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Controlled Trial to Evaluate Amifampridine Phosphate in Spinal Muscular Atrophy Type 3 Patients

Primary Purpose

Muscular Atrophy, Spinal

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Amifampridine Phosphate
Placebo Oral Tablet
Sponsored by
Catalyst Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Muscular Atrophy, Spinal focused on measuring Type 3

Eligibility Criteria

6 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. 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.
  2. Male or female between the ages of 6 and 50 years.
  3. Genetically confirmed diagnosis of SMA Type 3.
  4. Able to walk independently for at least 30 meters.
  5. Not taking Nusinersen for the treatment of SMA (Nusinersen should be stopped at least 6 months before screening). Salbutamol is permitted only if the dose has been stable during the 6 months before screening.
  6. Able to swallow oral medication.
  7. 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.
  8. 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.

Exclusion Criteria:

  1. Epilepsy and currently on medication for epilepsy.
  2. Concomitant use of medicinal products with a known potential to cause QTc prolongation.
  3. Patients with long QT syndromes.
  4. An electrocardiogram (ECG) within 6 months before starting treatment that shows clinically significant abnormalities, in the opinion of the Investigator.
  5. Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study.
  6. Treatment with an investigational drug (other than amifampridine), device, or biological agent within 6 months prior to Screening or while participating in this study.
  7. Surgery for scoliosis or joint contractures within the previous 6 months.
  8. 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.
  9. History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s).
  10. Less than a 3-point improvement in HFSME from start of the Open label Run -in period to end of Run-in (Day 0).

Sites / Locations

  • Neurological Institute Carlo Besta

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Amifampridine Phosphate - Placebo

Placebo - Amifampridine Phosphate

Arm Description

Oral tablets, 30 to 80 mg per day in divided doses 3 to 4 times a day for 4 weeks

Oral tablets, 30 to 80 mg per day in divided doses 3 to 4 times a day for 4 weeks

Outcomes

Primary Outcome Measures

Hammersmith Functional Motor Scale Expanded (HFMSE) Summary Statistics and Mixed Model Analysis
Hammersmith Functional Motor Scale Expanded (HFMSE) assesses motor function by functional item in order of progressive difficulty, with higher values showing higher function abilities. Each item is scored on a scale of 0-2 with 2 representing item achieved unaided and 0 representing inability to achieve item. Each item was assessed by the patient at Screening, the first (Day 1) and last day (Day 0) of the Run-in period, during Period 1 at Day 7 and Day 14, and during Period 2 at Day 21 and Day 28. The total HFMSE score was calculated as the sum of each item score, with a maximum score of 66 (all items achieved unaided) and minimum score of 0 (all items failed). Change from baseline (CFB) will be assessed from Day 0 to Day 28. A mixed effects liner model was fit with the HFMSE change from baseline (CFB) scores at Day 28 as a response and treatment, sequence, and treatment by sequence as fixed effect terms and patient as a random effect.

Secondary Outcome Measures

Full Information

First Posted
December 18, 2018
Last Updated
May 28, 2021
Sponsor
Catalyst Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03781479
Brief Title
Controlled Trial to Evaluate Amifampridine Phosphate in Spinal Muscular Atrophy Type 3 Patients
Official Title
A Randomized, Placebo-Controlled, Crossover Study to Evaluate the Safety and Efficacy of Amifampridine Phosphate in Ambulatory Patients With Spinal Muscular Atrophy (SMA) Type 3
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
January 21, 2019 (Actual)
Primary Completion Date
July 23, 2020 (Actual)
Study Completion Date
July 23, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Catalyst Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A two-period, two-treatment, crossover study to evaluate the safety, tolerability and efficacy of amifampridine phosphate in ambulatory patients diagnosed with spinal muscular atrophy (SMA) Type 3.
Detailed Description
This randomized (1:1), double-blind, placebo-controlled, 2-period, 2-treatment, crossover, outpatient study is designed to evaluate the safety, tolerability and efficacy of amifampridine phosphate in ambulatory patients diagnosed with SMA Type 3. The study is planned to include approximately 12 male and female SMA Type 3 patients. The planned duration of participation for each patient is approximately 2 months, based upon length of dose titration and excluding the screening period, which can last up to 14 days. Patients should only be taking the assigned investigational product (amifampridine phosphate 10 mg tablets or matching placebo tablets), no new therapies are permitted during the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Atrophy, Spinal
Keywords
Type 3

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Amifampridine Phosphate - Placebo
Arm Type
Experimental
Arm Description
Oral tablets, 30 to 80 mg per day in divided doses 3 to 4 times a day for 4 weeks
Arm Title
Placebo - Amifampridine Phosphate
Arm Type
Experimental
Arm Description
Oral tablets, 30 to 80 mg per day in divided doses 3 to 4 times a day for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Amifampridine Phosphate
Other Intervention Name(s)
3,4 diaminopyridine phosphate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Placebo Oral Tablet
Primary Outcome Measure Information:
Title
Hammersmith Functional Motor Scale Expanded (HFMSE) Summary Statistics and Mixed Model Analysis
Description
Hammersmith Functional Motor Scale Expanded (HFMSE) assesses motor function by functional item in order of progressive difficulty, with higher values showing higher function abilities. Each item is scored on a scale of 0-2 with 2 representing item achieved unaided and 0 representing inability to achieve item. Each item was assessed by the patient at Screening, the first (Day 1) and last day (Day 0) of the Run-in period, during Period 1 at Day 7 and Day 14, and during Period 2 at Day 21 and Day 28. The total HFMSE score was calculated as the sum of each item score, with a maximum score of 66 (all items achieved unaided) and minimum score of 0 (all items failed). Change from baseline (CFB) will be assessed from Day 0 to Day 28. A mixed effects liner model was fit with the HFMSE change from baseline (CFB) scores at Day 28 as a response and treatment, sequence, and treatment by sequence as fixed effect terms and patient as a random effect.
Time Frame
Screening, the first (Day 1) and last day (Day 0) of the Run-in period, during Period 1 at Day 7 and Day 14, and during Period 2 at Day 21 and Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 between the ages of 6 and 50 years. Genetically confirmed diagnosis of SMA Type 3. Able to walk independently for at least 30 meters. Not taking Nusinersen for the treatment of SMA (Nusinersen should be stopped at least 6 months before screening). Salbutamol is permitted only if the dose has been stable during the 6 months before screening. Able to swallow oral medication. 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. Exclusion Criteria: Epilepsy and currently on medication for epilepsy. Concomitant use of medicinal products with a known potential to cause QTc prolongation. Patients with long QT syndromes. 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. Treatment with an investigational drug (other than amifampridine), device, or biological agent within 6 months prior to Screening or while participating in this study. Surgery for scoliosis or joint contractures within the previous 6 months. 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). Less than a 3-point improvement in HFSME from start of the Open label Run -in period to end of Run-in (Day 0).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lorenzo Maggi, MD
Organizational Affiliation
Carlo Besta Institute, Milan, Italy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Neurological Institute Carlo Besta
City
Milano
State/Province
Lombardy
ZIP/Postal Code
20133
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35763114
Citation
Bonanno S, Giossi R, Zanin R, Porcelli V, Iannacone C, Baranello G, Ingenito G, Iyadurai S, Stevic Z, Peric S, Maggi L. Amifampridine safety and efficacy in spinal muscular atrophy ambulatory patients: a randomized, placebo-controlled, crossover phase 2 trial. J Neurol. 2022 Nov;269(11):5858-5867. doi: 10.1007/s00415-022-11231-7. Epub 2022 Jun 28.
Results Reference
derived

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Controlled Trial to Evaluate Amifampridine Phosphate in Spinal Muscular Atrophy Type 3 Patients

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