Long Term Safety of Amifampridine Phosphate in Spinal Muscular Atrophy 3 (SMA3)

• ClinicalTrials.gov Identifier: NCT03819660
• Recruitment Status: Enrolling by invitation
• First Posted: January 28, 2019
• Last Update Posted: February 5, 2020
• Sponsor: Catalyst Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Catalyst Pharmaceuticals, Inc.

Study Description

Brief Summary:

A long term safety study of amifampridine phosphate in patients with spinal muscular atrophy (SMA) Type 3.

Condition or disease	Intervention/treatment	Phase
Muscle Atrophy	Drug: Amifampridine Phosphate 10 MG Oral Tablet	Phase 2

Detailed Description:

This open-label, long term safety study is designed to evaluate the safety of amifampridine phosphate in ambulatory patients diagnosed SMA Type 3 over an extended period. The study is planned to include approximately 12 male and female SMA Type 3 patients. The planned duration of participation for each patient may be up to 1 year. Patients must have demonstrated benefit during the initial SMA-001 trial.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open-label, long term safety treatment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long Term Safety Study of Amifampridine Phosphate in Ambulatory Patients With Spinal Muscular Atrophy (SMA) Type 3
• Actual Study Start Date: March 7, 2019
• Estimated Primary Completion Date: December 31, 2020
• Estimated Study Completion Date: April 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: amifampridine phosphate; Oral tablets, 15 to 80 mg per day in divided doses 3 to 4 times a day for up to 18 months.	Drug: Amifampridine Phosphate 10 MG Oral Tablet; Oral tablets

Outcome Measures

Primary Outcome Measures :

1. The number and severity of treatment related adverse events and serious adverse events as assessed by CTCAE v4.0 [ Time Frame: 18 months ]

   Safety analyses will be conducted on the safety population (i.e. all patients who receive at least 1 dose of amifampridine. The safety analysis will be descriptive and will be presented on observed data only.

   All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). The incidence of TEAEs will be summarized by system organ class, preferred term, relationship to treatment, and severity.

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 50 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Individuals eligible to participate in this study must meet all the following inclusion criteria:

1. Participated in the SMA-001 study
2. 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.
3. Female patients of childbearing potential must have a negative pregnancy test (urine human chorionic gonadotropin [HCG] at the end of SMA-001 study); and must practice an effective, reliable contraceptive regimen during the study and for up to 30 days following discontinuation of treatment.
4. 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:

CRITERIA FOR INCLUSION AND EXCLUSION:

Individuals eligible to participate in this study must meet all the following inclusion criteria:

1. Participated in the SMA-001 study
2. 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.
3. Female patients of childbearing potential must have a negative pregnancy test (urine human chorionic gonadotropin [HCG] at the end of SMA-001 study); and must practice an effective, reliable contraceptive regimen during the study and for up to 30 days following discontinuation of treatment.
4. 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:

Individuals who met any of the exclusion criteria in the original protocol or those listed below are not eligible to participate in the study:

1. Epilepsy and currently on medication.
2. Uncontrolled asthma.
3. Concomitant use with sultopride.
4. Concomitant use with medicinal products with a narrow therapeutic window.
5. Concomitant use with medicinal products with a known to cause QTc prolongation.
6. Clinically significant abnormalities in 12 lead ECG, in the opinion of the Investigator.
7. Subjects with congenital QT syndromes.
8. Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study.
9. Intolerable amifampridine-related side effects
10. Treatment with an investigational drug (other than amifampridine) or device while participating in this study.
11. 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.
12. History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s).

Contacts and Locations

Locations

Italy

Neurological Institute Carlo Besta

Milano, Lombardy, Italy, 20133

Sponsors and Collaborators

Catalyst Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Lorenzo Maggi, MD; Carlo Besta Institute, Milan, Italy

More Information

• Responsible Party: Catalyst Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03819660
• Other Study ID Numbers: SMA-002
• First Posted: January 28, 2019
• Last Update Posted: February 5, 2020
• Last Verified: February 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Catalyst Pharmaceuticals, Inc.:

Type 3

Additional relevant MeSH terms:

Muscular Atrophy; Muscular Atrophy, Spinal; Atrophy; Pathological Conditions, Anatomical; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Spinal Cord Diseases; Central Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases; Amifampridine; Neuromuscular Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Potassium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action