Phase 3 Study of Dexpramipexole in ALS (EMPOWER)

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of the Safety and Efficacy of Dexpramipexole in Subjects With Amyotrophic Lateral Sclerosis

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).

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Dexpramipexole; Drug: Placebo

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: Interventional
• Enrollment (Actual): 942
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia
      • Prince of Wales Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women'S Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3121
      • Calvary Health Care Bethlehem
• Belgium
  • Gent, Belgium, 9000
    • AZ St-Lucas
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • London, Canada
    • London Health Sciences Centre
  • Toronto, Canada, M4N 3M5
    • Sunnybrook and Women's College and Health Sciences Centre
  • Vancouver, Canada
    • University of British Columbia
  • Alberta
    • Calgary, Alberta, Canada, T2V 1P9
      • Univ of Calgary / Foothills MC
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • McGill University
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre Dame
• France
  • Lille, France, 59037
    • CHRU de Lille - Hôpital Roger Salengro
  • Limoges, France
    • CHU de Limoges - Hôpital Dupuytren
  • Marseille, France
    • Centre Hospitalier La Timone
  • Montpellier, France, 34295
    • CHU Gui de Chauliac
  • Nice, France
    • CHU de Nice - Hôpital de l'Archet 1
  • Paris, France, 75013
    • Hôpital La Pitié Salpêtrière
• Germany
  • Berlin, Germany
    • Charité - Universitätsmedizin Berlin
  • Bochum, Germany
    • Bergmannsheil Gmbh
  • Hannover, Germany
    • Medizinische Hochschule Hannover (MHH)
  • Jena, Germany
    • Universitätsklinikum Jena
  • Ulm, Germany
    • University of Ulm, RKU
• Ireland
  • Dublin, Ireland, Dublin 9
    • Beaumont Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
  • Nijmegen, Netherlands, 6525 GA
    • UMC St. Radboud
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
• Spain
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 8907
    • Hospital Universitario de Bellvitge
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Madrid, Spain
    • Hospital Carlos III
• Sweden
  • Göteborg, Sweden, 41345
    • Sahlgrenska Universitetssjukhuset
  • Stockholm, Sweden, 17176
    • Karolinska Universitetssjukhuset, Solna
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Liverpool, United Kingdom, L9 7LJ
    • Walton Centre for Neurology & Neurosurgery
  • London, United Kingdom, SE5 8AF
    • Kings College Hospital NHS Foundation Trust
  • Newcastle, United Kingdom, NE4 5PL
    • Newcastle University Hospital - Clinical Ageing Research Unit
  • Oxford, United Kingdom
    • John Radcliffe Hospital
  • Sheffield, United Kingdom, S10 2HQ
    • Sheffield Institute for Transnational Neuroscience
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute - St. Joseph's Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Fresno, California, United States, 93701
      • University of California at San Francisco - Fresno
    • Orange, California, United States, 92868
      • University of California, Irvine
    • Sacramento, California, United States, 95817
      • University of California, Davis
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Connecticut
    • New Britain, Connecticut, United States, 06053
      • Hospital for Special Care
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Tampa, Florida, United States, 33612
      • University of South Florida Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Massachusetts General Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • St. Mary's Health Care
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Hennepin County Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Neurology Associates, P.C.
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University of Nevada School of Medicine
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • Syracuse, New York, United States, 12201
      • Research Foundation of the State University of New York
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Medical Center
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence ALS Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19129
      • Drexel University College of Medicine
    • Philadelphia, Pennsylvania, United States, 19107
      • ALS Center at Penn
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75214
      • Texas Neurology
    • Houston, Texas, United States, 77030
      • Methodist Neurological Institute
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Sciences Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral tablet twice daily for up to 18 months.
Experimental: Dexpramipexole	Drug: Dexpramipexole; Oral tablet 150mg twice daily for up to 18 months.; Other Names: KNS-760704; BIIB050

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Assessment of Function and Survival (CAFS) at 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.	12 months
Death up to 12 Months (CAFs Individual Component)	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.	12 months
Change From Baseline in ALSFRS-R at 12 Months (CAFs Individual Component)	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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death or Respiratory Insufficiency (DRI) up to Month 18	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.	18 months
Death up to 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.	18 months
≤50% Predicted Upright Slow Vital Capacity (SVC) or Died up to 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.	18 months

Collaborators and Investigators

• Sponsor: Knopp Biosciences
• Investigators: Principal Investigator: Merit Cudkowicz, MD, MSc, Professor of Neurology of the Harvard Medical School

Publications and helpful links

General 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].

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: January 20, 2011
• First Submitted That Met QC Criteria: January 20, 2011
• First Posted (Estimate): January 21, 2011

Study Record Updates

• Last Update Posted (Actual): June 7, 2021
• Last Update Submitted That Met QC Criteria: May 10, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; ALS; Motor Neuron Disease; Lou Gehrig's disease; Motor Neurone Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: 223AS302; EUDRA CT NO: 2010-022818-19