A 2-Part, Randomized, Double-Blind, Safety and Tolerability Study Evaluating KNS-760704 in Patients With Amyotrophic Lateral Sclerosis (ALS)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 194
- Locations
- 21
- Primary Endpoint
- Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Matching placebo during Part 1 and Part 2 placebo washout.
Eligibility Criteria
- Ages
- 21 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Part 1: Placebo or Dexpramipexole
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.
Intervention: Placebo (Drug)
Part 1: Placebo or Dexpramipexole
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.
Intervention: Dexpramipexole 50 mg/day (Drug)
Part 1: Placebo or Dexpramipexole
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.
Intervention: Dexpramipexole 150 mg/day (Drug)
Part 1: Placebo or Dexpramipexole
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.
Intervention: Dexpramipexole 300 mg/day (Drug)
Part 2: Placebo washout
At the beginning of Part 2, subjects received twice daily doses of placebo for approximately 4 weeks.
Intervention: Placebo (Drug)
Part 2: Dexpramipexole
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.
Intervention: Dexpramipexole 50 mg/day (Drug)
Part 2: Dexpramipexole
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.
Intervention: Dexpramipexole 300 mg/day (Drug)
Outcomes
Primary Outcomes
Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
- 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)
- Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology(4 weeks)
- Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings(4 weeks)
- Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group(up to 76 weeks)
- Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group(up to 76 weeks)
- Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group(12 weeks)
- Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group(12 weeks)
- Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements(4 weeks)
- Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results(4 weeks)
- Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group(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(28 weeks)
- Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score(4 weeks)
- Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4)(4 weeks)
- Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group(up to 76 weeks)