A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Dexpramipexole Administered Orally for 52 Weeks in Participants With Severe Eosinophilic Asthma

Areteia Therapeutics397 sites in 1 country1,061 target enrollmentJanuary 30, 2023

ConditionsEosinophilic Asthma Asthma; Eosinophilic Asthma

InterventionsDexpramipexole Dihydrochloride Placebo

DrugsDexpramipexole Dihydrochloride Placebo

Overview

Phase: Phase 3
Intervention: Dexpramipexole Dihydrochloride
Conditions: Eosinophilic Asthma
Sponsor: Areteia Therapeutics
Enrollment: 1061
Locations: 397
Primary Endpoint: Annualized rate of severe asthma exacerbations over 52 weeks.
Status: Terminated
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study will assess the efficacy and safety of dexpramipexole as an adjunctive oral therapy in participants with inadequately controlled asthma with an eosinophilic phenotype and a history of asthma exacerbations.

Detailed Description

This is a multicenter, randomized, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of dexpramipexole in adults and adolescents with severe, inadequately controlled asthma with eosinophilic phenotype on medium to high-dose inhaled corticosteroids (ICS )and at least one additional asthma controller medication with or without oral corticosteroids (OCS). Approximately 1400 participants will be randomized globally. Participants will receive dexpramipexole, or placebo, administered orally, over a 52-week treatment period. The study also includes a post-treatment follow-up period of 4 weeks.

Registry

clinicaltrials.gov

Start Date

January 30, 2023

End Date

December 8, 2025

Last Updated

4 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Areteia Therapeutics

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Signed informed consent form and assent form, as appropriate
•Male or female ≥12 years of age at Screening Visit 1
•Asthma-related criteria
•Documented physician diagnosis of asthma for ≥12 months prior to Screening Visit
•Treatment of asthma, participants must satisfy all the below (items a to c):
•Participants who have received asthma controller medication with medium or high dose inhaled corticosteroids (ICS; ≥500 μg/day fluticasone propionate dry powder formulation daily or clinically comparable, per Global Initiative for Asthma (GINA) 2021) on a regular basis for at least 12 months prior to Screening Visit
•Documented treatment with a stable dose of either medium or high dose ICS for at least 3 months prior to Screening Visit
•The ICS may be contained within an ICS/LABA (long-acting β2 agonist) combination product. Daily oral corticosteroids are an allowed concomitant medication; participants on daily oral corticosteroids must be on a stable dose for 3 months before Screening Visit
•Use of one of more additional daily maintenance asthma controller medications according to standard practice of care is required. Use of a stable dose of any additional asthma controller medications must be documented for at least 3 months prior to Screening Visit
•Pre-bronchodilator forced expiratory volume (Pre-BD FEV₁) ≥40% and \<80% (\<90% for participants 12 to 17 years of age) of predicted at Screening Visit

Exclusion Criteria

•Asthma-related criteria
•A participant who experiences a severe asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic corticosteroids) at any time from 4 weeks prior to Screening Visit.
•Participants who experience an asthma exacerbation during the Screening/Run-in Period may remain in screening and proceed with study visits 14 days after they have completed their course of oral steroids or returned to their pre-Screening Visit maintenance dose of oral steroids and the investigator considers participant has returned to baseline status.
•Current diagnosis of diseases which may confound interpretation of this study's findings such as allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, eosinophilic gastrointestinal diseases, hypereosinophilic syndrome, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis.
•Respiratory infection: Upper or lower respiratory tract, sinus, or middle ear infection within the 4 weeks before Screening Visit
•For participants aged 12 to 17 years old, AEC of \<0.15x10⁹/L at Screening Visit
•Prohibited medications/procedures
•Treatment with a biologic investigational drug in the last 5 months prior to Screening Visit
•Treatment with non-biologic investigational drugs in the previous 30 days or five-half-lives prior to Screening Visit 1, whichever is longer. Treatment with GSK3511294 (long-acting anti-IL-5) in the past 12 months.
•Treatment with any of the following monoclonal antibody therapies within 120 days prior to Baseline Visit: benralizumab, dupilumab, mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab.

Arms & Interventions

150 mg BID

Dexpramipexole 150 mg oral tablet taken twice a day

Intervention: Dexpramipexole Dihydrochloride

75 mg BID

Dexpramipexole 75 mg oral tablet taken twice a day

Intervention: Dexpramipexole Dihydrochloride

Placebo

Placebo oral tablet taken twice a day

Intervention: Placebo

Outcomes

Primary Outcomes

Annualized rate of severe asthma exacerbations over 52 weeks.

Time Frame: Day 1 (baseline, pre-dose) through Week 52

A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for \>=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids; or death due to asthma.

Secondary Outcomes

Absolute Change in pre-bronchodilator forced expiratory volume (Pre-BD FEV)₁ from Baseline(Day 1 (baseline, pre-dose), Weeks 36, 44, 52)
Change in Standardized version of the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ+12) from baseline to Week 52.(Day 1 (baseline, pre-dose) through Week 52)
Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6)(Day 1 (baseline, pre-dose), Weeks 36, 44, 52)
Annualized rate of severe exacerbations requiring an emergency department visit or hospitalization over 52 weeks.(Day 1 (baseline, pre-dose) through Week 52)
Annualized Rate of severe exacerbations from Week 4 to Week 52(Week 4 through Week 52)
Change from baseline in forced vital capacity (FVC)(Day 1 (baseline, pre-dose), Weeks 4, 12, 20,28 36, 44, 52)
Change from baseline in peak expiratory flow (PEF)(Day 1 (baseline, pre-dose) through Week 52)
Average change in absolute eosinophil count (AEC)(Day 1 (baseline, pre-dose) Weeks 36, 44, 52)
Change from baseline in the EuroQol five-dimensional questionnaire (EQ-5D-5L)(Day 1 (baseline, pre-dose) through Week 52)
Average change from baseline in forced vital capacity (FVC)(Day 1 (baseline, pre-dose), Weeks 36, 44, 52)
Change from baseline in Post-bronchodilator FEV₁(Day 1 (baseline, pre-dose) through Week 52)
Time to first severe asthma exacerbation(Up to Week 52)
Change from baseline in total asthma symptom score(Day 1 (baseline, pre-dose) through Week 52)