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Amifampridine Phosphate for the Treatment of Congenital Myasthenic Syndromes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02562066
Recruitment Status : Completed
First Posted : September 29, 2015
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
Catalyst Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE September 24, 2015
First Posted Date  ICMJE September 29, 2015
Last Update Posted Date October 28, 2019
Study Start Date  ICMJE January 2016
Actual Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2018)
Change from baseline in the subject global impression (SGI) scale [ Time Frame: Change from baseline in SGI scores at the end of week 5 (end of Period I) and change from baseline in SGI scores at the end of Week 8 (end of Period 2) ]
SGI is a 7-point scale where patient rates their global impression of the effects of study treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: September 25, 2015)
  • Change from baseline in the composite motor function measure (MFM) score [ Time Frame: Change from baseline in MFM scores at the end of week 5 (end of Period I) and change from baseline in MFM scores at at the end of week 8 (end of Period 2) ]
    MFM evaluates the severity and progression of motor function
  • Change from baseline in the subject global impression (SGI) scale [ Time Frame: Change from baseline in SGI scores at the end of week 5 (end of Period I) and change from baseline in SGI scores at the end of Week 8 (end of Period 2) ]
    The CGI score is a 2-part observer-rated instrument that assesses 1) severity of the patient's disease (CGI S) at a given point in time and 2) change from baseline (CGI-I).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2016)
Change from baseline in the Motor Function Measure (MFM) scale [ Time Frame: Change from baseline in MFM scores at the end of week 5 (end of Period I) and at the end of Week 8 (end of Period 2) ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Amifampridine Phosphate for the Treatment of Congenital Myasthenic Syndromes
Official Title  ICMJE 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)
Brief 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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Myasthenic Syndromes, Congenital
Intervention  ICMJE
  • Drug: amifampridine phosphate
    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.
    Other Name: 3,4 diaminopyridine phosphate, Firdapse™
  • Drug: Placebo
    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 Arms  ICMJE
  • Experimental: amifampridine phosphate -placebo
    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.
    Interventions:
    • Drug: amifampridine phosphate
    • Drug: Placebo
  • Experimental: placebo - amifampridine phosphate
    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.
    Interventions:
    • Drug: amifampridine phosphate
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 26, 2016)
20
Original Estimated Enrollment  ICMJE
 (submitted: September 25, 2015)
10
Actual Study Completion Date  ICMJE October 2019
Actual Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Individuals eligible to participate in this study must meet all of the following inclusion criteria:

  1. 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.
  2. Male or female age 2 and above.
  3. Body weight ≥10 kg.
  4. Genetically-confirmed CMS involving acetylcholine receptor defect, Rapsyn deficiency, MuSK deficiency, Dok-7 deficiency, SYT2 deficiency,SNAP25B deficiency, and fast channel syndrome.
  5. MFM 20 or 32 score equal or less than 48 or 76, respectively, at Screening.
  6. 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
  7. In patients previously stabilized on 3,4-DAP or amifampridine phosphate, history of meaningful improvement in motor function (in opinion of investigator)
  8. Willingness of patients receiving pyridostigmine, prednisone, albuterol, ephedrine, or fluoxetine to remain on a stable dose of these medications throughout the study interval.
  9. 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.
  10. 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.

Exclusion Criteria:

Individuals who meet any of the following exclusion criteria are not eligible to participate in the study:

  1. CMS subtype diagnosis of acetylcholinesterase deficiency, slow-channel syndrome, LRP4 deficiency, and plectin deficiency.
  2. Cardiac conduction defects on Screening ECG.
  3. Seizure disorder.
  4. Abnormal liver function tests at Screening.
  5. Abnormal kidney function tests at Screening.
  6. Abnormal electrolyte values at Screening.
  7. Pregnancy or breastfeeding at Screening or planning to become pregnant at any time during the study.
  8. Any systemic bacterial or other infection, which is clinically significant in the opinion of the investigator and has not been treated with appropriate antibiotics.
  9. Treatment with an investigational drug (other than amifampridine phosphate), device, or biological agent within 30 days before Screening or while participating in this study.
  10. 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.
  11. History of drug allergy to any pyridine-containing substances or any amifampridine phosphate excipient(s).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT02562066
Other Study ID Numbers  ICMJE CMS-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Catalyst Pharmaceuticals, Inc.
Study Sponsor  ICMJE Catalyst Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Thomas Crawford, M.D. Johns Hopkins Pediatric Neurology
PRS Account Catalyst Pharmaceuticals, Inc.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP