Safety and Tolerability Study of KNS-760704 in Amyotrophi... | NCT00647296 | Trialant
NCT00647296
Sponsor
Knopp Biosciences
Status
Completed
Last Update Posted
Jul 8, 2021Actual
Enrollment
194Actual
Phase
Phase 2
Conditions
Amyotrophic Lateral Sclerosis
Interventions
Placebo
Dexpramipexole 50 mg/day
Dexpramipexole 150 mg/day
Dexpramipexole 300 mg/day
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT00647296
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
KNS-760704-CL201
Secondary IDs
Not provided
Brief Title
Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS)
Official Title
A 2-Part, Randomized, Double-Blind, Safety and Tolerability Study Evaluating KNS-760704 in Patients With Amyotrophic Lateral Sclerosis (ALS)
Acronym
CL201
Organization
Knopp BiosciencesINDUSTRY
Status Module
Record Verification Date
Mar 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Apr 9, 2008Actual
Primary Completion Date
Jul 31, 2009Actual
Completion Date
Sep 4, 2009Actual
First Submitted Date
Mar 26, 2008
First Submission Date that Met QC Criteria
Mar 28, 2008
First Posted Date
Mar 31, 2008Estimated
Results Waived
Not provided
Results First Submitted Date
Mar 4, 2021
Results First Submitted that Met QC Criteria
Jun 16, 2021
Results First Posted Date
Jul 8, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jan 25, 2011
Certification/Extension First Submitted that Passed QC Review
Feb 1, 2011
Certification/Extension First Posted Date
Feb 8, 2011Estimated
Last Update Submitted Date
Jun 16, 2021
Last Update Posted Date
Jul 8, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Knopp BiosciencesINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This was a 2-part study of dexpramipexole in patients with ALS.
Part 1 was a randomized, placebo-controlled, multi-center study to evaluate the safety, tolerability, and clinical effects of oral administration of 3 dosage levels of dexpramipexole vs. placebo for 12 weeks.
Part 2 was a randomized, double-blind, 2-arm, parallel group, extension study evaluating the safety, tolerability, and clinical effects of oral administration of 2 dosage levels of dexpramipexole for up to 72 weeks.
Detailed Description
This study was a two-part, multicenter, double-blind study in subjects with ALS to evaluate the safety and tolerability of dexpramipexole treatment, as well as the preliminary effects on measures of clinical function and mortality of dexpramipexole treatment.
In part 1, 102 subjects with ALS were randomized at 20 US sites to receive placebo, dexpramipexole at 50 mg/day; dexpramipexole at 150 mg/day; or dexpramipexole at 300 mg/day for 12 weeks. Participants who completed Part 1 were eligible to enroll into Part 2.
Part 2 was a randomized, double-blind, 2-arm, parallel-group, extension study evaluating the longer-term safety, tolerability, and clinical effects of oral administration of 2 dosage levels of dexpramipexole. In part 2, following a 4-week, placebo washout, continuing subjects received dexpramipexole at 50 mg/day or 300 mg/day as double-blind treatment for up to 72 additional weeks (Part 2 duration was up to a total of 76 weeks, including the 4 week placebo portion).
Conditions Module
Conditions
Amyotrophic Lateral Sclerosis
Keywords
ALS
Amyotrophic Lateral Sclerosis
Lou Gehrig
Lou Gehrig's
Lou Gehrig's disease
Motor Neuron Disease
Nervous System Diseases
KNS-760704
BIIB050
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
194Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part 1: Placebo or Dexpramipexole
Placebo Comparator
During Part 1, subjects received twice daily doses of dexpramipexole (50 mg/day, 150 mg/day, or 300 mg/day) or matching placebo for approximately 12 weeks.
Drug: Placebo
Drug: Dexpramipexole 50 mg/day
Drug: Dexpramipexole 150 mg/day
Drug: Dexpramipexole 300 mg/day
Part 2: Placebo washout
Experimental
At the beginning of Part 2, subjects received twice daily doses of placebo for approximately 4 weeks.
Drug: Placebo
Part 2: Dexpramipexole
Experimental
Following the Part 2 placebo washout, subjects received dexpramipexole (50 mg/day or 300 mg/day), subjects received twice daily doses of placebo for up to 18 months.
