of approximately 10 days. Serious classification based on the FDA regulatory definition of a serious AE.	1.2% 1/86 • Serious adverse events (SAEs) were recorded for each patient from the time informed consent was obtained at Screening and continues through four weeks after the last dose or at the early discontinuation visit, for a total of approximately 52 days. Non-serious AEs were recorded for each patient after the first administration of study drug through the last visit or at the early discontinuation visit, for a total of approximately 10 days. Serious classification based on the FDA regulatory definition of a serious AE.

Other adverse events

Additional Information

Gary Ingenito

Catalyst Pharmaceuticals, Inc.

Phone: 305-420-3200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place