Myasthenia Gravis, GeneralizedPhase 3NCT03304054

Study to Evaluate Amifampridine Phosphate in Patients With MuSK-MG

A Phase 3 study testing Amifampridine Phosphate in people with Myasthenia Gravis, Generalized, run by Catalyst Pharmaceuticals, Inc. at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Myasthenia Gravis, Generalized
What is being tested?: Amifampridine Phosphate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 93 participants
Where: 2 sitesUnited States
Study dates: 18 Apr 2018to 15 Mar 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.
Male or female ≥18 years of age.
Positive serologic test for anti-MuSK antibodies or anti-AChR antibodies as confirmed at Screening or by previous antibody test, with report available.
Confirmatory EMG or EMG report.
Myasthenia Gravis Foundation of America (MGFA) Class II to IV at Screening.
MG-ADL score of ≥6 at Screening, with more than 50% of this score attributed to non-ocular items.

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Patients receiving steroids or pyridostigmine should not have any modification of drug regimen during the month before Screening.
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.
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.

Who cannot join

Epilepsy and currently on medication.
Concomitant use of medicinal products with a known potential to cause QTc prolongation.
Patients with long QT syndromes.
History of thymectomy within 12 months before Screening.
An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormalities, in the opinion of the Investigator.
Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study.

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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.
Use of rituximab or other similar biologic medications for immunomodulation within 6 months prior to Screening.
Treatment with an investigational drug (other than amifampridine) or device within 30 days before Screening or while participating in this study.
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.
History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s).

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Cleveland Clinic
Cleveland, Ohio, 44195
Univerity of Pennsylvania
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: A Randomized, Placebo-control, Parallel Group Study to Evaluate the Effect of Amifampridine Phosphate in Patients With MuSK Antibody Positive Myasthenia Gravis, and a Sample of AChR Antibody Positive Myasthenia Gravis Patients

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.

Conditions: Myasthenia Gravis, Generalized
Being tested: Amifampridine Phosphate, Placebo Oral Tablet
Keywords: MuSK antibody positive
Medical subject headings: Myasthenia Gravis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Amifampridine PhosphateDrug
tablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day
Placebo Oral TabletDrug
tablets matching amifampridine phosphate, 3 to 4 times a day

Study groups in NCT03304054
Study group	Role	What they receive
amifamapridine phosphate tablets	Experimental	Not described Receives: Drug: Amifampridine Phosphate
placebo tablets	Placebo comparator	Not described Receives: Drug: Placebo Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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.
Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Apr 201815 Mar 2020

First posted6 Oct 2017
Study start18 Apr 2018
Primary completion31 Jan 2020
Study completion15 Mar 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Myasthenia Gravis, GeneralizedStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 93 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03304054
Sponsor's protocol ID: MSK-002
Status last verified: Jul 2021
First submitted: 28 Sep 2017
Last updated: 12 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 12 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Placebo-control, Parallel Group Study to Evaluate the Effect of Amifampridine Phosphate in Patients With MuSK Antibody Positive Myasthenia Gravis, and a Sample of AChR Antibody Positive Myasthenia Gravis Patients
ClinicalTrials.gov ID: NCT03304054
Acronym / sponsor ID: MSK-002
Conditions: Myasthenia Gravis, Generalized
Keywords: MuSK antibody positive
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 93 participants (actual)
Lead sponsor: Catalyst Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 18 Apr 2018 (actual)
Primary completion: 31 Jan 2020 (actual)
Study completion: 15 Mar 2020 (actual)
First posted: 6 Oct 2017 (actual)
Results: Posted 13 Aug 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
amifamapridine phosphate tablets	Experimental	Drug: Amifampridine Phosphate
placebo tablets	Placebo comparator	Drug: Placebo Oral Tablet

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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.
Male or female ≥18 years of age.
Positive serologic test for anti-MuSK antibodies or anti-AChR antibodies as confirmed at Screening or by previous antibody test, with report available.
Confirmatory EMG or EMG report.
Myasthenia Gravis Foundation of America (MGFA) Class II to IV at Screening.

Key exclusion criteria (11 listed)

Epilepsy and currently on medication.
Concomitant use of medicinal products with a known potential to cause QTc prolongation.
Patients with long QT syndromes.
History of thymectomy within 12 months before Screening.
An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormalities, in the opinion of the Investigator.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Amifampridine Phosphatetablets equivalent to 10mg amifampridine, titrated to an efficacious and tolerable dose, 3 to 4 times a day	Drug	amifamapridine phosphate tablets
Placebo Oral Tablettablets matching amifampridine phosphate, 3 to 4 times a day	Drug	placebo tablets

Primary outcome

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

1 secondary outcome

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

Results and safety

Results posted to the registry on 13 Aug 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Amifampridine Phosphate - MuSK	27	27
Amifampridine Phosphate - AChR-MG	7	7
Placebo - MuSk	28	27
Placebo - AChR-MG	8	8
Amifampridine Phosphate Only - MuSK	17	0
Amifampridine Phosphate Only- AChR-MG	6	0

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

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).. Mean (Standard Deviation). Unit: Score on a Scale

Measure	Amifampridine Phosphate - MuSK n = 27	Placebo - MuSK n = 28	Amifampridine Phosphate - AChR n = 7	Placebo - AChR n = 8
Baseline (Day 0) MG-ADL Total Raw Score	4.96 (2.915)	3.86 (2.103)	6.14 (3.388)	7.00 (4.175)
Post-Baseline(Day 10 or time at which a patient discontinued treatment) MG-ADL Total Raw Score	6.00 (3.658)	6.11 (3.19)	4.71 (3.147)	10.38 (3.583)
CFB MG-ADL Total Score	1.04 (2.980)	2.25 (3.658)	-1.43 (2.225)	3.38 (2.825)

Amifampridine Phosphate - MuSK vs Placebo - MuSK vs Amifampridine Phosphate - AChR vs Placebo - AChR: p = 0.2196, Wilcoxon (Mann-Whitney)

Population analysed: 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.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Amifampridine Phosphate	2 of 86 (2.3%)	80 of 86 (93%)	0 of 86
Placebo	0 of 36 (0%)	7 of 36 (19.4%)	0 of 36
Overall	2 of 86 (2.3%)	80 of 86 (93%)	0 of 86

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Renato Mantegazza, MD principal investigator

Carlo Besta Neurologic Institute

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Amifampridine Phosphate in people with Myasthenia Gravis, Generalized, run by Catalyst Pharmaceuticals, Inc. at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Myasthenia Gravis-Activities of Daily Living (MG-ADL) Summary by Time Point and Myasthenia Gravis Type: Wilcoxon-Mann-Whitney Rank Sum Test Results (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).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03304054.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2024.