Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS, Motor Neuron Disease, Amyotrophic Lateral Sclerosis
Brief summary
The purpose of the study is to collect long-term safety data from subjects with Amyotrophic Lateral Sclerosis (ALS) exposed to dexpramipexole.
Detailed description
Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive, degenerative disease of motor neurons in the brain and spinal cord that leads to muscle atrophy and spasticity in limb and bulbar muscles resulting in weakness and loss of ambulation, oropharyngeal dysfunction, weight loss, and ultimately respiratory failure. The purpose of this study is to collect long-term safety data from subjects with Amyotrophic Lateral Sclerosis (ALS) exposed to dexpramipexole.
Interventions
DRUGDexpramipexole
Oral tablet 150 mg given twice daily (BID)
Sponsors
Biogen
Knopp Biosciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subject has the ability to understand the purpose and risks of the study and provide signed and dated informed consent (or have the consent confirmed by a witness if unable to write) and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. * Subject was enrolled in either CL211 (NCT00931944) or Study 223AS302 (NCTO1281189). * Subject has completed their last visit in Study CL211 (NCT00931944) or Study 223AS302 (NCTO1281189). * Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 1 month (females) or 3 months (males) after their last dose of study treatment.
Exclusion criteria
* Subject withdrew prematurely from Study CL211 (NCT00931944) or Study 223AS302 (NCTO1281189). * Subject permanently discontinued study treatment in Study CL211 (NCT00931944) or Study 223AS302 (NCTO1281189) for any reason other than enrollment into this study. * Subject from Study CL211 (NCT00931944) or Study 223AS302 (NCTO1281189) has a significant change in medical history (including laboratory tests or a clinically significant condition) that in the opinion of the Investigator would impair the subject's medical fitness for participation and preclude treatment. * Female subject who is pregnant or breastfeeding. * Subject is currently enrolled in any investigational drug study other than Study CL211 (NCT00931944) or Study 223AS302 (NCTO1281189). * Subject is taking pramipexole, other dopamine agonists, any other agent with dopaminergic activity, or any other disallowed concomitant medication. * Subject is unwilling or unable to comply with the requirements of the protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the protocol. At a minimum, subjects who are not able to travel to the study site must be willing to agree to remote blood draws for clinical laboratory evaluations and telephone visits to report Adverse Events, concomitant medications, and Amyotrophic Lateral Sclerosis Functional Rating Scale (revised) (ALSFRS-R) scores.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Potentially Clinically Significant ECG Results | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | Number of Participants with Potentially Clinically Significant ECG Results. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test. |
| Number of Subjects Who Discontinued the Study Treatment Due to an Adverse Event | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | The number of subjects enrolled who discontinued the study treatment due to an adverse event during the study |
| Number of Participants With Potentially Clinically Significant Vital Sign Results | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | Number of Participants with Potentially Clinically Significant Vital Sign Abnormalities. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test. |
| Number of Participants With Potentially Clinically Significant Hematology Results | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | Number of Participants with Potentially Clinically Significant Hematology Results. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test. |
| Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | Number of Participants with Potentially Clinically Significant Blood Chemistry Results. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test. |
| Number of Subjects Who Reported an Adverse Event | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | The number of subjects who reported an adverse event during the study |
| Number of Subjects Who Experienced a Serious Adverse Event | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | The number of subjects enrolled who reported a serious adverse event during the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Slope of Sniff Nasal Inspiratory Pressure (SNIP) From Baseline to End of Study | Up to maximum 226 days: approximately 32.2 weeks | SNIP is a test of inspiratory force (sternocleidomastoid and diaphragm) measured via a nasal cannula and is used to assess respiratory muscle weakness and to monitor changes in respiratory muscle strength over time. During the SNIP maneuver, the patient is asked to perform a strong, sharp, maximal sniff, whereby nasal pressure is measured via nasal cannula. The maximum recorded value after several attempts, with rest in between attempts, was use in the analysis. |
| Death up to 6 Months | 6 Months | Kaplan-Meier estimate of percentage of subjects who died up to 6 months |
| Percentage of Participants With Death or Death Equivalent up to 6 Months | 6 months | Kaplan-Meier estimate of percentage of subjects who died or had a death equivalent event (tracheostomy or permanent assisted ventilation \[PAV\], defined as use of noninvasive ventilation \[NIV\] for ≥22 hours per day for ≥10 days) up to 6 months |
| Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to End of Study | Up to maximum 226 days: approximately 32.2 weeks | The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score between 0 to 48, with higher scores representing better function. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis ALSFRS-R score. Units for slope are change per month in units on the ALSFRS-R scale. |
Countries
Australia, Belgium, Canada, France, Germany, Ireland, Netherlands, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dexpramipexole 150 mg BID Dexpramipexole: Oral tablet 150 mg given twice daily up to 36 months | 616 |
| Total | 616 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 20 |
| Overall Study | Death | 53 |
| Overall Study | Investigator Decision | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | STUDY TERMINATED EARLY BY SPONSOR | 521 |
| Overall Study | Withdrawal by Subject | 20 |
Baseline characteristics
| Characteristic | Dexpramipexole 150 mg BID |
|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 11.48 |
| Age, Customized <50 years | 164 Participants |
| Age, Customized >65 years | 146 Participants |
| Age, Customized between 50-65 years | 305 Participants |
| Age, Customized missing | 1 Participants |
| Body mass index (kg/m^2) | 24.65 kg/m^2 STANDARD_DEVIATION 5.058 |
| Height (cm) | 173.1 cm STANDARD_DEVIATION 9.59 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 6 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 | 19 Participants |
| Race (NIH/OMB) White | 585 Participants |
| Region of Enrollment Australia | 26 participants |
| Region of Enrollment Belgium | 21 participants |
| Region of Enrollment Canada | 39 participants |
| Region of Enrollment France | 33 participants |
| Region of Enrollment Germany | 76 participants |
| Region of Enrollment Ireland | 14 participants |
| Region of Enrollment Netherlands | 26 participants |
| Region of Enrollment Spain | 44 participants |
| Region of Enrollment Sweden | 13 participants |
| Region of Enrollment United Kingdom | 45 participants |
| Region of Enrollment United States | 279 participants |
| Sex: Female, Male Female | 206 Participants |
| Sex: Female, Male Male | 410 Participants |
| Weight (kg) | 73.94 kg STANDARD_DEVIATION 16.528 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 73 / 616 |
| other Total, other adverse events | 215 / 616 |
| serious Total, serious adverse events | 152 / 616 |
Outcome results
Primary
Number of Participants With Potentially Clinically Significant Blood Chemistry Results
Number of Participants with Potentially Clinically Significant Blood Chemistry Results. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Population: The analysis population includes all subjects who received at least one dose of study drug and who had an evaluable post-baseline blood chemistry assessment during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Sodium <= 126 mmol/L | 5 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Sodium >= 156 mmol/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Potassium <= 3 mmol/L | 1 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Potassium >= 6 mmol/L | 4 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Chloride <= 90 mmol/L | 9 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Chloride >= 118 mmol/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Bicarbonate <= 16 mmol/L | 7 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Bicarbonate >= 35 mmol/L | 6 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Calcium <= 2 mmol/L | 7 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Calcium >= 3 mmol/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Magnesium <= 0.5 mmol/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Magnesium >= 1.2 mmol/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Phosphorus <= 0.6 mmol/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Phosphorus >= 1.7 mmol/L | 9 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Aspartate Aminotransferase - SGOT >= 3 x ULN U/L | 4 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Alanine Aminotransferase - SGPT >= 3 x ULN U/L | 12 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Alkaline Phosphatase >= 1.5 x ULN U/L | 4 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Creatinine - Females >= 176.8 umol/L | 1 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Creatinine - Males >= 176.8 umol/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Blood Urea Nitrogen >= 10.7 mmol/L | 23 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Total Bilirubin >= 1.5 x ULN umol/L | 8 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Total Protein <= 45 g/L | 1 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Total Protein >= 100 g/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Albumin <= 25 g/L | 3 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Uric Acid - Females >= 506 umol/L | 1 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Uric Acid - Males >= 625 umol/L | 4 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Glucose <= 2.2 mmol/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Glucose >= 9.7 mmol/L | 43 Participants |
Primary
Number of Participants With Potentially Clinically Significant ECG Results
Number of Participants with Potentially Clinically Significant ECG Results. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Population: The analysis population includes all subjects who received at least one dose of study drug and who had an evaluable post-baseline ECG assessment during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QTcF > 450 ms | 2 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QTcF > 480 ms | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QTcF > 500 ms | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QTcF Change from Baseline > 30 ms | 34 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QTcF Change from Baseline > 60 ms | 3 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QT > 450 ms | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QT > 480 ms | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QT > 500 ms | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QT Change from Baseline > 30 ms | 59 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QT Change from Baseline > 60 ms | 2 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QTcB > 480 ms | 9 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QTcB > 450 ms | 2 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QTcB > 500 ms | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QTcB Change from Baseline > 30 ms | 69 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QTcB Change from Baseline > 60 ms | 6 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | PR > 220 ms and Percent Increase from Baseline >25% | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant ECG Results | QRS > 110 ms and Percent Increase from Baseline >25% | 1 Participants |
Primary
Number of Participants With Potentially Clinically Significant Hematology Results
Number of Participants with Potentially Clinically Significant Hematology Results. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Population: The analysis population includes all subjects who received at least one dose of study drug and who had an evaluable post-baseline hematology assessment during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | White Blood Cell Count < 3.0 x10^9 cells/L | 18 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | White Blood Cell Count >= 16 x10^9 cells/L | 6 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Total Absolute Neutrophil Count < 1.5 x10^9 cells/L | 14 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Total Absolute Neutrophil Count >= 13.5 x10^9 cells/L | 6 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Lymphocyte < 0.8 x10^9 cells/L | 65 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Lymphocyte > 12 x10^9 cells/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Monocytes > 2.5 x10^9 cells/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Eosinophils > 1.6 x10^9 cells/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Basophils > 1.6 x10^9 cells/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Hemoglobin - Females <= 95 g/L | 1 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Hemoglobin - Females >= 175 g/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Hemoglobin - Males <= 115 g/L | 13 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Hemoglobin - Males >= 190 g/L | 1 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Hematocrit - Females <= 32% | 8 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Hematocrit - Females >= 54% | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Hematocrit - Males <= 37% | 47 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Hematocrit - Males >= 60% | 1 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Red Blood Cell Count <= 3.5 x10^12 cells/L | 15 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Red Blood Cell Count >= 6.4 x10^12 cells/L | 3 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Platelet Count <= 75 x10^9 cells/L | 0 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Hematology Results | Platelet Count >= 700 x10^9 cells/L | 3 Participants |
Primary
Number of Participants With Potentially Clinically Significant Vital Sign Results
Number of Participants with Potentially Clinically Significant Vital Sign Abnormalities. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Population: The analysis population includes all subjects who received at least one dose of study drug and who had an evaluable post-baseline vital sign measurement during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Systolic BP >180 mmHg | 2 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Systolic BP Increase from Baseline >40 mmHg | 6 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Systolic BP <90 mmHg | 4 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Systolic BP Decrease from Baseline >30 mmHg | 10 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Diastolic BP >105 mmHg | 20 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Diastolic BP increase from Baseline >30 mmHg | 5 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Diastolic BP <50 mmHg | 2 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Diastolic BP Decrease from Baseline >20 mmHg | 21 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Pulse >120 bpm | 3 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Pulse Increase from Baseline >30 bpm | 16 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Pulse <50 bpm | 2 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Pulse Decrease from Baseline >20 bpm | 30 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Temperature >38.5 C and Increase from Baseline>=1°C | 1 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Weight >=7% Increase from Baseline | 19 Participants |
| Dexpramipexole 150 mg BID | Number of Participants With Potentially Clinically Significant Vital Sign Results | Weight >=7% Decrease from Baseline | 37 Participants |
Primary
Number of Subjects Who Discontinued the Study Treatment Due to an Adverse Event
The number of subjects enrolled who discontinued the study treatment due to an adverse event during the study
Time frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Population: The safety population is defined as all subjects who received at least 1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexpramipexole 150 mg BID | Number of Subjects Who Discontinued the Study Treatment Due to an Adverse Event | 30 Participants |
Primary
Number of Subjects Who Experienced a Serious Adverse Event
The number of subjects enrolled who reported a serious adverse event during the study
Time frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Population: The safety population is defined as all subjects who received at least 1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexpramipexole 150 mg BID | Number of Subjects Who Experienced a Serious Adverse Event | 152 Participants |
Primary
Number of Subjects Who Reported an Adverse Event
The number of subjects who reported an adverse event during the study
Time frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Population: The safety population is defined as all subjects who received at least 1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexpramipexole 150 mg BID | Number of Subjects Who Reported an Adverse Event | 454 Participants |
Secondary
Death up to 6 Months
Kaplan-Meier estimate of percentage of subjects who died up to 6 months
Time frame: 6 Months
Population: Subjects who were randomized, received at least 1 dose of study treatment, had at least 1 available post-dosing efficacy evaluation (ALSFRS-R) or died during the study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexpramipexole 150 mg BID | Death up to 6 Months | 13.95 percentage of participants |
Secondary
Percentage of Participants With Death or Death Equivalent up to 6 Months
Kaplan-Meier estimate of percentage of subjects who died or had a death equivalent event (tracheostomy or permanent assisted ventilation \[PAV\], defined as use of noninvasive ventilation \[NIV\] for ≥22 hours per day for ≥10 days) up to 6 months
Time frame: 6 months
Population: Subjects who were randomized, received at least 1 dose of study treatment, had at least 1 available post-dosing efficacy evaluation (ALSFRS-R) or died during the study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexpramipexole 150 mg BID | Percentage of Participants With Death or Death Equivalent up to 6 Months | 16.35 percentage of participants |
Secondary
Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to End of Study
The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score between 0 to 48, with higher scores representing better function. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis ALSFRS-R score. Units for slope are change per month in units on the ALSFRS-R scale.
Time frame: Up to maximum 226 days: approximately 32.2 weeks
Population: Randomized subjects who had at least 1 post-baseline clinical evaluation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dexpramipexole 150 mg BID | Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to End of Study | -0.7355 Change per month in ALSFRS-R | Standard Error 0.04448 |
Secondary
Slope of Sniff Nasal Inspiratory Pressure (SNIP) From Baseline to End of Study
SNIP is a test of inspiratory force (sternocleidomastoid and diaphragm) measured via a nasal cannula and is used to assess respiratory muscle weakness and to monitor changes in respiratory muscle strength over time. During the SNIP maneuver, the patient is asked to perform a strong, sharp, maximal sniff, whereby nasal pressure is measured via nasal cannula. The maximum recorded value after several attempts, with rest in between attempts, was use in the analysis.
Time frame: Up to maximum 226 days: approximately 32.2 weeks
Population: Randomized subjects who had at least 1 post-baseline clinical evaluation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dexpramipexole 150 mg BID | Slope of Sniff Nasal Inspiratory Pressure (SNIP) From Baseline to End of Study | -0.1895 Change per month in SNIP (in cm H20) | Standard Error 0.09933 |