Phase 3 Extension Study of Dexpramipexole in ALS
- Registration Number
- NCT01622088
- Lead Sponsor
- Knopp Biosciences
- Brief Summary
The purpose of the study is to collect long-term safety data from subjects with Amyotrophic Lateral Sclerosis (ALS) exposed to dexpramipexole.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 616
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dexpramipexole Dexpramipexole Dexpramipexole open-label
- Primary Outcome Measures
Name Time Method Number of Subjects Who Reported an Adverse Event Baseline through end of study (maximum 226 days: approximately 32.2 weeks) The number of subjects who reported an adverse event during the study
Number of Subjects Who Experienced a Serious Adverse Event 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
Number of Subjects Who Discontinued the Study Treatment Due to an Adverse Event 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
Number of Participants With Potentially Clinically Significant Hematology Results 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.
Number of Participants With Potentially Clinically Significant Blood Chemistry Results 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.
Number of Participants With Potentially Clinically Significant ECG Results 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.
Number of Participants With Potentially Clinically Significant Vital Sign Results 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.
- Secondary Outcome Measures
Name Time Method Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to End of Study 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.
Slope of Sniff Nasal Inspiratory Pressure (SNIP) From Baseline to End of Study 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.
Death up to 6 Months 6 Months Kaplan-Meier estimate of percentage of subjects who died up to 6 months
Percentage of Participants With Death or Death Equivalent up to 6 Months 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
Trial Locations
- Locations (80)
Northwestern University
🇺🇸Chicago, Illinois, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
ALS Center at Penn
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
UMC St. Radboud
🇳🇱Nijmegen, Netherlands
University of Iowa
🇺🇸Iowa City, Iowa, United States
Neurology Associates, P.C.
🇺🇸Lincoln, Nebraska, United States
Emory University
🇺🇸Atlanta, Georgia, United States
University of Ulm, RKU
🇩🇪Ulm, Germany
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Massachusetts General Hospital
🇺🇸Charlestown, Massachusetts, United States
Calvary Health Care Bethlehem
🇦🇺Melbourne, Victoria, Australia
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Centre Hospitalier La Timone
🇫🇷Marseille, France
Research Foundation of the State University of New York
🇺🇸Syracuse, New York, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
AZ St-Lucas
🇧🇪Gent, Belgium
Hôpital La Pitié Salpétrière
🇫🇷Paris, France
Univ of Calgary / Foothills MC
🇨🇦Calgary, Alberta, Canada
University of British Columbia
🇨🇦Vancouver, Canada
CHUM - Hopital Notre Dame
🇨🇦Montreal, Quebec, Canada
CHU Gui de Chauliac
🇫🇷Montpellier, France
Academisch Medisch Centrum
🇳🇱Amsterdam, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Medizinische Hochschule Hannover (MHH)
🇩🇪Hannover, Germany
Texas Neurology
🇺🇸Dallas, Texas, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
CHRU de Lille - Hôpital Roger Salengro
🇫🇷Lille, France
Hospital Universitario de Bellvitge
🇪🇸Barcelona, Spain
London Health Sciences Centre
🇨🇦London, Canada
Kings College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Sunnybrook and Women's College and Health Sciences Centre
🇨🇦Toronto, Canada
Karolinska Universitetssjukhuset, Solna
🇸🇪Stockholm, Sweden
UZ Leuven
🇧🇪Leuven, Belgium
Prince of Wales Hospital
🇦🇺Randwick, New South Wales, Australia
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Methodist Neurological Institute
🇺🇸Houston, Texas, United States
University of Texas Health Sciences Center
🇺🇸San Antonio, Texas, United States
University of Nevada School of Medicine
🇺🇸Las Vegas, Nevada, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of California, Davis
🇺🇸Sacramento, California, United States
University of Washington
🇺🇸Seattle, Washington, United States
Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
University of California, Irvine
🇺🇸Orange, California, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Beaumont Hospital
🇮🇪Dublin, Ireland
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Providence ALS Center
🇺🇸Portland, Oregon, United States
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
University of South Florida Medical Center
🇺🇸Tampa, Florida, United States
Hospital for Special Care
🇺🇸New Britain, Connecticut, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Columbia University
🇺🇸New York, New York, United States
Drexel University College of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Mcgill University
🇨🇦Montreal, Quebec, Canada
Universitätsklinikum Jena
🇩🇪Jena, Germany
Bergmannsheil Gmbh
🇩🇪Bochum, Germany
Newcastle University Hospital - Clinical Ageing Research Unit
🇬🇧Newcastle, United Kingdom
Hospital La Paz
🇪🇸Madrid, Spain
Sahlgrenska Universitetssjukhuset
🇸🇪Göteborg, Sweden
Hospital Carlos III
🇪🇸Madrid, Spain
Walton Centre for Neurology & Neurosurgery
🇬🇧Liverpool, United Kingdom
Sheffield Institute for Transnational Neuroscience
🇬🇧Sheffield, United Kingdom
University of California at San Francisco - Fresno
🇺🇸Fresno, California, United States
Barrow Neurological Institute - St. Joseph's Hospital
🇺🇸Phoenix, Arizona, United States
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
St. Mary's Health Care
🇺🇸Grand Rapids, Michigan, United States
Wake Forest University
🇺🇸Winston-Salem, North Carolina, United States
CHU de Nice - Hôpital de l'Archet 1
🇫🇷Nice, France
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States