TERMINATED

A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma.

Conditions

Eosinophilic Asthma Asthma; Eosinophilic Asthma Exacerbations Severe Asthma Dexpramipexole EXHALE Areteia EXHALE-2 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

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.

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:2023-01-30

Study Completion:2025-12-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:TERMINATED

Study ID

NCT05763121

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. 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 Global Initiative for Asthma (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 Screening Visit 1. 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 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. 5. 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 2. 6. 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 to17). 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 past 24 months prior to Screening Visit 1. 7. ACQ-6 ≥1.5 at Screening Visit 2. 8. 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. 9. Negative urine pregnancy test for women of childbearing potential (WOCBP; after menarche) at the Screening Visit 2 and Baseline Visit. 10. 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. 2. Two protocol acceptable methods of contraception in tandem. 3. Women \<50 years old would 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 would 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. 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, 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. For participants aged 12 to 17 years old, AEC of \<0.15x10⁹/L at Screening Visit 1. 5. 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. 6. Treatment with any of the following monoclonal antibody therapies within 120 days prior to Baseline Visit: benralizumab, dupilumab, mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab. 7. Treatment with pramipexole (Mirapex®) within 30 days of Baseline Visit. 8. Treatment with selected drugs known to have a substantial risk of neutropenia in the past 30 days prior to Screening Visit 1. 9. Bronchial thermoplasty procedure in the past 12 months prior to Screening Visit 1 or planned during the coming year. 10. Weight \<40 kg at Screening Visit 2. 11. Current smoking within the 12 months prior to Screening Visit 1 or a smoking history of \>10 pack-years. Smoking includes tobacco, vaping, and/or marijuana use. 12. Known or suspected alcohol or drug abuse 13. Uncontrolled severe hypertension: systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg prior to the Baseline Visit despite antihypertensive therapy. 14. History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the 5 years prior to the Baseline Visit. 15. History of human immunodeficiency virus (HIV) infection or chronic infection with hepatitis B or C. 16. A helminth parasitic infection diagnosed within 24 weeks prior to Screening Visit 1 that has not been treated with or has failed to respond to standard of care (SoC) therapy. 17. Medical or other condition likely to interfere with participant's ability to undergo study procedures, adhere to visit schedule, or comply with study requirements. 18. Known or suspected noncompliance with medication. 19. Unwillingness or inability to follow the procedures outlined in the protocol. 20. Absolute neutrophil count (ANC) \<2.000x10⁹/L at Screening Visit 1 or Screening Visit 2. 21. 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 for age ≥18 years at screening; using the Bedside Schwartz eGFR formula). 22. 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. 23. History of New York Heart Association class IV heart failure or last known left ventricular ejection fraction \<25%. 24. History of major adverse cardiovascular event (MACE) within 3 months prior to the Baseline Visit. 25. History of cardiac arrhythmia within 3 months prior to the Baseline Visit that is not controlled by medication or via ablation. 26. History of long QT syndrome. 27. 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. 28. 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. 29. Pregnant women or women breastfeeding 30. 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. 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 Global Initiative for Asthma (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 Screening Visit 1. 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 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.
5. 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 2.
6. 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 to17). 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 past 24 months prior to Screening Visit 1.
7. ACQ-6 ≥1.5 at Screening Visit 2.
8. 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.
9. Negative urine pregnancy test for women of childbearing potential (WOCBP; after menarche) at the Screening Visit 2 and Baseline Visit.
10. 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.
2. Two protocol acceptable methods of contraception in tandem.
3. Women \<50 years old would 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 would 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.
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, 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. For participants aged 12 to 17 years old, AEC of \<0.15x10⁹/L at Screening Visit 1.
5. 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.
6. Treatment with any of the following monoclonal antibody therapies within 120 days prior to Baseline Visit: benralizumab, dupilumab, mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab.
7. Treatment with pramipexole (Mirapex®) within 30 days of Baseline Visit.
8. Treatment with selected drugs known to have a substantial risk of neutropenia in the past 30 days prior to Screening Visit 1.
9. Bronchial thermoplasty procedure in the past 12 months prior to Screening Visit 1 or planned during the coming year.
10. Weight \<40 kg at Screening Visit 2.
11. Current smoking within the 12 months prior to Screening Visit 1 or a smoking history of \>10 pack-years. Smoking includes tobacco, vaping, and/or marijuana use.
12. Known or suspected alcohol or drug abuse
13. Uncontrolled severe hypertension: systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg prior to the Baseline Visit despite antihypertensive therapy.
14. History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the 5 years prior to the Baseline Visit.
15. History of human immunodeficiency virus (HIV) infection or chronic infection with hepatitis B or C.
16. A helminth parasitic infection diagnosed within 24 weeks prior to Screening Visit 1 that has not been treated with or has failed to respond to standard of care (SoC) therapy.
17. Medical or other condition likely to interfere with participant's ability to undergo study procedures, adhere to visit schedule, or comply with study requirements.
18. Known or suspected noncompliance with medication.
19. Unwillingness or inability to follow the procedures outlined in the protocol.
20. Absolute neutrophil count (ANC) \<2.000x10⁹/L at Screening Visit 1 or Screening Visit 2.
21. 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 for age ≥18 years at screening; using the Bedside Schwartz eGFR formula).
22. 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.
23. History of New York Heart Association class IV heart failure or last known left ventricular ejection fraction \<25%.
24. History of major adverse cardiovascular event (MACE) within 3 months prior to the Baseline Visit.
25. History of cardiac arrhythmia within 3 months prior to the Baseline Visit that is not controlled by medication or via ablation.
26. History of long QT syndrome.
27. 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.
28. 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.
29. Pregnant women or women breastfeeding
30. Males who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide).

Contacts and Locations

Principal Investigator

Salman Siddiqui, MD

PRINCIPAL_INVESTIGATOR

Imperial College Healthcare NHS Trust (via Imperial Consultants)

Study Locations (Sites)

Research Site 20001-374

Bakersfield, California, 93301

United States

Research Site 20001-440

La Palma, California, 90623

United States

Research Site 20001-062

Newport Beach, California, 92660

United States

Research Site 20001-043

Newport Beach, California, 92663

United States

Research Site 20001-380

Redding, California, 96001

United States

Research Site US-20001-488

San Diego, California, 92108

United States

Research Site 20001-003

West Covina, California, 91790

United States

Research Site 20001-419

Westminster, California, 92683

United States

Research Site 20001-048

Aventura, Florida, 33180

United States

Research Site 20001-005

Brandon, Florida, 33511

United States

Research Site 20001-051

Brandon, Florida, 33511

United States

Research Site 20001-029

Coral Gables, Florida, 33134

United States

Research Site 20001-350

Gainesville, Florida, 32607

United States

Research Site 20001-014

Green Acres, Florida, 33467

United States

Research Site 20001-054

Hialeah, Florida, 33012

United States

Research Site 20001-067

Hialeah, Florida, 33016

United States

Research Site 20001-020

Homestead, Florida, 33030

United States

Research Site 20001-015

Kissimmee, Florida, 34744

United States

Research Site 20001-002

Kissimmee, Florida, 34746

United States

Research Site 20001-086

Loxahatchee Groves, Florida, 33470

United States

Research Site 20001-066

Miami, Florida, 33126

United States

Research Site 20001-001

Miami, Florida, 33135

United States

Research Site 20001-059

Miami, Florida, 33144

United States

Research Site 20001-026

Miami, Florida, 33155

United States

Research Site 20001-065

Miami, Florida, 33173

United States

Research Site 20001-024

Miami, Florida, 33184

United States

Research Site 20001-069

St. Petersburg, Florida, 33713

United States

Research Site 20001-004

Tampa, Florida, 33607

United States

Research Site 20001-075

Augusta, Georgia, 30909

United States

Research Site 20001-018

Columbus, Georgia, 31904

United States

Research Site 20001-459

Sugar Hill, Georgia, 30518

United States

Research Site 20001-090

Berwyn, Illinois, 60402

United States

Research Site 20001-476

Chicago, Illinois, 60611

United States

Research Site 20001-358

Normal, Illinois, 61761

United States

Research Site 20001-135

River Forest, Illinois, 60305

United States

Research Site 20001-403

Skokie, Illinois, 60077

United States

Research Site 20001-036

Elwood, Indiana, 46036

United States

Research Site 20001-044

Evansville, Indiana, 47715

United States

Research Site 20001-021

Iowa City, Iowa, 52242

United States

Research Site 20001-019

Owensboro, Kentucky, 42301

United States

Research Site 20001-466

Baltimore, Maryland, 21237

United States

Research Site 20001-456

Takoma Park, Maryland, 20912

United States

Research Site 20001-055

White Marsh, Maryland, 21162

United States

Research Site 20001-468

Fall River, Massachusetts, 02723

United States

Research Site 20001-006

Flint, Michigan, 48504

United States

Research Site 20001-148

Flint, Michigan, 48507

United States

Research Site 20001-463

Rochester Hills, Michigan, 48307

United States

Research Site 20001-370

Chesterfield, Missouri, 63005

United States

Research Site 20001-074

Saint Charles, