Phase 3 Extension Study of Dexpramipexole in ALS (ENVISION)

April 8, 2022 updated by: Knopp Biosciences

An Open-Label, Multicenter, Extension Study to Evaluate the Long-Term Safety and Efficacy of Dexpramipexole (BIIB050) in Subjects With Amyotrophic Lateral Sclerosis

The purpose of the study is to collect long-term safety data from subjects with Amyotrophic Lateral Sclerosis (ALS) exposed to dexpramipexole.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 collect long-term safety data from subjects with Amyotrophic Lateral Sclerosis (ALS) exposed to dexpramipexole.

Study Type

Interventional

Enrollment (Actual)

616

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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
      • 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
        • Universitatsklinikum 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'hebrón
      • 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
    • California
      • Fresno, California, United States, 03721
        • 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, 12207
        • 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, 19102
        • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Subject has the ability to understand the purpose and risks of the study and provide signed and dated informed consent (or have the consent confirmed by a witness if unable to write) and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
  • Subject was enrolled in either CL211 (NCT00931944) or Study 223AS302 (NCTO1281189).
  • Subject has completed their last visit in Study CL211 (NCT00931944) or Study 223AS302 (NCTO1281189).
  • Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 1 month (females) or 3 months (males) after their last dose of study treatment.

Exclusion Criteria:

  • Subject withdrew prematurely from Study CL211 (NCT00931944) or Study 223AS302 (NCTO1281189).
  • Subject permanently discontinued study treatment in Study CL211 (NCT00931944) or Study 223AS302 (NCTO1281189) for any reason other than enrollment into this study.
  • Subject from Study CL211 (NCT00931944) or Study 223AS302 (NCTO1281189) has a significant change in medical history (including laboratory tests or a clinically significant condition) that in the opinion of the Investigator would impair the subject's medical fitness for participation and preclude treatment.
  • Female subject who is pregnant or breastfeeding.
  • Subject is currently enrolled in any investigational drug study other than Study CL211 (NCT00931944) or Study 223AS302 (NCTO1281189).
  • Subject is taking pramipexole, other dopamine agonists, any other agent with dopaminergic activity, or any other disallowed concomitant medication.
  • Subject is unwilling or unable to comply with the requirements of the protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the protocol. At a minimum, subjects who are not able to travel to the study site must be willing to agree to remote blood draws for clinical laboratory evaluations and telephone visits to report Adverse Events, concomitant medications, and Amyotrophic Lateral Sclerosis Functional Rating Scale (revised) (ALSFRS-R) scores.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dexpramipexole
Dexpramipexole open-label
Drug: Dexpramipexole
Oral tablet 150 mg given twice daily (BID)
Other Names:
  • BIIB050

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects Who Reported an Adverse Event
Time Frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
The number of subjects who reported an adverse event during the study
Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Number of Subjects Who Experienced a Serious Adverse Event
Time Frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
The number of subjects enrolled who reported a serious adverse event during the study
Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Number of Subjects Who Discontinued the Study Treatment Due to an Adverse Event
Time Frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
The number of subjects enrolled who discontinued the study treatment due to an adverse event during the study
Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Number of Participants With Potentially Clinically Significant Vital Sign Results
Time Frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Number of Participants with Potentially Clinically Significant Vital Sign Abnormalities. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Number of Participants With Potentially Clinically Significant Hematology Results
Time Frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Number of Participants with Potentially Clinically Significant Hematology Results. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Number of Participants With Potentially Clinically Significant Blood Chemistry Results
Time Frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Number of Participants with Potentially Clinically Significant Blood Chemistry Results. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Number of Participants With Potentially Clinically Significant ECG Results
Time Frame: Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Number of Participants with Potentially Clinically Significant ECG Results. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Baseline through end of study (maximum 226 days: approximately 32.2 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to End of Study
Time Frame: Up to maximum 226 days: approximately 32.2 weeks
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 between 0 to 48, with higher scores representing better function. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis ALSFRS-R score. Units for slope are change per month in units on the ALSFRS-R scale.
Up to maximum 226 days: approximately 32.2 weeks
Slope of Sniff Nasal Inspiratory Pressure (SNIP) From Baseline to End of Study
Time Frame: Up to maximum 226 days: approximately 32.2 weeks
SNIP is a test of inspiratory force (sternocleidomastoid and diaphragm) measured via a nasal cannula and is used to assess respiratory muscle weakness and to monitor changes in respiratory muscle strength over time. During the SNIP maneuver, the patient is asked to perform a strong, sharp, maximal sniff, whereby nasal pressure is measured via nasal cannula. The maximum recorded value after several attempts, with rest in between attempts, was use in the analysis.
Up to maximum 226 days: approximately 32.2 weeks
Death up to 6 Months
Time Frame: 6 Months
Kaplan-Meier estimate of percentage of subjects who died up to 6 months
6 Months
Percentage of Participants With Death or Death Equivalent up to 6 Months
Time Frame: 6 months
Kaplan-Meier estimate of percentage of subjects who died or had a death equivalent event (tracheostomy or permanent assisted ventilation [PAV], defined as use of noninvasive ventilation [NIV] for ≥22 hours per day for ≥10 days) up to 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Knopp Biosciences

Collaborators

Biogen

Investigators

  • Study Chair: Michael Bozik, MD, Knopp Biosciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

February 1, 2013

Study Registration Dates

First Submitted

May 3, 2012

First Submitted That Met QC Criteria

June 14, 2012

First Posted (Estimate)

June 18, 2012

Study Record Updates

Last Update Posted (Actual)

May 3, 2022

Last Update Submitted That Met QC Criteria

April 8, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 223AS304
  • EUDRA CT #: 2011-006119-70

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe