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Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS) (CL201)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00647296
Recruitment Status : Completed
First Posted : March 31, 2008
Results First Posted : July 8, 2021
Last Update Posted : July 8, 2021
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Placebo Drug: Dexpramipexole 50 mg/day Drug: Dexpramipexole 150 mg/day Drug: Dexpramipexole 300 mg/day Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 194 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Matching placebo during Part 1 and Part 2 placebo washout.
Primary Purpose: Treatment
Official Title: A 2-Part, Randomized, Double-Blind, Safety and Tolerability Study Evaluating KNS-760704 in Patients With Amyotrophic Lateral Sclerosis (ALS)
Actual Study Start Date : April 9, 2008
Actual Primary Completion Date : July 31, 2009
Actual Study Completion Date : September 4, 2009


Arm Intervention/treatment
Placebo Comparator: 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.
Drug: Placebo
Placebo: 2 tablets taken orally twice daily

Drug: Dexpramipexole 50 mg/day
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Other Names:
  • KNS-760704
  • BIIB050

Drug: Dexpramipexole 150 mg/day
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
Other Names:
  • KNS-760704
  • BIIB050

Drug: Dexpramipexole 300 mg/day
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Other Names:
  • KNS-760704
  • BIIB050

Experimental: Part 2: Placebo washout
At the beginning of Part 2, subjects received twice daily doses of placebo for approximately 4 weeks.
Drug: Placebo
Placebo: 2 tablets taken orally twice daily

Experimental: 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.
Drug: Dexpramipexole 50 mg/day
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
Other Names:
  • KNS-760704
  • BIIB050

Drug: Dexpramipexole 300 mg/day
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Other Names:
  • KNS-760704
  • BIIB050




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group [ Time Frame: 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.

  2. Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group [ Time Frame: 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.

  3. Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology [ Time Frame: 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.

  4. Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results [ Time Frame: 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.

  5. Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings [ Time Frame: 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.

  6. Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements [ Time Frame: 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.

  7. Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score [ Time Frame: 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.


  8. Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4) [ Time Frame: 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.

  9. Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group [ Time Frame: 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.

  10. Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group [ Time Frame: 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.

  11. Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group [ Time Frame: 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.

  12. Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group [ Time Frame: 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.

  13. 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 [ Time Frame: 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.

  14. Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group [ Time Frame: 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.



Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   21 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00647296


Locations
Show Show 21 study locations
Sponsors and Collaborators
Knopp Biosciences
Publications of Results:
Layout table for additonal information
Responsible Party: Knopp Biosciences
ClinicalTrials.gov Identifier: NCT00647296    
Other Study ID Numbers: KNS-760704-CL201
First Posted: March 31, 2008    Key Record Dates
Results First Posted: July 8, 2021
Last Update Posted: July 8, 2021
Last Verified: March 2021
Keywords provided by Knopp Biosciences:
ALS
Amyotrophic Lateral Sclerosis
Lou Gehrig
Lou Gehrig's
Lou Gehrig's disease
Motor Neuron Disease
Nervous System Diseases
KNS-760704
BIIB050
Additional relevant MeSH terms:
Layout table for MeSH terms
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Pramipexole
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents