Myasthenic Syndromes, CongenitalPhase 3NCT02562066
Amifampridine Phosphate for the Treatment of Congenital Myasthenic Syndromes
A Phase 3 study testing amifampridine phosphate in people with Myasthenic Syndromes, Congenital, run by Catalyst Pharmaceuticals, Inc. at 4 sites in United States.
Trial summary
This randomized, double-blind, controlled, outpatient two-period, two-treatment crossover study is designed to evaluate the efficacy and safety of amifampridine phosphate in patients (ages 2 and above) diagnosed with certain genetic subtypes of CMS and demonstrated open label (amifampridine phosphate) or history of… Read more about this study
- Who is it for?
- Ages 2 to 70 years
- Conditions the study is for
- Myasthenic Syndromes, Congenital
- 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
- 20 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2016to Oct 2019
- 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 2 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Individuals eligible to participate in this study must meet all of the following inclusion criteria:
- Patient's or parent 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, or the patient's legal guardian or caregiver with durable power of attorney can provide written informed consent. An assent form must also be signed if in the judgement of the IRB the children are capable of providing assent.
- Male or female age 2 and above.
- Body weight ≥10 kg.
- Genetically-confirmed CMS involving acetylcholine receptor defect, Rapsyn deficiency, MuSK deficiency, Dok-7 deficiency, SYT2 deficiency,SNAP25B deficiency, and fast channel syndrome.
- MFM 20 or 32 score equal or less than 48 or 76, respectively, at Screening.
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- In patients naïve to 3,4-DAP or amifampridine phosphate, improvement of >20% in MFM20 or MFM32 scores after open label period of up titration of dose
- In patients previously stabilized on 3,4-DAP or amifampridine phosphate, history of meaningful improvement in motor function (in opinion of investigator)
- Willingness of patients receiving pyridostigmine, prednisone, albuterol, ephedrine, or fluoxetine to remain on a stable dose of these medications throughout the study interval.
- Female patients of childbearing potential must have a negative pregnancy test (serum human chorionic gonadotropin [HCG] at Screening); and must practice effective, reliable contraceptive regimen during the study.
- 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.
Who cannot join
- Individuals who meet any of the following exclusion criteria are not eligible to participate in the study:
- CMS subtype diagnosis of acetylcholinesterase deficiency, slow-channel syndrome, LRP4 deficiency, and plectin deficiency.
- Cardiac conduction defects on Screening ECG.
- Seizure disorder.
- Abnormal liver function tests at Screening.
- Abnormal kidney function tests at Screening.
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- Abnormal electrolyte values at Screening.
- Pregnancy or breastfeeding at Screening or planning to become pregnant at any time during the study.
- Any systemic bacterial or other infection, which is clinically significant in the opinion of the investigator and has not been treated with appropriate antibiotics.
- Treatment with an investigational drug (other than amifampridine phosphate), device, or biological agent within 30 days before Screening or while participating in this study.
- Any other 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 phosphate excipient(s).
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Johns Hopkins Pediatric Neurology
Baltimore, Maryland, 21287
Boston Children's Hospital
Boston, Massachusetts, 02115
Ohio State University
Columbus, Ohio, 43221
UCLA Department of Neurology
Los Angeles, California, 90095
About this study
Official title: A Phase 3, Double-blind, Outpatient Crossover Study to Evaluate the Efficacy and Safety of Amifampridine Phosphate (3,4 Diaminopyridine Phosphate) in Patients With Congenital Myasthenic Syndromes (CMS)
This randomized, double-blind, controlled, outpatient two-period, two-treatment crossover study is designed to evaluate the efficacy and safety of amifampridine phosphate in patients (ages 2 and above) diagnosed with certain genetic subtypes of CMS and demonstrated open label (amifampridine phosphate) or history of sustained amifampridine benefit from treatment.
Read the detailed description
Each patient will participate in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate is achieved for 7 days. After this phase, blinded treatment effect will be assessed in a randomized fashion of continuation or cessation of drug (Placebo) starting with Period I (duration 7 days). Following experimental Period 1, patients will be returned to the stable dose administered at the end of the open-label run-in period for approximately 2 weeks, followed by cross over treatment in Period 2 dosing for 7 days. After completion of Period 2, patients will be eligible for expanded access with restoration of open-label amifampridine phosphate at the same dose and frequency as established in the run in phase of the study.
- Conditions
- Myasthenic Syndromes, Congenital
- Being tested
- amifampridine phosphate, Placebo
- Medical subject headings
- Myasthenic Syndromes, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
amifampridine phosphateDrug
Also called 3,4 diaminopyridine phosphate, Firdapse™
Amifampridine phosphate tablets 10 mg will be provided in round, white-scored tablets, and containing amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet.
PlaceboDrug
A placebo equivalent will be provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo will be administered consistent with the dose regimen of amifampridine phosphate.
| Study group | Role | What they receive |
|---|---|---|
| amifampridine phosphate -placebo | Experimental | Each patient will participate in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate is achieved for 7 days. After this phase, half of the subjects will be randomized to receive amifampridine in Period I and then crossed over to receive placebo in Period II. Each randomized treatment period is 7 days in duration and is separated by a re-stabilization period of approximately two weeks where the subject will be returned to the stable dose administered at the end of the open-label run-in period. Dosing will be between 20 - 80 mg per day and frequency will be between 2-4 times per day. Receives: Drug: amifampridine phosphate; Drug: Placebo |
| placebo - amifampridine phosphate | Experimental | Each patient will participate in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate is achieved for 7 days. After this phase, half of the subjects will be randomized to receive placebo in Period I and then crossed over to receive amifampridine in Period II. Each randomized treatment period is 7 days in duration and separated by a re-stabilization period of approximately two weeks where the subject will be returned to the stable dose administered at the end of the open-label run-in period. Dosing will be between 20 - 80 mg per day and frequency will be between 2-4 times per day. Receives: Drug: amifampridine phosphate; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subject Global Impression (SGI) Score Summary: Mann-Whitney Main Effects Test Results; SGI Score Mixed Model Analysis
Subject Global Impression (SGI) rates the subject's impression of the effects of the study medication during the preceding week with max score =7 (most satisfied) and min score =1 (least satisfied). It will be completed at D0 (baseline for Study Period 1), D8, D21 (baseline for Study Period 2), and D29. Change from baseline (CFB) will be assessed for Study Period 1 (difference in SGI score from D0 to D8), Study Period 2 (difference in SGI score from D21 to D29) and the change in CFB from Study Period 1 to Study Period 2 (difference between CFB during Study Period 1 and CFB during Study Period 2). A Mann-Whitney-Wilcoxon test for equality of the CFB results in the two treatments in Period 1 and for the equality of the CFB results in the two treatment sequences will be conducted. A mixed effects liner model will be fit with the SGI raw scores as a response and study arm, treatment, period, age group and mutation type as fixed effect terms and patient as a random effect.
Measured: Study Period 1: Baseline (Day 0), Day 8; Study Period 2: Baseline (Day 21), Day 29
Secondary outcomes (2)
Motor Function Measure 32 (MFM-32) Score Summary: Mann-Whitney Main Effect Test Results, MFM-32 Score Mixed Model Analysis
Motor Function Measure 32 (MFM-32) evaluates the severity and progression of motor function in patients 7 years of age or older with max total score = 96 (best score) and min total score =0 (worst score). It will be completed at D0 (baseline for Study Period 1), D8, D21 (baseline for Study Period 2) and D29. CFB will be assessed for Study Period 1 (difference in MFM-32 from D0 to D8), Study Period 2 (difference in MFM-32 from D21 to D28) and the change in CFB from Study Period 1 to Study Period 2 (difference between CFB during Study Period 1 and CFB during Study Period 2). A Mann-Whitney-Wilcoxon test for equality of CFB results in the two treatments in Period 1 and for the equality of the CFB results in the two treatment sequences will be conducted. A mixed effects linear model will be fit to the overall MFM-32 score as the response variable and fixed effect terms for treatment, period, age group, genetic mutation type, and sequence*period and a random effect for patient.
Measured: Study Period 1: Baseline (Day 0), Day 8; Study Period 2: Baseline (Day 21), Day 29
Motor Function Measure 20 (MFM-20) Score Mixed Model Analysis, MFM-20 Score Mixed Model Analysis
Motor Function Measure 20 (MFM-20) evaluates the severity and progression of motor function in patients 2 to 6 years of age with max total score = 60 (best score) and min total score =0 (worst score). It will be completed at D0 (baseline for Study Period 1), D8, D21 (baseline for Study Period 2) and D29. CFB will be assessed for Study Period 1 (difference in MFM-20 from D0 to D8), Study Period 2 (difference in MFM-20 from D21 to D28) and the change in CFB from Study Period 1 to Study Period 2 (difference between CFB during Study Period 1 and CFB during Study Period 2). A Mann-Whitney-Wilcoxon test for equality of CFB results in the two treatments in Period 1 and for the equality of the CFB results in the two treatment sequences will be conducted. A mixed effects linear model will be fit to the overall MFM-32 score as the response variable and fixed effect terms for treatment, period, age group, genetic mutation type, and sequence*period and a random effect for patient.
Measured: Study Period 1: Baseline (Day 0), Day 8; Study Period 2: Baseline (Day 21), Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2015 (estimated)
- Study startJan 2016
- Primary completionAug 2019
- Study completionOct 2019
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 Myasthenic Syndromes, CongenitalStudies 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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catalyst Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Thomas Crawford, M.D., Principal investigator, Johns Hopkins Pediatric Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02562066
- Sponsor's protocol ID
- CMS-001
- Status last verified
- Feb 2021
- First submitted
- 24 Sep 2015
- Last updated
- 2 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Double-blind, Outpatient Crossover Study to Evaluate the Efficacy and Safety of Amifampridine Phosphate (3,4 Diaminopyridine Phosphate) in Patients With Congenital Myasthenic Syndromes (CMS)
- ClinicalTrials.gov ID
- NCT02562066
- Acronym / sponsor ID
- CMS-001
- Conditions
- Myasthenic Syndromes, Congenital
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Catalyst Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2016
- Primary completion
- Aug 2019 (actual)
- Study completion
- Oct 2019 (actual)
- First posted
- 29 Sep 2015 (estimated)
- Results
- Posted 2 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized, double-blind, controlled, outpatient two-period, two-treatment crossover study is designed to evaluate the efficacy and safety of amifampridine phosphate in patients (ages 2 and above) diagnosed with certain genetic subtypes of CMS and demonstrated open label (amifampridine phosphate) or history of sustained amifampridine benefit from treatment.
Detailed description
Each patient will participate in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate is achieved for 7 days. After this phase, blinded treatment effect will be assessed in a randomized fashion of continuation or cessation of drug (Placebo) starting with Period I (duration 7 days). Following experimental Period 1, patients will be returned to the stable dose administered at the end of the open-label run-in period for approximately 2 weeks, followed by cross over treatment in Period 2 dosing for 7 days. After completion of Period 2, patients will be eligible for expanded access with restoration of open-label amifampridine phosphate at the same dose and frequency as established in the run in phase of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| amifampridine phosphate -placebo | Experimental | Drug: amifampridine phosphate, Drug: PlaceboEach patient will participate in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate is achieved for 7 days. After this phase, half of the subjects will be randomized to receive amifampridine in Period I and then crossed over to receive placebo in Period II. Each randomized treatment period is 7 days in duration and is separated by a re-stabilization period of approximately two weeks where the subject will be returned to the stable dose administered at the end of the open-label run-in period. Dosing will be between 20 - 80 mg per day and frequency will be between 2-4 times per day. |
| placebo - amifampridine phosphate | Experimental | Drug: amifampridine phosphate, Drug: PlaceboEach patient will participate in an open-label unblinded drug escalation/treatment run-in phase for up to 4 weeks until stable dose and frequency of amifampridine phosphate is achieved for 7 days. After this phase, half of the subjects will be randomized to receive placebo in Period I and then crossed over to receive amifampridine in Period II. Each randomized treatment period is 7 days in duration and separated by a re-stabilization period of approximately two weeks where the subject will be returned to the stable dose administered at the end of the open-label run-in period. Dosing will be between 20 - 80 mg per day and frequency will be between 2-4 times per day. |
Who may qualify
- Ages
- 2 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Individuals eligible to participate in this study must meet all of the following inclusion criteria:
- Patient's or parent 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, or the patient's legal guardian or caregiver with durable power of attorney can provide written informed consent. An assent form must also be signed if in the judgement of the IRB the children are capable of providing assent.
- Male or female age 2 and above.
- Body weight ≥10 kg.
- Genetically-confirmed CMS involving acetylcholine receptor defect, Rapsyn deficiency, MuSK deficiency, Dok-7 deficiency, SYT2 deficiency,SNAP25B deficiency, and fast channel syndrome.
Key exclusion criteria (12 listed)
- Individuals who meet any of the following exclusion criteria are not eligible to participate in the study:
- CMS subtype diagnosis of acetylcholinesterase deficiency, slow-channel syndrome, LRP4 deficiency, and plectin deficiency.
- Cardiac conduction defects on Screening ECG.
- Seizure disorder.
- Abnormal liver function tests at Screening.
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 phosphateAlso: 3,4 diaminopyridine phosphate, Firdapse™Amifampridine phosphate tablets 10 mg will be provided in round, white-scored tablets, and containing amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet. | Drug | amifampridine phosphate -placebo, placebo - amifampridine phosphate |
| PlaceboA placebo equivalent will be provided as tablets indistinguishable from the amifampridine phosphate tablets. The placebo will be administered consistent with the dose regimen of amifampridine phosphate. | Drug | amifampridine phosphate -placebo, placebo - amifampridine phosphate |
Primary outcome
Subject Global Impression (SGI) Score Summary: Mann-Whitney Main Effects Test Results; SGI Score Mixed Model Analysis
Time frame: Study Period 1: Baseline (Day 0), Day 8; Study Period 2: Baseline (Day 21), Day 29
Subject Global Impression (SGI) rates the subject's impression of the effects of the study medication during the preceding week with max score =7 (most satisfied) and min score =1 (least satisfied). It will be completed at D0 (baseline for Study Period 1), D8, D21 (baseline for Study Period 2), and D29. Change from baseline (CFB) will be assessed for Study Period 1 (difference in SGI score from D0 to D8), Study Period 2 (difference in SGI score from D21 to D29) and the change in CFB from Study Period 1 to Study Period 2 (difference between CFB during Study Period 1 and CFB during Study Period 2). A Mann-Whitney-Wilcoxon test for equality of the CFB results in the two treatments in Period 1 and for the equality of the CFB results in the two treatment sequences will be conducted. A mixed effects liner model will be fit with the SGI raw scores as a response and study arm, treatment, period, age group and mutation type as fixed effect terms and patient as a random effect.
2 secondary outcomes
Motor Function Measure 32 (MFM-32) Score Summary: Mann-Whitney Main Effect Test Results, MFM-32 Score Mixed Model Analysis
Time frame: Study Period 1: Baseline (Day 0), Day 8; Study Period 2: Baseline (Day 21), Day 29
Motor Function Measure 20 (MFM-20) Score Mixed Model Analysis, MFM-20 Score Mixed Model Analysis
Time frame: Study Period 1: Baseline (Day 0), Day 8; Study Period 2: Baseline (Day 21), Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Thomas Crawford, M.D. principal investigator
Johns Hopkins Pediatric Neurology
4 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 Myasthenic Syndromes, Congenital, run by Catalyst Pharmaceuticals, Inc. at 4 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 11 inclusion and 12 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 2 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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. 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 2 Apr 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?
Subject Global Impression (SGI) Score Summary: Mann-Whitney Main Effects Test Results; SGI Score Mixed Model Analysis (time frame: Study Period 1: Baseline (Day 0), Day 8; Study Period 2: Baseline (Day 21), Day 29). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Apr 2021.