Clinical trial NCT04046939: Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma
Official title: A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Biomarker Study of the Effects of Dexpramipexole on Eosinophils in Subjects With Eosinophilic Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Eosinophilic Asthma
Asthma
Keywords: Eosinophilic Asthma
Asthma
dexpramipexole
Lead sponsor: Knopp Biosciences
Sponsor class: INDUSTRY
First posted: 2019-08-06
Enrollment: 534
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Four-arm parallel assignment
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Change in Blood Absolute Eosinophil Count From Baseline to Week 12
timeFrame: Baseline, 12 Weeks
Secondary outcomes:
measure: Change in Pre-bronchodilator FEV1 (Liters) From Baseline to Week 12
timeFrame: Baseline, 12 Weeks
measure: Change in Asthma Control Questionnaire (ACQ-6) Score From Baseline to Week 12
timeFrame: Baseline, 12 Weeks
measure: Change in Post-bronchodilator FEV1 From Baseline to Week 12
timeFrame: Baseline, 12 Weeks
measure: Change in Quality of Life, as Measured by the Asthma Quality of Life Questionnaire (AQLQ) From Baseline to Week 12
timeFrame: Baseline, 12 Weeks
measure: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group Post Randomization Through Week 12
timeFrame: Immediately post-baseline up to Week 12
measure: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group Post Randomization Through Week 12
timeFrame: Immediately post-baseline up to Week 12
measure: Number of Participants With Potentially Clinically Significant Urinalysis Results by Treatment Group Post Randomization Through Week 12
timeFrame: Immediately post-baseline up to Week 12
measure: Number of Participants With Potentially Clinically Significant Vital Signs Results by Treatment Group Post Randomization Through Week 12
timeFrame: Immediately post-baseline up to Week 12
measure: Number of Participants With Potentially Clinically Significant ECG Results by Treatment Group Post Randomization Through Week 12
timeFrame: Immediately post-baseline up to Week 12
Other outcomes:
measure: Change in Nasal Eosinophil Peroxidase (Presented as Ratio to Protein) From Baseline to Week 12
timeFrame: Baseline, Week 12
measure: Change in Blood Absolute Blood Basophil Count From Baseline to Week 12
timeFrame: Baseline, Week 12
measure: Change in Fractional Exhaled Nitric Oxide (FeNO) From Baseline to Week 12
timeFrame: Baseline, Week 12
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Mission Viejo
country: United States
facility: Research Site
state: California
city: Westminster
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Daytona Beach
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Lawrenceville
country: United States
facility: Research Site
state: Georgia
city: Winder
country: United States
facility: Research Site
state: Georgia
city: Boise
country: United States
facility: Research Site
state: Idaho
city: Farmington Hills
country: United States
facility: Research Site
state: Michigan
city: Plymouth
country: United States
facility: Research site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: New Brunswick
country: United States
facility: Research Site
state: New Jersey
city: Corning
country: United States
facility: Research Site
state: New York
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Dublin
country: United States
facility: Research Site
state: Ohio
city: Edmond
country: United States
facility: Research Site
state: Oklahoma
city: Medford
country: United States
facility: Research Site
state: Oregon
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Anderson
country: United States
facility: Research Site
state: South Carolina
city: North Charleston
country: United States
facility: Research Site
state: South Carolina
city: Allen
country: United States
facility: Research Site
state: Texas
city: Boerne
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: El Paso
country: United States
facility: Research Site
state: Texas
Study officials:
References: