Phase 3 Extension Study of Dexpramipexole in ALS

Amyotrophic Lateral Sclerosis Clinical Trial

— ENVISION  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01622088
• Other study ID #: 223AS304
• Secondary ID: EUDRA CT #: 2011
• Status: Terminated
• Phase: Phase 3
• Start date: June 2012
• Est. completion date: February 2013

Study information

• Verified date: April 2022
• Source: Knopp Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Terminated
• Enrollment: 616
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Dexpramipexole
Oral tablet 150 mg given twice daily (BID)

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	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 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 (2)

Lead Sponsor	Collaborator
Knopp Biosciences	Biogen

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	Number of Subjects Who Reported an Adverse Event	The number of subjects who reported an adverse event during the study	Baseline through end of study (maximum 226 days: approximately 32.2 weeks)
Primary	Number of Subjects Who Experienced a Serious Adverse Event	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)
Primary	Number of Subjects Who Discontinued the Study Treatment Due to an Adverse Event	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)
Primary	Number of Participants With Potentially Clinically Significant Vital Sign Results	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)
Primary	Number of Participants With Potentially Clinically Significant Hematology Results	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)
Primary	Number of Participants With Potentially Clinically Significant Blood Chemistry Results	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)
Primary	Number of Participants With Potentially Clinically Significant ECG Results	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	Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to End of Study	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
Secondary	Slope of Sniff Nasal Inspiratory Pressure (SNIP) From Baseline to End of Study	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
Secondary	Death up to 6 Months	Kaplan-Meier estimate of percentage of subjects who died up to 6 months	6 Months
Secondary	Percentage of Participants With Death or Death Equivalent up to 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