Amifampridine Phosphate in Congenital Myasthenic Syndrome (CMS) (EAP-001)

Amifampridine Phosphate in Congenital Myasthenic Syndrome (CMS) (EAP-001)
Recruitment Status: 
Status Last Updated: 
December 9, 2019
Clinical Phenotype(s): 
Study Purpose: 

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.

Drug: amifampridine phosphate
Study 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: 
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)
Study Start Date: 
January 2016
Study Completion Date: 
October 2019
Primary Objective(s): 
  1. 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.
Secondary Objective(s): 
  1. 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) ]
  • Ages Eligible for Study: 2 Years to 70 Years (Child, Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Inclusion Criteria: 
  1. Male or female:
  2. Confirmed genetic diagnosis of CMS.
  3. Negative urine pregnancy test for females of childbearing potential at Screening.
  4. If sexually active and of childbearing potential, willing to use 2 acceptable methods of contraception from screening visit until 3 months after the last dose of investigational product. No adequate clinical data on exposed pregnancies are available for amifampridine. No nonclinical safety data are available regarding the effects of amifampridine on reproductive function. Amifampridine phosphate should not be used during pregnancy. It is unknown whether amifampridine is excreted in human breast milk. The excretion of amifampridine in milk has not been studied in animals. Amifampridine phosphate should not be used during breastfeeding.
  5. 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.
Exclusion Criteria: 
  1. History of epilepsy and on medication/treatment for the same.
  2. CMS subtypes including slow-channel syndrome, LRP4 deficiency, and acetylcholinesterase deficiency.
  3. Current use of dalfampridine (Ampyra®; 4-aminopyridine), and any form of 3,4 DAP other than the investigational product provided, such as amifampridine base and does not agree to discontinue use for the duration of the study.
  4. Use of guanidine hydrochloride within 7 days of starting amifampridine phosphate treatment.
  5. History of drug allergy to any pyridine-containing substances or any amifampridine phosphate excipients (i.e. microcrystalline cellulose, colloidal silicon dioxide or calcium stearate).
  6. Use of any other investigational product (other than 3,4 DAP or amifampridine phosphate) or investigational medical device within 30 days before starting treatment or requirement for any investigational agent before completion of all scheduled study assessments.
  7. An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormality(ies), in the opinion of the patient's personal physician.
  8. Breastfeeding or pregnant or planning to become pregnant (self or partner). Male patients with breastfeeding partners are not excluded from the study.
  9. Any condition that, in the view of the Principal Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.
Study Site(s)/Location(s): 

United States, California

UCLA Department of Neurology

Los Angeles, California 90095

Sponsors & Collaborators: 

Catalyst Pharmaceuticals, Inc.

Principal Investigator(s): 

Perry Shieh, MD, PhD

University of California, Los Angeles ID: