Controlled Trial to Evaluate Amifampridine Phosphate in Spinal Muscular Atrophy Type 3 Patients
Condition: Muscular Atrophy, Spinal
MeSH terms: Muscular Atrophy; Muscular Atrophy, Spinal; Atrophy
Intervention: Amifampridine Phosphate; Placebo Oral Tablet
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.; Placebo Oral Tablet
Intervention MeSH terms: Amifampridine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 13.0
Sex: All
Minimum age: 6 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Type 3

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.
    

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).