Phase 3 Extension Study of Dexpramipexole in ALS

Study Overview
=================
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.

Official Title
-----------------
An Open-Label, Multicenter, Extension Study to Evaluate the Long-Term Safety and Efficacy of Dexpramipexole (BIIB050) in Subjects With Amyotrophic Lateral Sclerosis

Conditions
-----------------
Amyotrophic Lateral Sclerosis

Intervention / Treatment
-----------------
* Drug: Dexpramipexole


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexpramipexole<br>Dexpramipexole open-label | Drug: Dexpramipexole<br>* Oral tablet 150 mg given twice daily (BID)<br>* Other names: BIIB050;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Reported an Adverse Event | The number of subjects who reported an adverse event during the study | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | 
| Number of Subjects Who Experienced a Serious Adverse Event | The number of subjects enrolled who reported a serious adverse event during the study | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | 
| 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 | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | 
| 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. | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | 
| 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. | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | 
| 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. | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | 
| 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. | Baseline through end of study (maximum 226 days: approximately 32.2 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to maximum 226 days: approximately 32.2 weeks | 
| Death up to 6 Months | Kaplan-Meier estimate of percentage of subjects who died up to 6 months | 6 Months | 
| 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 | 6 months | 
| 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. | Up to maximum 226 days: approximately 32.2 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ALS, Motor Neuron Disease, Amyotrophic Lateral Sclerosis