A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of the Safety and Efficacy of Dexpramipexole in Subjects With Amyotrophic Lateral Sclerosis
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 942
- Locations
- 82
- Primary Endpoint
- Composite Assessment of Function and Survival (CAFS) at 12 Months
Study Overview
Brief Summary
The purpose of this study is to determine whether dexpramipexole (150 mg twice daily) is safe and effective in the treatment of Amyotrophic Lateral Sclerosis (ALS).
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 determine whether dexpramipexole (150 mg twice daily) is safe and effective in the treatment of ALS.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Aged 18 to 80 years old, inclusive, on Day
- •Diagnosis of sporadic or familial ALS.
- •Onset of first ALS symptoms within 24 months prior to Day
- •World Federation of Neurology El Escorial criteria are met for a possible, laboratory-supported probable, probable, or definite ALS diagnosis.
- •Upright slow vital capacity (SVC) of 65% or more at screening.
- •Patients taking or not taking Riluzole are eligible for this study: if a patient has never taken Riluzole, he or she is eligible; if a patient is currently taking Riluzole, he or she must have been on a stable dose for at least 60 days; if a patient has discontinued Riluzole, he or she must have stopped taking it for at least 30 days.
- •Must be able to swallow tablets at the time of study entry.
Exclusion Criteria
- •Other medically significant illness.
- •Clinically significant abnormal laboratory values.
- •Pregnant women or women breastfeeding.
- •Prior exposure to dexpramipexole.
- •Currently taking pramipexole or other dopamine agonists.
- •Other protocol-defined inclusion/exclusion criteria may apply.
Arms & Interventions
Dexpramipexole
Intervention: Dexpramipexole (Drug)
Placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Composite Assessment of Function and Survival (CAFS) at 12 Months
Time Frame: 12 months
The Composite Assessment of Function and Survival (CAFS) is a between-group comparison of a single ranked clinical outcome based on (1) the change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) score and (2) time to death. Each subject is ranked according to time-to-death (earlier deaths ranked lower than later deaths). Subjects who survive are ranked more favorably than subjects who died. Among the survivors, subjects are ranked according to change in ALSFRS-R (greater worsening of ALSFRS-R is ranked lower than less worsening or an improvement in ALSFRS-R). The ranked scores range from 001 to 941 (the number of subjects in the Efficacy Population) with larger rank score numbers associated with a better outcome. The ranks were analyzed using an ANCOVA model, which includes treatment as a fixed effect and adjusts for baseline ALSFRS-R score, duration of symptoms, site of onset, and use of riluzole. The least square mean rank score is presented for each treatment group.
Death up to 12 Months (CAFs Individual Component)
Time Frame: 12 months
The longest duration of follow-up for this time to the death analysis was 12 months. In the study, subjects were followed for 12-18 months.
Change From Baseline in ALSFRS-R at 12 Months (CAFs Individual Component)
Time Frame: 12 months
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 of 48, with higher scores representing better function.
Secondary Outcomes
- Death or Respiratory Insufficiency (DRI) up to Month 18(18 months)
- Death up to 18 Months(18 months)
- ≤50% Predicted Upright Slow Vital Capacity (SVC) or Died up to 18 Months(18 months)