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Completed

NCT Number: NCT04046939

Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma

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.

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Key information

Conditions

Eosinophilic Asthma Asthma Bronchial Diseases Eosinophilia Hematologic Diseases Hemic and Lymphatic Diseases Hypereosinophilic Syndrome Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Leukocyte Disorders Lung Diseases Lung Diseases, Obstructive Pulmonary Eosinophilia Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

18 year–74 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site, Los Angeles, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Dexpramipexole

Drug

dexpramipexole twice daily oral dosing for up to 12 weeks

Other names: KNS-760704, BIIB050

Placebo

Drug

placebo twice daily oral dosing for up to 12 weeks

Other names: PBO

Primary outcomes

  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 outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Knopp Biosciences

Industry

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Biomarker Study of the Effects of Dexpramipexole on Eosinophils in Subjects With Eosinophilic Asthma

Acronym: EXHALE-1

Important dates

Study start
2019
Primary completion
2020
Study completion
2021
First posted
Aug 6, 2019
Registry last updated
Apr 13, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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