Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS)
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Registration Number
- NCT00647296
- Lead Sponsor
- Knopp Biosciences
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 194
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Placebo or Dexpramipexole Dexpramipexole 300 mg/day 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. Part 2: Dexpramipexole Dexpramipexole 300 mg/day 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. Part 1: Placebo or Dexpramipexole Placebo 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. Part 1: Placebo or Dexpramipexole Dexpramipexole 50 mg/day 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. Part 2: Dexpramipexole Dexpramipexole 50 mg/day 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. Part 1: Placebo or Dexpramipexole Dexpramipexole 150 mg/day 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. Part 2: Placebo washout Placebo At the beginning of Part 2, subjects received twice daily doses of placebo for approximately 4 weeks.
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group 12 weeks 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.
Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group 12 weeks 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.
Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group 12 weeks 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.
Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group 12 weeks 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.
- Secondary Outcome Measures
Name Time Method Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2 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.
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology 4 weeks 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.
Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings 4 weeks 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.
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group up to 76 weeks 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.
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group up to 76 weeks 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.
Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group 12 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 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.
Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group 12 weeks 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.
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements 4 weeks 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.
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results 4 weeks 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.
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group up to 76 weeks 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.
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 28 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 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.
Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score 4 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 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.Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4) 4 weeks 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.
Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group up to 76 weeks 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.
Trial Locations
- Locations (21)
Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
Drexel University College Of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
🇺🇸Los Angeles, California, United States
Bryan LGH Medical Center East
🇺🇸Lincoln, Nebraska, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Massachusettes General Hospital
🇺🇸Boston, Massachusetts, United States
Columbia University, Lou Gehrig MDA/ALS Research Center
🇺🇸New York, New York, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of Pittsburgh School of Medicine
🇺🇸Pittsburgh, Pennsylvania, United States
The Forbes Norris MDA/ALS Research Center
🇺🇸San Francisco, California, United States
University of Colorado Health Sciences Center
🇺🇸Aurora, Colorado, United States
Oregon Health Sciences University
🇺🇸Portland, Oregon, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
University of Texas Health Sciences Center of San Antonio
🇺🇸San Antonio, Texas, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States