RECRUITING

A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma (EXHALE-3)

Conditions

Eosinophilic Asthma Asthma; Eosinophilic Asthma Exacerbations Severe Asthma Dexpramipexole EXHALE Areteia EXHALE-3 Uncontrolled Asthma Asthma Attack

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The objective of this clinical study is to investigate the safety, tolerability, and efficacy of dexpramipexole in participants with inadequately controlled severe eosinophilic asthma.

Official Title

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

Quick Facts

Study Start:2023-03-27

Study Completion:2026-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05813288

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 99 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Signed informed consent form and assent form, as appropriate. 2. Male or female ≥12 years of age at Screening Visit 1. 3. Documented physician diagnosis of asthma for ≥12 months prior to Screening Visit 1. 4. Eosinophil count of ≥0.30x10⁹/L at Screening Visit 1. If the initial value is between 0.250x10⁹/L to 0.299x10⁹/L, then this may be repeated once at an unscheduled visit (prior to Screening Visit 2). 5. Treatment of asthma, participants must satisfy all the below (items a to c): 1. 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 GINA 2021) on a regular basis for at least 12 months prior to Screening Visit 1. 2. Documented treatment with a stable dose of either medium or high dose ICS for at least 3 months prior to Visit 1. The ICS may be contained within an ICS/long-acting β2 agonist (LABA) 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 1. 3. 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 1. 6. Pre-BD FEV₁ ≥40% and \<80% (\<90% for participants 12 to 17 years of age) of predicted at Screening Visit 2. 7. Variable airflow obstruction documented with at least one of the following criteria: 1. Bronchodilator reversibility at Screening Visit 2, as evidenced by ≥12% and ≥200 mL improvement in FEV₁, 15 to 30 minutes following inhalation of 400 µg (four puffs) of albuterol/salbutamol (≥12% and ≥160 mL for ages 12 to 17). Participants who do not meet the bronchodilator reversibility inclusion criterion but have ≥10% and ≥160 mL reversibility, may repeat the reversibility spirometry assessment once during the Screening period, at an unscheduled visit at least 7 days prior to baseline. 2. Bronchodilator reversibility, using the criteria above, documented in the past 24 months prior to Screening Visit 1. 3. Peak flow variation of ≥20% over a 2-week period, documented in the past 24 months prior to Screening Visit 1. 4. Airflow variability in clinic FEV₁ ≥20% between two consecutive clinic visits, documented in the past 24 months prior to Screening Visit 1. 5. Airway hyperresponsiveness (provocative concentration causing a 20% fall in FEV₁ of methacholine \<8 mg/mL) documented in the past 24 months prior to Screening Visit 1. 8. ACQ-6 ≥1.5 at Screening Visit 2. 9. Documented history of at least two asthma exacerbations requiring treatment with systemic corticosteroids (intramuscular, intravenous, or oral) within the past 12-month period prior to Screening Visit 1. 10. Negative urine pregnancy test for women of childbearing potential (WOCBP; after menarche) at the Screening and Baseline visits. 11. WOCBP must use either of the following methods of birth control, from Screening Visit 1 through the End of Study Visit: 1. A highly effective form of birth control (confirmed by the investigator). Highly effective forms of birth control include: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective Intrauterine device (IUD), IUD/intrauterine system (IUS), Levonorgestrel Intrauterine system, or oral contraceptive. * Or 2. Two protocol acceptable methods of contraception in tandem. 3. Women \<50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range. 4. Women ≥50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.	1. 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 1 up to and including the Baseline Visit. 2. 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, or lung diseases (eg, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis). 3. Respiratory infection: Upper or lower respiratory tract, sinus, or middle ear infection within the 4 weeks before Screening Visit 1. 4. Treatment with a biologic investigational drug in the last 5 months prior to Screening Visit 1. 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. 5. Treatment with any of the following monoclonal antibody therapies within 120 days prior to Baseline: benralizumab, dupilumab, mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab. 6. Treatment with pramipexole (Mirapex®) within 30 days of Baseline. 7. Treatment with selected drugs known to have a substantial risk of neutropenia in the past 30 days prior to Screening Visit 1. 8. Bronchial thermoplasty procedure in the past 12 months prior to Screening Visit 1 or planned during the coming year. 9. Weight \<40 kg at Screening Visit 1. 10. Current smoking within 12 months prior to Screening Visit 1 or a smoking history of \>10 pack-years. Smoking includes tobacco, vaping, and/or marijuana use. 11. Known or suspected alcohol or drug abuse 12. Uncontrolled severe hypertension: systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg prior to Baseline Visit despite anti-hypertensive therapy. 13. History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the 5 years prior to Baseline Visit. 14. History of human immunodeficiency virus (HIV) infection or chronic infection with hepatitis B or C. 15. A helminth parasitic infection diagnosed within 24 weeks prior Screening Visit 1 that has not been treated with or has failed to respond to standard of care (SoC) therapy. 16. Medical or other condition likely to interfere with participant's ability to undergo study procedures, adhere to visit schedule, or comply with study requirements. 17. Known or suspected noncompliance with medication. 18. Unwillingness or inability to follow the procedures outlined in the protocol. 19. Absolute neutrophil count \<2.000x10⁹/L at screening at Screening Visit 1 or Screening Visit 2. 20. Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m² at Screening Visit 2 (using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula \[Levey et al, 2009\] for age ≥18 years at screening; using the Bedside Schwartz \[Schwartz and Work, 2009\] eGFR formula for age \<18). 21. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), \>3x the upper limit of normal (ULN), or total bilirubin \>2x ULN at Screening Visit 2 confirmed by a repeat abnormal measurement of the relevant value(s), at least 1 week apart. 22. History of New York Heart Association class IV heart failure or last known left ventricular ejection fraction \<25%. 23. History of major adverse cardiovascular event (MACE) within 3 months prior to the Baseline Visit. 24. History of cardiac arrhythmia within 3 months prior to Baseline Visit that is not controlled by medication or via ablation. 25. History of long QT syndrome. 26. Corrected QT interval by Fridericia (QTcF) interval \>450 ms for males and \>470 ms for females at Screening Visit 2 or QTcF ≥480 ms for participants with bundle branch block. 27. Clinically important abnormalities in resting ECG that may interfere with the interpretation of QTcF interval changes at Screening Visit 2, including heart rate \<45 beats per minute (bpm) or \>100 bpm. 28. Pregnant women or women breastfeeding. 29. Males who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide).

Inclusion Criteria

Exclusion Criteria

1. Signed informed consent form and assent form, as appropriate.
2. Male or female ≥12 years of age at Screening Visit 1.
3. Documented physician diagnosis of asthma for ≥12 months prior to Screening Visit 1.
4. Eosinophil count of ≥0.30x10⁹/L at Screening Visit 1. If the initial value is between 0.250x10⁹/L to 0.299x10⁹/L, then this may be repeated once at an unscheduled visit (prior to Screening Visit 2).
5. Treatment of asthma, participants must satisfy all the below (items a to c):
1. 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 GINA 2021) on a regular basis for at least 12 months prior to Screening Visit 1.
2. Documented treatment with a stable dose of either medium or high dose ICS for at least 3 months prior to Visit 1. The ICS may be contained within an ICS/long-acting β2 agonist (LABA) 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 1.
3. 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 1.
6. Pre-BD FEV₁ ≥40% and \<80% (\<90% for participants 12 to 17 years of age) of predicted at Screening Visit 2.
7. Variable airflow obstruction documented with at least one of the following criteria:
1. Bronchodilator reversibility at Screening Visit 2, as evidenced by ≥12% and ≥200 mL improvement in FEV₁, 15 to 30 minutes following inhalation of 400 µg (four puffs) of albuterol/salbutamol (≥12% and ≥160 mL for ages 12 to 17). Participants who do not meet the bronchodilator reversibility inclusion criterion but have ≥10% and ≥160 mL reversibility, may repeat the reversibility spirometry assessment once during the Screening period, at an unscheduled visit at least 7 days prior to baseline.
2. Bronchodilator reversibility, using the criteria above, documented in the past 24 months prior to Screening Visit 1.
3. Peak flow variation of ≥20% over a 2-week period, documented in the past 24 months prior to Screening Visit 1.
4. Airflow variability in clinic FEV₁ ≥20% between two consecutive clinic visits, documented in the past 24 months prior to Screening Visit 1.
5. Airway hyperresponsiveness (provocative concentration causing a 20% fall in FEV₁ of methacholine \<8 mg/mL) documented in the past 24 months prior to Screening Visit 1.
8. ACQ-6 ≥1.5 at Screening Visit 2.
9. Documented history of at least two asthma exacerbations requiring treatment with systemic corticosteroids (intramuscular, intravenous, or oral) within the past 12-month period prior to Screening Visit 1.
10. Negative urine pregnancy test for women of childbearing potential (WOCBP; after menarche) at the Screening and Baseline visits.
11. WOCBP must use either of the following methods of birth control, from Screening Visit 1 through the End of Study Visit:
1. A highly effective form of birth control (confirmed by the investigator). Highly effective forms of birth control include: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective Intrauterine device (IUD), IUD/intrauterine system (IUS), Levonorgestrel Intrauterine system, or oral contraceptive.
* Or
2. Two protocol acceptable methods of contraception in tandem.
3. Women \<50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range.
4. Women ≥50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.

1. 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 1 up to and including the Baseline Visit.
2. 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, or lung diseases (eg, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis).
3. Respiratory infection: Upper or lower respiratory tract, sinus, or middle ear infection within the 4 weeks before Screening Visit 1.
4. Treatment with a biologic investigational drug in the last 5 months prior to Screening Visit 1. 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.
5. Treatment with any of the following monoclonal antibody therapies within 120 days prior to Baseline: benralizumab, dupilumab, mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab.
6. Treatment with pramipexole (Mirapex®) within 30 days of Baseline.
7. Treatment with selected drugs known to have a substantial risk of neutropenia in the past 30 days prior to Screening Visit 1.
8. Bronchial thermoplasty procedure in the past 12 months prior to Screening Visit 1 or planned during the coming year.
9. Weight \<40 kg at Screening Visit 1.
10. Current smoking within 12 months prior to Screening Visit 1 or a smoking history of \>10 pack-years. Smoking includes tobacco, vaping, and/or marijuana use.
11. Known or suspected alcohol or drug abuse
12. Uncontrolled severe hypertension: systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg prior to Baseline Visit despite anti-hypertensive therapy.
13. History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the 5 years prior to Baseline Visit.
14. History of human immunodeficiency virus (HIV) infection or chronic infection with hepatitis B or C.
15. A helminth parasitic infection diagnosed within 24 weeks prior Screening Visit 1 that has not been treated with or has failed to respond to standard of care (SoC) therapy.
16. Medical or other condition likely to interfere with participant's ability to undergo study procedures, adhere to visit schedule, or comply with study requirements.
17. Known or suspected noncompliance with medication.
18. Unwillingness or inability to follow the procedures outlined in the protocol.
19. Absolute neutrophil count \<2.000x10⁹/L at screening at Screening Visit 1 or Screening Visit 2.
20. Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m² at Screening Visit 2 (using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula \[Levey et al, 2009\] for age ≥18 years at screening; using the Bedside Schwartz \[Schwartz and Work, 2009\] eGFR formula for age \<18).
21. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), \>3x the upper limit of normal (ULN), or total bilirubin \>2x ULN at Screening Visit 2 confirmed by a repeat abnormal measurement of the relevant value(s), at least 1 week apart.
22. History of New York Heart Association class IV heart failure or last known left ventricular ejection fraction \<25%.
23. History of major adverse cardiovascular event (MACE) within 3 months prior to the Baseline Visit.
24. History of cardiac arrhythmia within 3 months prior to Baseline Visit that is not controlled by medication or via ablation.
25. History of long QT syndrome.
26. Corrected QT interval by Fridericia (QTcF) interval \>450 ms for males and \>470 ms for females at Screening Visit 2 or QTcF ≥480 ms for participants with bundle branch block.
27. Clinically important abnormalities in resting ECG that may interfere with the interpretation of QTcF interval changes at Screening Visit 2, including heart rate \<45 beats per minute (bpm) or \>100 bpm.
28. Pregnant women or women breastfeeding.
29. Males who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide).

Contacts and Locations

Study Contact

EXHALE Recruiting

CONTACT

888-584-9281

clinicaltrials@areteiatx.com

Principal Investigator

Michael E. Wechsler, MD

PRINCIPAL_INVESTIGATOR

National Jewish Health

Study Locations (Sites)

Research Site 30001-287

Mobile, Alabama, 36608

United States

Research Site 30001-010

Little Rock, Arkansas, 72212

United States

Research Site 30001-305

Valencia, California, 97355

United States

Research Site 30001-291

Jacksonville, Florida, 32216

United States

Research Site 30001-318

Maitland, Florida, 32751

United States

Research Site 30001-311

Miami, Florida, 33144

United States

Research Site 30001-288

Miami, Florida, 33165

United States

Research Site 30001-310

Miami, Florida, 33165

United States

Research Site 30001-331

Miami, Florida, 33165

United States

Research Site 30001-082

Miami, Florida, 33179

United States

Research Site 30001-301

Naples, Florida, 34103

United States

Research Site 30001-348

Ocala, Florida, 34471

United States

Research Site 30001-331

Orlando, Florida, 32807

United States

Research Site 30001-293

Orlando, Florida, 32819

United States

Research Site 30001-312

Pembroke Pines, Florida, 33026

United States

Research Site 30001-319

Viera, Florida, 32940

United States

Research Site 30001-366

Lilburn, Georgia, 30047

United States

Research Site 30001-286

Lafayette, Louisiana, 70508

United States

Research Site 30001-313

Marrero, Louisiana, 70072

United States

Research Site 30001-372

Warren, Michigan, 48088

United States

Research Site 30001-363

Edison, New Jersey, 08817

United States

Research Site 30001-300

Schenectady, New York, 12304

United States

Research Site 30001-334

Allen, Texas, 60607

United States

Research Site 30001-090

Austin, Texas, 78726

United States

Research Site 30001-290

Austin, Texas, 78726

United States

Research Site 30001-299

Houston, Texas, 77063

United States

Research Site 30001-315

Katy, Texas, 77494

United States

Research Site 30001-295

McKinney, Texas, 75069

United States

Research Site 30001-373

Mesquite, Texas, 75150

United States

Research Site 30001-297

Pearland, Texas, 77584

United States

Research Site 30001-238

San Antonio, Texas, 78258

United States

Research Site 30001-377

San Antonio, Texas, 78258

United States

Research Site 30001-335

Sugar Land, Texas, 77479

United States

Research Site 30001-333

Pleasant View, Utah, 84404

United States

Collaborators and Investigators

Sponsor: Areteia Therapeutics

Michael E. Wechsler, MD, PRINCIPAL_INVESTIGATOR, National Jewish Health

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-03-27

Study Completion Date2026-07

Study Record Updates

Study Start Date2023-03-27

Study Completion Date2026-07

Terms related to this study

Keywords Provided by Researchers

Exacerbations
Severe Asthma
Dexpramipexole
EXHALE
Areteia
EXHALE-3
Uncontrolled Asthma
Asthma Attack

Additional Relevant MeSH Terms

Eosinophilic Asthma
Asthma; Eosinophilic
Asthma