Spinal Muscular Atrophy Type 3
Conditions
Keywords
Type 3
Brief summary
A long term safety study of amifampridine phosphate in patients with spinal muscular atrophy (SMA) Type 3.
Detailed description
This open-label outpatient extension study was designed to evaluate the long-term safety and tolerability of amifampridine in patients diagnosed with SMA Type 3. In addition, the evaluation of the effects of amifampridine on the QoL was performed. The study was planned to enroll those patients who had completed the SMA-001 study and after all final evaluations for that study had been completed, or those who demonstrated benefit after completing the dose titration period but failed to meet the randomization criteria on Day 0 of SMA-001. The duration of participation for each patient was expected to be at least 12 months as patients could continue in the study until amifampridine was approved by Regulatory Agencies or the clinical development of amifampridine was terminated for this indication. In addition to amifampridine, patients continued to receive previous concomitant medications, as needed.
Interventions
DRUGAmifampridine Phosphate 10 MG Oral Tablet
Oral tablets
Sponsors
Catalyst Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, extension study , long term safety and tolerability
Eligibility
Sex/Gender
ALL
Age
6 Years to 50 Years
Healthy volunteers
No
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
Individuals who met any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long-term Safety and Tolerability of Amifampridine | 18 months | Number of subjects with treatment emergent adverse events (TEAE). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Clinical Efficacy of Amifampridine Phosphate Over Time in Patients With SMA Type 3 Based on Changes in Quality of Life (QoL). | Screening to end of study. | Quality of life (QoL): the Individualized Quality of Life for neuromuscular disease (INQoL) or the Pediatric Quality of Life (PEDSQLTM) was used for adult or pediatric patients, respectively. Since there were no pediatric patients, none of the patients completed the PEDSQL. The INQol evaluated weakness, pain, fatigue, double vision, muscle locking, droopy eyelids, swallowing difficulties, activities, social relationships, emotions and body image. Each of these areas were measured in four categories as follows: 1- Incidence (0= No, 1 =Yes), 2-Severity (0= None to 7 = extreme), 3- Impact - (0= None to 6 = extreme) and 4-Importance (0= None to 6 = extreme). The numbers were summative and are input to the QOL calculation, which is a percentage of severity on a scale of 0-100. The mean value was taken across this population. The higher scores were a worse outcome. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Amifampridine Phosphate The dose of amifampridine was based on optimal neuromuscular benefit determined from the Run-in Period from SMA-001 or could be modified as the discretion of the Investigator. The maximum single dose was 20 mg. The dose range for patients 6 to 16 years of age was 15 to 60 mg, and for those 17 years and older the range was from 30 to 80 mg daily.
Amifampridine Phosphate 10 MG Oral Tablet: Oral tablets | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Amifampridine Phosphate |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 34.8 years STANDARD_DEVIATION 11.3 |
| BMI | 22.7 kg/m^2 |
| Height | 171.9 CM |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment Italy | 6 Participants |
| Region of Enrollment Serbia | 7 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 8 Participants |
| Weight | 67.1 Kg |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 5 / 13 |
| serious Total, serious adverse events | 1 / 13 |
Outcome results
Primary
Long-term Safety and Tolerability of Amifampridine
Number of subjects with treatment emergent adverse events (TEAE).
Time frame: 18 months
Population: TEAE = any AE started at or after the first dose of drug for the current Long-Term Study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amifampridine Phosphate | Long-term Safety and Tolerability of Amifampridine | 5 Participants |
Secondary
To Assess the Clinical Efficacy of Amifampridine Phosphate Over Time in Patients With SMA Type 3 Based on Changes in Quality of Life (QoL).
Quality of life (QoL): the Individualized Quality of Life for neuromuscular disease (INQoL) or the Pediatric Quality of Life (PEDSQLTM) was used for adult or pediatric patients, respectively. Since there were no pediatric patients, none of the patients completed the PEDSQL. The INQol evaluated weakness, pain, fatigue, double vision, muscle locking, droopy eyelids, swallowing difficulties, activities, social relationships, emotions and body image. Each of these areas were measured in four categories as follows: 1- Incidence (0= No, 1 =Yes), 2-Severity (0= None to 7 = extreme), 3- Impact - (0= None to 6 = extreme) and 4-Importance (0= None to 6 = extreme). The numbers were summative and are input to the QOL calculation, which is a percentage of severity on a scale of 0-100. The mean value was taken across this population. The higher scores were a worse outcome.
Time frame: Screening to end of study.
Population: 11 patients completed the screening Quality of Life Score and only 9 patients completed the EOS Quality of Life Score .
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amifampridine Phosphate | To Assess the Clinical Efficacy of Amifampridine Phosphate Over Time in Patients With SMA Type 3 Based on Changes in Quality of Life (QoL). | screening | 33.737 score on a scale | Standard Deviation 17.677 |
| Amifampridine Phosphate | To Assess the Clinical Efficacy of Amifampridine Phosphate Over Time in Patients With SMA Type 3 Based on Changes in Quality of Life (QoL). | End of Study | 39.012 score on a scale | Standard Deviation 14.337 |