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

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.

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).