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CompletedNCT03304054Updated Mar 12, 2024Results posted

Study to Evaluate Amifampridine Phosphate in Patients With MuSK-MG

A Phase 3 interventional study of Amifampridine Phosphate and Placebo Oral Tablet in Myasthenia Gravis, Generalized, sponsored by Catalyst Pharmaceuticals, Inc.. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-12.

Sponsored by Catalyst Pharmaceuticals, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
93
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Efficacy and safety of amifampridine phosphate in improving the activities of daily living for patients with antibody positive MuSK myasthenia gravis.

Read the detailed description

Randomized, double-blind, placebo-controlled, parallel group study is designed to evaluate the safety, tolerability and efficacy of amifampridine phosphate in patients with MuSK-MG. In addition, a sample of AChR-MG patients will be assess for efficacy and safety of amifampridine phosphate. Planned duration of participation for each patient is at least 38 days, excluding the screening period. Eligible patients will be titrated to an efficacious dose of amifampridine phosphate and those who demonstrate improvement will be randomized to either placebo or amifampridine, in a double-blind fashion, for 10 days.

02

Conditions studied

  • Myasthenia Gravis, Generalized

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Keywords

  • MuSK antibody positive
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. 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.
  2. Male or female ≥18 years of age.
  3. Positive serologic test for anti-MuSK antibodies or anti-AChR antibodies as confirmed at Screening or by previous antibody test, with report available.
  4. Confirmatory EMG or EMG report.
  5. Myasthenia Gravis Foundation of America (MGFA) Class II to IV at Screening.
  6. MG-ADL score of ≥6 at Screening, with more than 50% of this score attributed to non-ocular items.
  7. Patients receiving steroids or pyridostigmine should not have any modification of drug regimen during the month before Screening.
  8. Female patients of childbearing potential must have a negative pregnancy test (serum human chorionic gonadotropin [HCG] at screening); and must practice an effective, reliable contraceptive regimen during the study and for up to 30 days following discontinuation of treatment.
  9. 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.

Exclusion criteria

Exclusion Criteria:

  1. Epilepsy and currently on medication.
  2. Concomitant use of medicinal products with a known potential to cause QTc prolongation.
  3. Patients with long QT syndromes.
  4. History of thymectomy within 12 months before Screening.
  5. An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormalities, in the opinion of the Investigator.
  6. Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study.
  7. Patients receiving immunomodulatory treatment (e.g. plasma exchange [PE], therapeutic plasma exchange [TPE], intravenous immunoglobulin G [IVIG]) should not have any treatment in the previous 4 weeks prior to Randomization or at any time during the study.
  8. Use of rituximab or other similar biologic medications for immunomodulation within 6 months prior to Screening.
  9. Treatment with an investigational drug (other than amifampridine) or device within 30 days before Screening or while participating in this study.
  10. 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.
  11. History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s).
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
93 participants (actual)

Study arms

  • Experimental
    amifamapridine phosphate tablets

    Drug: Amifampridine Phosphate

  • Placebo comparator
    placebo tablets

    Drug: Placebo Oral Tablet

Interventions

  • DrugAmifampridine Phosphate

    tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day

  • DrugPlacebo Oral Tablet

    tablets matching amifampridine phosphate, 3 to 4 times a day

05

What researchers measure

Primary outcomes

  1. Myasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results

    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

    Time frame: 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).

Secondary outcomes

  1. Quantitative Myasthenia Gravis (QMG) Total Score Summary Statistics by Time Point and MG Type: Wilcoxon-Mann-Whitney Rank Sum Test Results

    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.

    Time frame: 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).

06

Results

Posted Aug 13, 2021

Participant flow

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

Participant flow — Overall Study
MilestoneAmifampridine Phosphate - MuSKAmifampridine Phosphate - AChR-MGPlacebo - MuSkPlacebo - AChR-MGAmifampridine Phosphate Only - MuSKAmifampridine Phosphate Only- AChR-MG
Started277288176
Completed27727800
Not completed0010176

Outcome measures

PrimaryMyasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results

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

Time frame:
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).
Reported as:
Mean · Score on a Scale
Myasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results
Score on a ScaleAmifampridine Phosphate - MuSKPlacebo - MuSKAmifampridine Phosphate - AChRPlacebo - AChR
Baseline (Day 0) MG-ADL Total Raw Score4.96 ± 2.9153.86 ± 2.1036.14 ± 3.3887.00 ± 4.175
Post-Baseline(Day 10 or time at which a patient discontinued treatment) MG-ADL Total Raw Score6.00 ± 3.6586.11 ± 3.194.71 ± 3.14710.38 ± 3.583
CFB MG-ADL Total Score1.04 ± 2.9802.25 ± 3.658-1.43 ± 2.2253.38 ± 2.825
Statistical analysis
  • Amifampridine Phosphate - MuSK vs Placebo - MuSK vs Amifampridine Phosphate - AChR vs Placebo - AChR · Wilcoxon (Mann-Whitney) · p = 0.2196 (P-value for Wilcoxon-Mann-Whitney Test of Equality of change from baseline distributions between the amifampridine phosphate and placebo treatment groups.)
SecondaryQuantitative Myasthenia Gravis (QMG) Total Score Summary Statistics by Time Point and MG Type: Wilcoxon-Mann-Whitney Rank Sum Test Results

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.

Time frame:
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).
Reported as:
Mean · Score on a Scale
Quantitative Myasthenia Gravis (QMG) Total Score Summary Statistics by Time Point and MG Type: Wilcoxon-Mann-Whitney Rank Sum Test Results
Score on a ScaleAmifampridine Phosphate - MuSKPlacebo - MuSKAmifampridine Phosphate - AChRPlacebo - AChR
Baseline (Day 0) QMG Total Raw Score10.00 ± 3.8738.64 ± 3.74410.57 ± 3.35914.13 ± 4.155
Post-Baseline (day 10 or time at which a patient discontinued treatment early) QMG Total Raw Score11.19 ± 5.36710.16 ± 3.64810.86 ± 3.02414.43 ± 3.952
CFB QMG Total Score1.19 ± 3.991.80 ± 3.9480.29 ± 3.0390.86 ± 2.673
Statistical analysis
  • Amifampridine Phosphate - MuSK vs Placebo - MuSK vs Amifampridine Phosphate - AChR vs Placebo - AChR · Wilcoxon (Mann-Whitney) · p = 0.3736 (P-value for Wilcoxon-Mann-Whitney Test of Equality of change from baseline distributions between the amifampridine phosphate and placebo treatment groups.)

Adverse events

Collected over 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.. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Amifampridine Phosphate0/86 (0%)2/86 (2.3%)80/86 (93%)
Placebo0/36 (0%)0/36 (0%)7/36 (19.4%)
Overall0/86 (0%)2/86 (2.3%)80/86 (93%)
Most frequent serious events
Most frequent serious events
EventAmifampridine PhosphatePlaceboOverall
Myasthenia gravisNervous system disorders1/860/361/86
Myasthenia gravis crisisNervous system disorders1/860/361/86
Most frequent other events
Showing 10 of 43
Most frequent other events
EventAmifampridine PhosphatePlaceboOverall
Paraesthesia oralGastrointestinal disorders37/860/3637/86
ParaesthesiaNervous system disorders34/860/3634/86
NauseaGastrointestinal disorders14/860/3614/86
DiarrhoeaGastrointestinal disorders12/860/3612/86
FatigueGeneral disorders10/862/3612/86
HeadacheNervous system disorders11/860/3611/86
Hypoaesthesia oralGastrointestinal disorders9/860/369/86
DizzinessNervous system disorders8/860/368/86
Abdominal pain upperGastrointestinal disorders7/860/367/86
DyspepsiaGastrointestinal disorders7/860/367/86

Baseline characteristics

The analysis of baseline characteristics included all patients in the Safety population, who are those patients who enrolled and received at least one dose of amifampridine. Patients who began the run-in period belong to the Safety population whether they were randomized to treatment or not.

Age, Continuous
Age, Continuous(years)Amifampridine PhosphatePlaceboAmifampridine Phosphate OnlyTotal
Mean53.1 ± 14.9253.5 ± 12.6145.9 ± 11.3151.9 ± 13.52
Sex: Female, Male
Sex: Female, Male(Participants)Amifampridine PhosphatePlaceboAmifampridine Phosphate OnlyTotal
Female24281466
Male108220
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Amifampridine PhosphatePlaceboAmifampridine Phosphate OnlyTotal
Hispanic or Latino121518
Not Hispanic or Latino3334168
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Amifampridine PhosphatePlaceboAmifampridine Phosphate OnlyTotal
American Indian or Alaska Native0000
Asian0011
Native Hawaiian or Other Pacific Islander0000
Black or African American3227
White31341378
More than one race0000
Unknown or Not Reported0000
Weight
Weight(kg)Amifampridine PhosphatePlaceboAmifampridine Phosphate OnlyTotal
Mean84.6 ± 21.1184.3 ± 27.2776.1 ± 32.2882.9 ± 25.96
Height
Height(cm)Amifampridine PhosphatePlaceboAmifampridine Phosphate OnlyTotal
Mean164.7 ± 7.64163.5 ± 10.75163.6 ± 7.37164.0 ± 8.99
07

Study locations

2 sites
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • Univerity of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
08

References and documents

Study documents

  • Study protocol · Jun 27, 2017
  • Statistical analysis plan · Jan 27, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03304054
Lead sponsor
Catalyst Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Oct 6, 2017
Start date
Apr 18, 2018
Primary completion
Jan 31, 2020
Completion
Mar 15, 2020
Results posted
Aug 13, 2021
Last update
Mar 12, 2024

Study contacts

Renato Mantegazza, MD
principal investigator · Carlo Besta Neurologic Institute

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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