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

NCT03781479 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SMA-001
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Muscular Atrophy, Spinal

Keywords

Type 3

Outcome Measures

Primary Outcomes (1)

• 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.

  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

Study Arms (2)

Amifampridine Phosphate - Placebo

EXPERIMENTAL

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

Drug: Amifampridine Phosphate; Drug: Placebo Oral Tablet

Placebo - Amifampridine Phosphate

EXPERIMENTAL

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

Drug: Amifampridine Phosphate; Drug: Placebo Oral Tablet

Interventions

Amifampridine Phosphate DRUG

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.

Also known as: 3,4 diaminopyridine phosphate

Amifampridine Phosphate - Placebo; Placebo - Amifampridine Phosphate

Placebo Oral Tablet DRUG

Placebo Oral Tablet

Amifampridine Phosphate - Placebo; Placebo - Amifampridine Phosphate

Eligibility Criteria

• Age: 6 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Catalyst Pharmaceuticals, Inc.: lead

Study Sites (1)

Neurological Institute Carlo Besta

Milan, Lombardy, 20133, Italy

Location

Related Publications (1)

• 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.

  PMID: 35763114 DERIVED

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

Amifampridine

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

4-Aminopyridine; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Gary Ingenito
• Organization: Catalyst Pharmaceuticals, Inc.

gingenito@catalystpharma.com

3054203200

Study Officials

• Lorenzo Maggi, MD

  Carlo Besta Institute, Milan, Italy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 20, 2018
• Study Start: January 21, 2019
• Primary Completion: July 23, 2020
• Study Completion: July 23, 2020
• Last Updated: June 1, 2021
• Results First Posted: June 1, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)