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

NCT ID: NCT03781479

Last Updated: 2021-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-21
• Study Completion Date: 2020-07-23

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.

Conditions

Muscular Atrophy, Spinal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Amifampridine Phosphate - Placebo

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

Group Type: EXPERIMENTAL

Amifampridine Phosphate

Intervention Type: 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.

Placebo Oral Tablet

Intervention Type: DRUG

Placebo Oral Tablet

Placebo - Amifampridine Phosphate

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

Group Type: EXPERIMENTAL

Amifampridine Phosphate

Intervention Type: 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.

Placebo Oral Tablet

Intervention Type: DRUG

Placebo Oral Tablet

Interventions

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.

Intervention Type: DRUG

Placebo Oral Tablet

Placebo Oral Tablet

Intervention Type: DRUG

Other Intervention Names

3,4 diaminopyridine phosphate

Eligibility Criteria

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).

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Catalyst Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lorenzo Maggi, MD

Role: PRINCIPAL_INVESTIGATOR

Carlo Besta Institute, Milan, Italy

Locations

Neurological Institute Carlo Besta

Milan, Lombardy, Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 35763114 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SMA-001

Identifier Type: -

Identifier Source: org_study_id