Drug: Dexpramipexole 50 mg/day
Drug: Dexpramipexole 300 mg/day
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Placebo
Drug
Placebo: 2 tablets taken orally twice daily
Part 1: Placebo or Dexpramipexole
Part 2: Placebo washout
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. 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.
12 weeks
Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. 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.
12 weeks
Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
12 weeks
Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
12 weeks
Secondary Outcomes
Measure
Description
Time Frame
Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group
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. 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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria
Patients with ALS symptom onset < 24 months from randomization
Patients with upright vital capacity (VC) > 65% of predicted for age, height, and gender
Exclusion Criteria:
Patients in whom causes of neuromuscular weakness other than ALS have not been excluded
Patients without clinical evidence of upper motor neuron dysfunction
Patients with clinically suspected ALS according to the World Federation of Neurology El Escorial criteria
Patients with prior exposure to KNS-760704 or the R(+) enantiomer of pramipexole (i.e., R(+)-pramipexole)
Patients taking other investigational agents (including lithium) within 30 days of randomization or during the study
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
21 Years
Maximum Age
80 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Not provided
Locations
Facility
Status
City
State
ZIP
Country
Contacts
University of Arkansas for Medical Sciences
Little Rock
Arkansas
72205
United States
UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
Cudkowicz M, Bozik ME, Ingersoll EW, Miller R, Mitsumoto H, Shefner J, Moore DH, Schoenfeld D, Mather JL, Archibald D, Sullivan M, Amburgey C, Moritz J, Gribkoff VK. The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis. Nat Med. 2011 Nov 20;17(12):1652-6. doi: 10.1038/nm.2579.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
Study conducted in 2 parts: When the first 12 weeks (Part 1) was completed, eligible continuing subjects entered a 4 week placebo washout before being re-randomized to receive either 50 mg/day dexpramipexole or 300 mg/day dexpramipexole for up to 72 additional weeks.
Recruitment Details
Subjects were recruited for the study across 20 recruiting centers US between 09 April 2008 and 26 January 2009 in medical centers located the USA.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo Twice Daily
Placebo (PBO) BID (twice daily)
FG001
50 mg/Day Dexpramipexole
dexpramipexole 25 mg BID (twice daily)
Periods
Title
Milestones
Reasons Not Completed
Part 1: 12-week Double-Blind Treatment
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Quadruple
Masking Description
Matching placebo during Part 1 and Part 2 placebo washout.
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Part 1: Placebo or Dexpramipexole
Part 2: Dexpramipexole
KNS-760704
BIIB050
Dexpramipexole 150 mg/day
Drug
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
Part 1: Placebo or Dexpramipexole
KNS-760704
BIIB050
Dexpramipexole 300 mg/day
Drug
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Part 1: Placebo or Dexpramipexole
Part 2: Dexpramipexole
KNS-760704
BIIB050
12 weeks
Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group
Slope of change in Upright Vital Capacity (percent predicted upright vital capacity) from Baseline to Week 12. A negative change/slope indicates clinical worsening. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis as percent predicted upright vital capacity. Units for slope are change per month in percent predicted upright vital capacity.
12 weeks
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. 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.
4 weeks
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. 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.
4 weeks
Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings
Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
4 weeks
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements
Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
4 weeks
Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score
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.
Units are points on the ALSFRS-R score as an absolute change from the baseline of the placebo washout to week 4 of the placebo washout.
4 weeks
Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4)
Absolute change in Upright Vital Capacity From Baseline to Week 4. Units are percent of predicted Upright Vital Capacity. A negative change indicates clinical worsening.
4 weeks
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. 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 parameter.
up to 76 weeks
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. 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 parameter.
up to 76 weeks
Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. 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 parameter.
up to 76 weeks
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. 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 parameter.
up to 76 weeks
Part 2 Double-Blind Treatment: Slope of the ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 28 by Treatment Group
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. 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 n units on the ALSFRS-R scale.
28 weeks
Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group
Slope of Upright Vital Capacity (percent predicted) through Week 28. A negative change indicates clinical worsening. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis percent predicted upright vital capacity. Units for slope are change per month in percent predicted upright vital capacity.
Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2
Los Angeles
California
90095
United States
The Forbes Norris MDA/ALS Research Center
San Francisco
California
94115
United States
University of Colorado Health Sciences Center
Aurora
Colorado
80045
United States
University of Miami Miller School of Medicine
Miami
Florida
33136
United States
University of Kansas Medical Center
Kansas City
Kansas
66160
United States
Johns Hopkins University School of Medicine
Baltimore
Maryland
21228
United States
Massachusettes General Hospital
Boston
Massachusetts
02129
United States
Washington University School of Medicine
St Louis
Missouri
63110
United States
Bryan LGH Medical Center East
Lincoln
Nebraska
68506
United States
Columbia University, Lou Gehrig MDA/ALS Research Center
New York
New York
10032
United States
SUNY Upstate Medical University
Syracuse
New York
13210
United States
Oregon Health Sciences University
Portland
Oregon
97239
United States
Penn State Hershey Medical Center
Hershey
Pennsylvania
17033
United States
Drexel University College Of Medicine
Philadelphia
Pennsylvania
19102
United States
University of Pittsburgh School of Medicine
Pittsburgh
Pennsylvania
15213
United States
Vanderbilt University Medical Center
Nashville
Tennessee
37232
United States
University of Texas Health Sciences Center of San Antonio
San Antonio
Texas
78229
United States
University of Utah
Salt Lake City
Utah
84132
United States
University of Virginia Health System
Charlottesville
Virginia
22908
United States
University of Washington
Seattle
Washington
98195
United States
FG002
150 mg/Day Dexpramipexole
dexpramipexole 75 mg BID (twice daily)
FG003
300 mg/Day Dexpramipexole
dexpramipexole 150 mg BID (twice daily)
FG00027 subjects
FG00123 subjects
FG00226 subjects
FG00326 subjects
COMPLETED
FG00026 subjects
FG00122 subjects
FG00226 subjects
FG00324 subjects
NOT COMPLETED
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0032 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
Adverse Event
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
Physician Decision
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
Part 2: 4-week Placebo Washout
Type
Comment
Milestone Data
STARTED
FG00097 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
COMPLETED
FG00092 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
NOT COMPLETED
FG0005 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG003
Part 2: 76-week Double-Blind Treatment
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG00148 subjects
FG0020 subjects
FG00344 subjects
COMPLETED
FG0000 subjects
FG00133 subjects
FG0020 subjects
FG00330 subjects
NOT COMPLETED
FG0000 subjects
FG00115 subjects
FG0020 subjects
FG00314 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0015 subjects
FG0020 subjects
FG003
all patients who signed an informed consent and were screened for the study, whether randomized or not
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo
PBO BID for 12 weeks
BG001
50 mg/Day
25 mg BID for 12 weeks
BG002
150 mg/Day
75 mg BID for 12 weeks
BG003
300 mg/Day
150 mg BID for 12 weeks
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00027
BG00123
BG00226
BG00326
BG004102
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00055.8± 9.07
BG00158.1± 10.20
BG00256.01± 11.03
BG003
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
< 50 years
Title
Measurements
BG0007
BG0016
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00014
BG00114
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Height
Mean
Standard Deviation
cm
Title
Denominators
Categories
Title
Measurements
BG000170.28± 10.349
BG001170.34± 8.209
BG002
Weight
Mean
Standard Deviation
kg
Title
Denominators
Categories
Title
Measurements
BG00074.7± 15.83
BG00178.2± 19.89
BG002
Body mass index
Mean
Standard Deviation
kg/m^2
Title
Denominators
Categories
Title
Measurements
BG00025.66± 3.934
BG00126.86± 6.369
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. 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.
Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
12 weeks
ID
Title
Description
OG000
Placebo
PBO BID for 12 weeks
OG001
50 mg/Day
25 mg dexpramipexole BID for 12 weeks
OG002
150 mg/Day
75 mg dexpramipexole BID for 12 weeks
OG003
300 mg/Day
150 mg dexpramipexole BID for 12 weeks
Units
Counts
Participants
OG00027
OG00123
OG00226
OG003
Title
Denominators
Categories
White Blood Cell Count (x10^3/uL) < 2000/uL
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. 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.
Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
12 weeks
ID
Title
Description
OG000
Placebo
PBO BID for 12 weeks
OG001
50 mg/Day
25 mg dexpramipexole BID for 12 weeks
OG002
150 mg/Day
75 mg dexpramipexole BID for 12 weeks
OG003
300 mg/Day
150 mg dexpramipexole BID for 12 weeks
Primary
Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
12 weeks
ID
Title
Description
OG000
Placebo
PBO BID for 12 weeks
OG001
50 mg/Day
25 mg dexpramipexole BID for 12 weeks
OG002
150 mg/Day
75 mg dexpramipexole BID for 12 weeks
OG003
300 mg/Day
150 mg dexpramipexole BID for 12 weeks
Primary
Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
12 weeks
ID
Title
Description
OG000
Placebo
PBO BID for 12 weeks
OG001
50 mg/Day
25 mg dexpramipexole BID for 12 weeks
OG002
150 mg/Day
75 mg dexpramipexole BID for 12 weeks
OG003
300 mg/Day
150 mg dexpramipexole BID for 12 weeks
Secondary
Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group
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. 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.
Randomized subjects who had at least 1 post-baseline clinical status evaluation within 7 days of discontinuing study drug
Posted
Least Squares Mean
95% Confidence Interval
slope
12 weeks
ID
Title
Description
OG000
Placebo
Two matching PBO tablets taken orally twice daily for 12 weeks
OG001
Dexpramipexole (50 mg/Day)
Two 12.5 mg tablets taken orally twice daily for 12 weeks
OG002
Dexpramipexole (150 mg/Day)
Two 37.5 mg tablets taken orally twice daily for 12 weeks
Secondary
Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group
Slope of change in Upright Vital Capacity (percent predicted upright vital capacity) from Baseline to Week 12. A negative change/slope indicates clinical worsening. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis as percent predicted upright vital capacity. Units for slope are change per month in percent predicted upright vital capacity.
Randomized subjects who had at least 1 post-baseline clinical status evaluation with 7 days of discontinuing study drug
Posted
Least Squares Mean
95% Confidence Interval
slope
12 weeks
ID
Title
Description
OG000
Placebo
Two matching PBO tablets taken orally twice daily for 12 weeks
OG001
Dexpramipexole (50 mg/Day)
Two 12.5 mg tablets taken orally twice daily for 12 weeks
OG002
Dexpramipexole (150 mg/Day)
Two 37.5 mg tablets taken orally twice daily for 12 weeks
OG003
Dexpramipexole (300 mg/Day)
Secondary
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. 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.
Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug during the placebo washout.
Posted
Count of Participants
Participants
4 weeks
ID
Title
Description
OG000
Placebo
Part 2: 4-week placebo washout
Units
Counts
Participants
OG000
Secondary
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. 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.
Safety Population: Data from all enrolled subjects who were randomized in Part 2, received at least 1 dose of study drug, and had one post BL evaluation during the placebo washout.
Posted
Count of Participants
Participants
4 weeks
ID
Title
Description
OG000
Placebo
Part 2: 4-week placebo washout
Units
Counts
Participants
OG000
Secondary
Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings
Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
Safety Population: Data from all enrolled subjects who were randomized in Part 1, received at least 1 dose of study drug, and have at least on evaluation post baseline.
Posted
Count of Participants
Participants
4 weeks
ID
Title
Description
OG000
Placebo
Part 2: 4-week placebo washout
Units
Counts
Participants
OG000
Secondary
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements
Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
4 weeks
ID
Title
Description
OG000
Placebo
Part 2: 4-week placebo washout
Units
Counts
Participants
OG000
Secondary
Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score
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.
Units are points on the ALSFRS-R score as an absolute change from the baseline of the placebo washout to week 4 of the placebo washout.
Randomized subjects who had at least 1 post-baseline clinical status evaluation with 7 days of discontinuing study drug
Posted
Mean
Standard Error
units on a scale
4 weeks
ID
Title
Description
OG000
Placebo
Part 2: 4-week placebo washout
Units
Counts
Participants
OG000
Secondary
Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4)
Absolute change in Upright Vital Capacity From Baseline to Week 4. Units are percent of predicted Upright Vital Capacity. A negative change indicates clinical worsening.
Randomized subjects who had at least 1 post-baseline clinical status evaluation with 7 days of discontinuing study drug
Posted
Mean
Standard Error
units on a scale
4 weeks
ID
Title
Description
OG000
Placebo
Part 2: 4-week placebo washout
Units
Counts
Participants
OG000
Secondary
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. 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 parameter.
Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
up to 76 weeks
ID
Title
Description
OG000
50 mg/Day
25 mg BID for 12 weeks
OG001
300 mg/Day
150 mg BID for 12 weeks
Units
Counts
Participants
OG000
Secondary
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. 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 parameter.
Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
up to 76 weeks
ID
Title
Description
OG000
50 mg/Day
25 mg BID for 12 weeks
OG001
300 mg/Day
150 mg BID for 12 weeks
Units
Counts
Participants
OG000
Secondary
Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. 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 parameter.
Safety Population: Data from all enrolled subjects who were randomized in Part 2, received at least 1 dose of study drug, and had at least one evaluation post baseline.
Posted
Count of Participants
Participants
up to 76 weeks
ID
Title
Description
OG000
50 mg/Day
25 mg BID for 12 weeks
OG001
300 mg/Day
150 mg BID for 12 weeks
Units
Counts
Participants
OG000
Secondary
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. 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 parameter.
Safety Population: Data from all enrolled subjects who were randomized in Part 1, received at least 1 dose of study drug, and had at least one post baseline evaluation.
Posted
Count of Participants
Participants
up to 76 weeks
ID
Title
Description
OG000
50 mg/Day
25 mg BID for 12 weeks
OG001
300 mg/Day
150 mg BID for 12 weeks
Units
Counts
Participants
OG000
Secondary
Part 2 Double-Blind Treatment: Slope of the ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 28 by Treatment Group
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. 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 n units on the ALSFRS-R scale.
Randomized subjects who had at least 1 post-baseline clinical status evaluation with 7 days of discontinuing study drug
Posted
Least Squares Mean
95% Confidence Interval
slope
28 weeks
ID
Title
Description
OG000
Dexpramipexole (50 mg/Day)
Two 12.5 mg tablets taken orally twice daily for 12 weeks
OG001
Dexpramipexole (300 mg/Day)
Two 75 mg tablets taken orally twice daily for 12 weeks
Units
Counts
Participants
Secondary
Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group
Slope of Upright Vital Capacity (percent predicted) through Week 28. A negative change indicates clinical worsening. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis percent predicted upright vital capacity. Units for slope are change per month in percent predicted upright vital capacity.
Randomized subjects who had at least 1 post-baseline clinical status evaluation with 7 days of discontinuing study drug.
Posted
Least Squares Mean
95% Confidence Interval
slope
Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2
ID
Title
Description
OG000
Dexpramipexole (50 mg/Day)
Two 12.5 mg tablets taken orally twice daily for 12 weeks
OG001
Dexpramipexole (300 mg/Day)
Two 75 mg tablets taken orally twice daily for 12 weeks
Units
Counts
Participants
Time Frame
Part 1: up to 12 weeks; Part 2 Placebo washout: up to 4 weeks; Part 2 Treatment period: up to 18 months
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part 1: Placebo
Two matching PBO tablets taken orally twice daily for 12 weeks
0
27
0
27
25
27
EG001
Part 1: Dexpramipexole (50 mg/Day)
Two 12.5 mg tablets taken orally twice daily for 12 weeks
0
23
2
23
19
23
EG002
Part 1: Dexpramipexole (150 mg/Day)
Two 37.5 mg tablets taken orally twice daily for 12 weeks
0
26
0
26
25
26
EG003
Part 1: Dexpramipexole (300 mg/Day)
Two 75 mg tablets taken orally twice daily for 12 weeks
0
26
3
26
23
26
EG004
Part 2: Placebo Washout
Two matching PBO tablets taken orally twice daily for 4 weeks
3
97
5
97
46
97
EG005
Part 2: Dexpramipexole (50 mg/Day)
Two 12.5 mg tablets taken orally twice daily for up to 18 months
15
48
14
48
46
48
EG006
Part 2: Dexpramipexole (300 mg/Day)
Two 75 mg tablets taken orally twice daily for up to 18 months