Clinical trial NCT00647296: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Knopp Biosciences
Sponsor class: INDUSTRY
First posted: 2008-03-31
Enrollment: 194
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
timeFrame: 12 weeks
measure: Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
timeFrame: 12 weeks
measure: Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
timeFrame: 12 weeks
measure: Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
timeFrame: 12 weeks
Secondary outcomes:
measure: Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group
timeFrame: 12 weeks
measure: Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group
timeFrame: 12 weeks
measure: Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology
timeFrame: 4 weeks
measure: Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results
timeFrame: 4 weeks
measure: Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: 4 weeks
measure: Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements
timeFrame: 4 weeks
measure: Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score
timeFrame: 4 weeks
measure: Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4)
timeFrame: 4 weeks
measure: Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
timeFrame: up to 76 weeks
measure: Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
timeFrame: up to 76 weeks
measure: Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
timeFrame: up to 76 weeks
measure: Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
timeFrame: up to 76 weeks
measure: 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
timeFrame: 28 weeks
measure: Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group
timeFrame: Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
state: California
city: San Francisco
country: United States
facility: The Forbes Norris MDA/ALS Research Center
state: California
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusettes General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lincoln
country: United States
facility: Bryan LGH Medical Center East
state: Nebraska
city: New York
country: United States
facility: Columbia University, Lou Gehrig MDA/ALS Research Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College Of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh School of Medicine
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: San Antonio
country: United States
facility: University of Texas Health Sciences Center of San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References:
citation: 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.