Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Eosinophilic Asthma, Asthma

Intervention / Treatment
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* Drug: Dexpramipexole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Four-arm parallel assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo BID<br>Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks. | Drug: Placebo<br>* placebo twice daily oral dosing for up to 12 weeks<br>* Other names: PBO;|
| Active Comparator: 37.5 mg BID dexpramipexole<br>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<br>* dexpramipexole twice daily oral dosing for up to 12 weeks<br>* Other names: BIIB050;|
| Active Comparator: 75 mg BID dexpramipexole<br>Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks. | Drug: Dexpramipexole<br>* dexpramipexole twice daily oral dosing for up to 12 weeks<br>* Other names: BIIB050;|
| Active Comparator: 150 mg BID dexpramipexole<br>Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks. | Drug: Dexpramipexole<br>* dexpramipexole twice daily oral dosing for up to 12 weeks<br>* Other names: BIIB050;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Blood Absolute Eosinophil Count From Baseline to Week 12 | 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. | Baseline, 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pre-bronchodilator FEV1 (Liters) From Baseline to Week 12 | FEV1 is defined as the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation. | Baseline, 12 Weeks | 
| Change in Asthma Control Questionnaire (ACQ-6) Score From Baseline to Week 12 | 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. | Baseline, 12 Weeks | 
| Change in Post-bronchodilator FEV1 From Baseline to Week 12 | 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. | Baseline, 12 Weeks | 
| Change in Quality of Life, as Measured by the Asthma Quality of Life Questionnaire (AQLQ) From Baseline to Week 12 | 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. | Baseline, 12 Weeks | 
| Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group Post Randomization Through 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. | Immediately post-baseline up to Week 12 | 
| Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group Post Randomization Through 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. | Immediately post-baseline up to Week 12 | 
| Number of Participants With Potentially Clinically Significant Urinalysis Results by Treatment Group Post Randomization Through 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. | Immediately post-baseline up to Week 12 | 
| Number of Participants With Potentially Clinically Significant Vital Signs Results by Treatment Group Post Randomization Through 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. | Immediately post-baseline up to Week 12 | 
| Number of Participants With Potentially Clinically Significant ECG Results by Treatment Group Post Randomization Through 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. | Immediately post-baseline up to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eosinophilic Asthma, Asthma, dexpramipexole