Phase 3 Study of Dexpramipexole in ALS (EMPOWER)

• Time to death or respiratory insufficiency [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• Time to death [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• Respiratory decline: time to reach less than or equal to 50% of predicted upright SVC or death [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• Change in muscle strength measurements (MSM), as determined by the overall megascore for hand-held dynamometry (HHD) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Change in ALS-related health quality, as measured by change in the total score on the Amyotrophic Lateral Sclerosis Assessment Questionnaire-5-Item Form (ALSAQ-5) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Population pharmacokinetics. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• Incidence of adverse events, serious adverse events, vital signs, clinical laboratory assessments, physical examination, electrocardiogram tests, and body weight. [ Time Frame: 18 Months ] [ Designated as safety issue: Yes ]

• Time to death using all available follow-up data. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• Respiratory decline: time to reach 50% of predicted upright SVC or death. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• Change in ALS-related health quality, as measured by change in the total score on the Amyotrophic Lateral Sclerosis Assessment Questionnaire-5-Item Form (ALSAQ-5) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
• Change in muscle strength measurements (MSM), as determined by the overall megascore for hand-held dynamometry (HHD) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Incidence of adverse events, serious adverse events, vital signs, clinical laboratory assessments, physical examination, electrocardiogram tests, and body weight. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
• Population pharmacokinetics. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

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).

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.

• Drug: Dexpramipexole
  Oral tablet 150mg twice daily for up to 18 months.
  Other Name: BIIB050
• Drug: Placebo
  Oral tablet twice daily for up to 18 months.

• Experimental: Dexpramipexole
  Intervention: Drug: Dexpramipexole
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Aged 18 to 80 years old, inclusive, on Day 1.
• Diagnosis of sporadic or familial ALS.
• Onset of first ALS symptoms within 24 months prior to Day 1.
• 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.