Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis Clinical Trial

— CL201  

Official title:

A 2-Part, Randomized, Double-Blind, Safety and Tolerability Study Evaluating KNS-760704 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00647296
• Other study ID #: KNS-760704-CL201
• Status: Completed
• Phase: Phase 2
• Start date: April 9, 2008
• Est. completion date: September 4, 2009

Study information

• Verified date: March 2021
• Source: Knopp Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 194
• Est. completion date: September 4, 2009
• Est. primary completion date: July 31, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Placebo
Placebo: 2 tablets taken orally twice daily
• Dexpramipexole 50 mg/day
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
• Dexpramipexole 150 mg/day
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
• Dexpramipexole 300 mg/day
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily

Locations

Country	Name	City	State
United States	University of Colorado Health Sciences Center	Aurora	Colorado
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Massachusettes General Hospital	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Bryan LGH Medical Center East	Lincoln	Nebraska
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center	Los Angeles	California
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University, Lou Gehrig MDA/ALS Research Center	New York	New York
United States	Drexel University College Of Medicine	Philadelphia	Pennsylvania
United States	University of Pittsburgh School of Medicine	Pittsburgh	Pennsylvania
United States	Oregon Health Sciences University	Portland	Oregon
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 of San Antonio	San Antonio	Texas
United States	The Forbes Norris MDA/ALS Research Center	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Knopp Biosciences

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 sclero — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	12 weeks
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.	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.	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.	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.	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.	12 weeks
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.	4 weeks
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.	4 weeks
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.	4 weeks
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.	4 weeks
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.	4 weeks
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.	4 weeks
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.	up to 76 weeks
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.	up to 76 weeks
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.	up to 76 weeks
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.	up to 76 weeks
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.	28 weeks
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.	Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2