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Amifampridine Phosphate for the Treatment of Congenital Myasthenic Syndromes

This study is currently recruiting participants.
Verified June 2017 by Catalyst Pharmaceuticals, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02562066
First Posted: September 29, 2015
Last Update Posted: June 5, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Catalyst Pharmaceuticals, Inc.
  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.

Condition Intervention Phase
Myasthenic Syndromes, Congenital Drug: amifampridine phosphate Drug: Placebo Phase 3

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Catalyst Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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) ]

Estimated Enrollment: 20
Study Start Date: January 2016
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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.
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.

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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02562066


Contacts
Contact: Gary Ingenito, M.D., Ph.D Tel: +1 305-420-3200 ext 123 gingenito@catalystpharma.com

Locations
United States, California
UCLA Department of Neurology Recruiting
Los Angeles, California, United States, 90095
Contact: Angela Ho    310-825-3264    alho@mednet.ucla.edu   
Principal Investigator: Perry Shieh, MD, PhD         
United States, Georgia
Children's Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30342
Contact: Schauna Gillam    404-785-8299    schauna.gillam@choa.org   
Contact: Sumit Verma, MD    404-785-4688    sumit.verma@emory.edu   
United States, Maryland
Johns Hopkins Pediatric Neurology Recruiting
Baltimore, Maryland, United States, 21287
Contact: Robin Worrell-Thorne    443-287-6294    rworrel1@jhmi.edu   
Principal Investigator: Thomas Crawford, MD         
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Timothy Harrington    857-218-4677    timothy.harrington@childrens.harvard.edu   
Contact: Grace Ordonez    617-919-7384    grace.ordonez@childrens.harvard.edu   
Principal Investigator: Partha Ghosh, MD         
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Alana Mahley    614-355-2606    alana.mahley@nationwidechildrens.org   
Principal Investigator: Samiah Al-Zaidy, MD         
Sponsors and Collaborators
Catalyst Pharmaceuticals, Inc.
Investigators
Principal Investigator: Sumit Verma, M.D. Children's Healthcare of Atlanta
Principal Investigator: Thomas Crawford, M.D. Johns Hopkins Pediatric Neurology
  More Information

Responsible Party: Catalyst Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02562066     History of Changes
Other Study ID Numbers: CMS-001
First Submitted: September 24, 2015
First Posted: September 29, 2015
Last Update Posted: June 5, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Syndrome
Lambert-Eaton Myasthenic Syndrome
Myasthenic Syndromes, Congenital
Disease
Pathologic Processes
Paraneoplastic Syndromes, Nervous System
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Paraneoplastic Syndromes
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Junction Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases
Genetic Diseases, Inborn
3,4-diaminopyridine
4-Aminopyridine
Potassium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action