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Phase 3 Study of Dexpramipexole in ALS (EMPOWER)

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ClinicalTrials.gov Identifier: NCT01281189
Recruitment Status : Completed
First Posted : January 21, 2011
Results First Posted : June 7, 2021
Last Update Posted : June 7, 2021
Sponsor:
Information provided by (Responsible Party):
Knopp Biosciences

Tracking Information
First Submitted Date  ICMJE January 20, 2011
First Posted Date  ICMJE January 21, 2011
Results First Submitted Date  ICMJE December 4, 2020
Results First Posted Date  ICMJE June 7, 2021
Last Update Posted Date June 7, 2021
Study Start Date  ICMJE March 2011
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2021)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 20, 2011)
A joint rank of functional outcomes adjusted for mortality. [ Time Frame: 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2021)
  • Death or Respiratory Insufficiency (DRI) up to Month 18 [ Time Frame: 18 months ]
    Time to Death or Respiratory Insufficiency (DRI) is defined as receipt of a tracheostomy or the use of non-invasive ventilation (NIV) for ≥22 hours per day for at least 10 consecutive days. If NIV is used to meet the criteria for respiratory insufficiency, no measured slow vital capacity (SVC) at any subsequent assessment may be >50%. Time to DRI is calculated from the date of the first dose to the first date of one of the following events: death, tracheostomy, or the 10th day of consecutive NIV with no measured SVC >50% at any subsequent assessment.
  • Death up to 18 Months [ Time Frame: 18 months ]
    Estimated time to death up to 18 months. This includes deaths reported greater than 30 days following discontinuation from the study (the time period for reporting all-cause mortality), regardless of subject disposition, up to 18 months from first dose.
  • ≤50% Predicted Upright Slow Vital Capacity (SVC) or Died up to 18 Months [ Time Frame: 18 months ]
    The date of reaching ≤50% of predicted upright slow vital capacity (SVC) is defined as the date of the first visit at which a predicted upright SVC is ≤50% and continues to remain ≤50% at the subsequent visit except for the last available observation. The time to reach ≤50% of predicted upright SVC is defined as the duration between the date of reaching ≤50% of predicted upright SVC and the date of the first dose of study medication. If the subject is alive and does not reach ≤50% of predicted upright SVC, the time to reach ≤50% of predicted upright SVC will be censored and equal to the number of days from the first dose of study medication until the visit date when the subject's last available SVC assessment is performed. The earliest time (Reaching ≤50% Predicted Upright SVC or death) is used in analysis.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2011)
  • Time to death using all available follow-up data. [ Time Frame: 18 months ]
  • Respiratory decline: time to reach 50% of predicted upright SVC or death. [ Time Frame: 18 months ]
  • 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 ]
  • Change in muscle strength measurements (MSM), as determined by the overall megascore for hand-held dynamometry (HHD) [ Time Frame: 12 months ]
  • Incidence of adverse events, serious adverse events, vital signs, clinical laboratory assessments, physical examination, electrocardiogram tests, and body weight. [ Time Frame: 18 Months ]
  • Population pharmacokinetics. [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Study of Dexpramipexole in ALS
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of the Safety and Efficacy of Dexpramipexole in Subjects With Amyotrophic Lateral Sclerosis
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • Drug: Dexpramipexole
    Oral tablet 150mg twice daily for up to 18 months.
    Other Names:
    • KNS-760704
    • BIIB050
  • Drug: Placebo
    Oral tablet twice daily for up to 18 months.
Study Arms  ICMJE
  • Experimental: Dexpramipexole
    Intervention: Drug: Dexpramipexole
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Cudkowicz ME, van den Berg LH, Shefner JM, Mitsumoto H, Mora JS, Ludolph A, Hardiman O, Bozik ME, Ingersoll EW, Archibald D, Meyers AL, Dong Y, Farwell WR, Kerr DA; EMPOWER investigators. Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial. Lancet Neurol. 2013 Nov;12(11):1059-67. doi: 10.1016/S1474-4422(13)70221-7. Epub 2013 Sep 23. Erratum in: Lancet Neurol. 2013 Nov;12(11):1042. Carbonell, J G [corrected to Gamez, J].

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 10, 2021)
942
Original Estimated Enrollment  ICMJE
 (submitted: January 20, 2011)
804
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Ireland,   Netherlands,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01281189
Other Study ID Numbers  ICMJE 223AS302
EUDRA CT NO: 2010-022818-19
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Knopp Biosciences
Study Sponsor  ICMJE Knopp Biosciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Merit Cudkowicz, MD, MSc Professor of Neurology of the Harvard Medical School
PRS Account Knopp Biosciences
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP