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Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma (AS201)

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: NCT04046939
Recruitment Status : Completed
First Posted : August 6, 2019
Results First Posted : December 22, 2021
Last Update Posted : March 28, 2022
Sponsor:
Information provided by (Responsible Party):
Knopp Biosciences

Brief Summary:
This is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, multi-center study to evaluate the clinical effects of oral administration of dexpramipexole for 12 weeks on peripheral blood eosinophil count in subjects with eosinophilic asthma.

Condition or disease Intervention/treatment Phase
Eosinophilic Asthma Asthma Drug: Dexpramipexole Drug: Placebo Phase 2

Detailed Description:
One hundred subjects will receive study drug or matching placebo over 12 weeks of consecutive dosing. Following a short Run-in Period, eligible subjects will enter the Primary Assessment Period and receive twice-daily dosing of study drug or placebo for 12 weeks. Following 12 weeks of treatment, subjects will enter a 12-week Eosinophil Recovery Period. The primary endpoint for the study is the change in blood absolute eosinophil count from Baseline to Week 12.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 534 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Four-arm parallel assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Biomarker Study of the Effects of Dexpramipexole on Eosinophils in Subjects With Eosinophilic Asthma
Actual Study Start Date : August 15, 2019
Actual Primary Completion Date : December 3, 2020
Actual Study Completion Date : March 2, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Placebo Comparator: placebo BID
Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks.
Drug: Placebo
placebo twice daily oral dosing for up to 12 weeks
Other Name: PBO

Active Comparator: 37.5 mg BID dexpramipexole
Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks.
Drug: Dexpramipexole
dexpramipexole twice daily oral dosing for up to 12 weeks
Other Names:
  • KNS-760704
  • BIIB050

Active Comparator: 75 mg BID dexpramipexole
Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks.
Drug: Dexpramipexole
dexpramipexole twice daily oral dosing for up to 12 weeks
Other Names:
  • KNS-760704
  • BIIB050

Active Comparator: 150 mg BID dexpramipexole
Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks.
Drug: Dexpramipexole
dexpramipexole twice daily oral dosing for up to 12 weeks
Other Names:
  • KNS-760704
  • BIIB050




Primary Outcome Measures :
  1. Change in Blood Absolute Eosinophil Count From Baseline to Week 12 [ Time Frame: Baseline, 12 Weeks ]
    The primary endpoint of this study was the change in AEC from Baseline to Week 12 on a ratio scale. The analysis used a mixed effects model repeated-measures (MMRM) with terms for log10 transformed baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and log10 transformed baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the log10 transformed post-baseline value minus the log10 transformed baseline value. The estimates of Geometric LS Means and their ratios were obtained by back transforming the corresponding estimates of LS means and their differences to the original scale.


Secondary Outcome Measures :
  1. Change in Pre-bronchodilator FEV1 (Liters) From Baseline to Week 12 [ Time Frame: Baseline, 12 Weeks ]
    FEV1 is defined as the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation.

  2. Change in Asthma Control Questionnaire (ACQ-6) Score From Baseline to Week 12 [ Time Frame: Baseline, 12 Weeks ]
    ACQ-6 is simple questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or as a result of treatment. The 6-point self-administered scale has items measuring asthma symptoms and rescue inhaler use. The ACQ score is the mean of the questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). The original protocol planned to analyze the ACQ-7 score. As a result of FEV1 testing restrictions imposed on the study during the COVID-19 pandemic, the analysis was prospectively modified to the ACQ-6 score prior to database lock. The ACQ-6 is a validated questionnaire and is identical to the ACQ-7, with the exception of FEV1 data that is also utilized in the ACQ-7 questionnaire total score calculation.

  3. Change in Post-bronchodilator FEV1 From Baseline to Week 12 [ Time Frame: Baseline, 12 Weeks ]
    Post-bronchodilator FEV1 is defined as the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation, after treatment with inhaled albuterol.

  4. Change in Quality of Life, as Measured by the Asthma Quality of Life Questionnaire (AQLQ) From Baseline to Week 12 [ Time Frame: Baseline, 12 Weeks ]
    The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma. The 32 questions in the AQLQ are divided into four domains; activity limitations, symptoms, emotional function, and environmental stimuli. Individual questions are equally weighted. The overall AQLQ score is the mean of the responses to each of the 32 questions and ranges from 1 to 7. A score 7.0 indicates that the patient has no impairments due to asthma and score 1.0 indicates severe impairment.

  5. Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group Post Randomization Through Week 12 [ Time Frame: Immediately post-baseline up to Week 12 ]
    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.

  6. Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group Post Randomization Through Week 12 [ Time Frame: Immediately post-baseline up to Week 12 ]
    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.

  7. Number of Participants With Potentially Clinically Significant Urinalysis Results by Treatment Group Post Randomization Through Week 12 [ Time Frame: Immediately post-baseline up to Week 12 ]
    Number of Participants with Potentially Clinically Significant Urinalysis Results (glycosuria, ketonuria, or proteinuria) by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline urinalysis value in each treatment group. Patients are only counted once per criterion per laboratory test. The number of participants with potential clinical important urinalysis findings at any post-baseline visit were reported.

  8. Number of Participants With Potentially Clinically Significant Vital Signs Results by Treatment Group Post Randomization Through Week 12 [ Time Frame: Immediately post-baseline up to Week 12 ]
    Number of Participants with Potentially Clinically Significant Vital Signs 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.

  9. Number of Participants With Potentially Clinically Significant ECG Results by Treatment Group Post Randomization Through Week 12 [ Time Frame: Immediately post-baseline up to Week 12 ]
    Number of Participants with Potentially Clinically Significant ECG 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.


Other Outcome Measures:
  1. Change in Nasal Eosinophil Peroxidase (Presented as Ratio to Protein) From Baseline to Week 12 [ Time Frame: Baseline, Week 12 ]
    The EPX:protein ratio was used to normalize the EPX for the quantity of sample, yielding the values in ng EPX per mg protein. The ratio of nasal Eosinophil Peroxidase to Protein is a biomarker for airway eosinophils. A lower ratio to Baseline represents a lowering in airway eosinophilia, which is a marker of successful drug therapy.

  2. Change in Blood Absolute Blood Basophil Count From Baseline to Week 12 [ Time Frame: Baseline, Week 12 ]
    The analysis used a mixed effects model repeated-measures MMRM with terms for baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the post-baseline value minus the baseline value. Basophils were enumerated as part of the WBC automated differential performed by the Central Laboratory.

  3. Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 12 [ Time Frame: Baseline, Week 12 ]
    FeNO is non-invasive biomarker of airway inflammation in asthma participants.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female ≥18 and <75 years of age at the time of consent
  • Physician diagnosis of asthma for ≥12 months (relative to Baseline) based on Global Initiative for Asthma (GINA) 2018 Guidelines
  • Asthma requiring treatment with, at a minimum, low dose inhaled corticosteroids in combination with a long-acting β2 agonist, on a stable dose for at least 1 month before Screening
  • Bronchodilator reversibility, as evidenced by ≥12% and ≥200 mL improvement in FEV1 15 to 25 minutes following inhalation of albuterol at Screening
  • Pre-bronchodilator FEV1 ≥40% and <80% of predicted at Screening and Baseline
  • AEC ≥0.30 x10^9/L at the Screening visit
  • ACQ-7 ≥1.5 at Screening
  • Negative pregnancy test at Baseline
  • Adherence ≥85% with twice-daily placebo taken during the Run-in Period

Exclusion Criteria:

  • Treatment for an asthma exacerbation within 8 weeks prior to Baseline visit
  • Treatment with systemic corticosteroids in the 8 weeks prior to Screening
  • Treatment with monoclonal antibody therapy, within 5-half-lives prior to Baseline
  • Treatment with selected drugs known to have a substantial risk of neutropenia
  • Absolute neutrophil count <2.0x10^9/L at Screening, or any documented history of absolute neutrophil count <2.0x10^9/L.
  • Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m^2 at Screening
  • Clinically significant abnormal laboratory or ECG values
  • Other medically significant illness
  • Use of any smoke or inhaled nicotine delivery device within 1 year prior to Screening
  • Pregnant women or women breastfeeding
  • Currently taking pramipexole or other dopamine agonists

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): NCT04046939


Locations
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United States, California
Research Site
Los Angeles, California, United States, 90048
Research Site
Mission Viejo, California, United States, 92691
Research Site
Westminster, California, United States, 92683
United States, Colorado
Research Site
Denver, Colorado, United States, 80230
United States, Florida
Research Site
Daytona Beach, Florida, United States, 32117
Research Site
Miami, Florida, United States, 33186
Research Site
Orlando, Florida, United States, 32803
Research Site
Tampa, Florida, United States, 33612
Research Site
Tampa, Florida, United States, 33634
United States, Georgia
Research Site
Lawrenceville, Georgia, United States, 30046
Research Site
Winder, Georgia, United States, 30680
United States, Idaho
Research Site
Boise, Idaho, United States, 83706
United States, Michigan
Research Site
Farmington Hills, Michigan, United States, 48336
United States, Minnesota
Research site
Plymouth, Minnesota, United States, 55441
United States, Missouri
Research Site
Saint Louis, Missouri, United States, 63110
Research Site
Saint Louis, Missouri, United States, 63141
United States, Nevada
Research Site
Las Vegas, Nevada, United States, 89119
United States, New Jersey
Research Site
New Brunswick, New Jersey, United States, 08901
United States, New York
Research Site
Corning, New York, United States, 14830
Research Site
New Hyde Park, New York, United States, 11042
United States, North Carolina
Research Site
Raleigh, North Carolina, United States, 27607
Research Site
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Research Site
Cincinnati, Ohio, United States, 45231
Research Site
Cincinnati, Ohio, United States, 45242
Research Site
Columbus, Ohio, United States, 43235
Research Site
Dublin, Ohio, United States, 43016
United States, Oklahoma
Research Site
Edmond, Oklahoma, United States, 73034
United States, Oregon
Research Site
Medford, Oregon, United States, 97504
Research Site
Portland, Oregon, United States, 97202
United States, Pennsylvania
Research Site
Pittsburgh, Pennsylvania, United States, 15205
United States, South Carolina
Research Site
Anderson, South Carolina, United States, 29621
Research Site
North Charleston, South Carolina, United States, 29406
United States, Texas
Research Site
Allen, Texas, United States, 75013
Research Site
Boerne, Texas, United States, 78006
Research Site
Dallas, Texas, United States, 75240
Research Site
El Paso, Texas, United States, 79902
Sponsors and Collaborators
Knopp Biosciences
  Study Documents (Full-Text)

Documents provided by Knopp Biosciences:
Study Protocol  [PDF] July 16, 2019
Statistical Analysis Plan  [PDF] December 22, 2020

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Responsible Party: Knopp Biosciences
ClinicalTrials.gov Identifier: NCT04046939    
Other Study ID Numbers: KNS-760704-AS201
First Posted: August 6, 2019    Key Record Dates
Results First Posted: December 22, 2021
Last Update Posted: March 28, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Knopp Biosciences:
Eosinophilic Asthma
Asthma
dexpramipexole
Additional relevant MeSH terms:
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Pramipexole
Asthma
Pulmonary Eosinophilia
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Hypereosinophilic Syndrome
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents