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Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma (EXHALE-1)

Primary Purpose

Eosinophilic Asthma, Asthma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Dexpramipexole

Placebo

About this trial

This is an interventional treatment trial for Eosinophilic Asthma focused on measuring Eosinophilic Asthma, Asthma, dexpramipexole

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Active Comparator

Arm Label

placebo BID

37.5 mg BID dexpramipexole

75 mg BID dexpramipexole

150 mg BID dexpramipexole

Arm Description

Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks.

Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks.

Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks.

Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT04046939

First Posted

July 30, 2019

Last Updated

April 11, 2023

Sponsor

Knopp Biosciences

1. Study Identification

Unique Protocol Identification Number

NCT04046939

Brief Title

Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma

Acronym

EXHALE-1

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

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Completed

Study Start Date

August 15, 2019 (Actual)

Primary Completion Date

December 3, 2020 (Actual)

Study Completion Date

March 2, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Knopp Biosciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Eosinophilic Asthma, Asthma

Keywords

Eosinophilic Asthma, Asthma, dexpramipexole

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Four-arm parallel assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

534 (Actual)

8. Arms, Groups, and Interventions

Arm Title

placebo BID

Arm Type

Placebo Comparator

Arm Description

Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks.

Arm Title

37.5 mg BID dexpramipexole

Arm Type

Active Comparator

Arm Description

Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks.

Arm Title

75 mg BID dexpramipexole

Arm Type

Active Comparator

Arm Description

Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks.

Arm Title

150 mg BID dexpramipexole

Arm Type

Active Comparator

Arm Description

Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks.

Intervention Type

Drug

Intervention Name(s)

Dexpramipexole

Other Intervention Name(s)

KNS-760704, BIIB050

Intervention Description

dexpramipexole twice daily oral dosing for up to 12 weeks

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

PBO

Intervention Description

placebo twice daily oral dosing for up to 12 weeks

Primary Outcome Measure Information:

Title

Change in Blood Absolute Eosinophil Count From Baseline to Week 12

Description

Time Frame

Baseline, 12 Weeks

Secondary Outcome Measure Information:

Title

Change in Pre-bronchodilator FEV1 (Liters) From Baseline to Week 12

Description

FEV1 is defined as the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation.

Time Frame

Baseline, 12 Weeks

Title

Change in Asthma Control Questionnaire (ACQ-6) Score From Baseline to Week 12

Description

Time Frame

Baseline, 12 Weeks

Title

Change in Post-bronchodilator FEV1 From Baseline to Week 12

Description

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.

Time Frame

Baseline, 12 Weeks

Title

Change in Quality of Life, as Measured by the Asthma Quality of Life Questionnaire (AQLQ) From Baseline to Week 12

Description

Time Frame

Baseline, 12 Weeks

Title

Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group Post Randomization Through Week 12

Description

Time Frame