Phase 3 Study of Dexpramipexole in ALS

Amyotrophic Lateral Sclerosis Clinical Trial

— EMPOWER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01281189
• Other study ID #: 223AS302
• Secondary ID: EUDRA CT NO: 201
• Status: Completed
• Phase: Phase 3
• Start date: March 2011
• Est. completion date: November 2012

Study information

• Verified date: May 2021
• Source: Knopp Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 942
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

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

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Calvary Health Care Bethlehem	Melbourne	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	AZ St-Lucas	Gent
Belgium	UZ Leuven	Leuven
Canada	Univ of Calgary / Foothills MC	Calgary	Alberta
Canada	London Health Sciences Centre	London
Canada	CHUM - Hopital Notre Dame	Montreal	Quebec
Canada	Mcgill University	Montreal	Quebec
Canada	Sunnybrook and Women's College and Health Sciences Centre	Toronto
Canada	University of British Columbia	Vancouver
France	CHRU de Lille - Hôpital Roger Salengro	Lille
France	CHU de Limoges - Hôpital Dupuytren	Limoges
France	Centre Hospitalier La Timone	Marseille
France	CHU Gui de Chauliac	Montpellier
France	CHU de Nice - Hôpital de l'Archet 1	Nice
France	Hôpital La Pitié Salpétrière	Paris
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Bergmannsheil Gmbh	Bochum
Germany	Medizinische Hochschule Hannover (MHH)	Hannover
Germany	Universitätsklinikum Jena	Jena
Germany	University of Ulm, RKU	Ulm
Ireland	Beaumont Hospital	Dublin
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	UMC St. Radboud	Nijmegen
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Spain	Hospital Universitario de Bellvitge	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Carlos III	Madrid
Spain	Hospital La Paz	Madrid
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Karolinska Universitetssjukhuset, Solna	Stockholm
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Walton Centre for Neurology & Neurosurgery	Liverpool
United Kingdom	Kings College Hospital NHS Foundation Trust	London
United Kingdom	Newcastle University Hospital - Clinical Ageing Research Unit	Newcastle
United Kingdom	John Radcliffe Hospital	Oxford
United Kingdom	Sheffield Institute for Transnational Neuroscience	Sheffield
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Massachusetts General Hospital	Charlestown	Massachusetts
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Texas Neurology	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	University of California at San Francisco - Fresno	Fresno	California
United States	St. Mary's Health Care	Grand Rapids	Michigan
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Methodist Neurological Institute	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Nevada School of Medicine	Las Vegas	Nevada
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Neurology Associates, P.C.	Lincoln	Nebraska
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Hospital for Special Care	New Britain	Connecticut
United States	Columbia University	New York	New York
United States	University of California, Irvine	Orange	California
United States	ALS Center at Penn	Philadelphia	Pennsylvania
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute - St. Joseph's Hospital	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Providence ALS Center	Portland	Oregon
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	University of California, Davis	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of Texas Health Sciences Center	San Antonio	Texas
United States	California Pacific Medical Center	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	Research Foundation of the State University of New York	Syracuse	New York
United States	University of South Florida Medical Center	Tampa	Florida
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Knopp Biosciences

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Ireland,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	=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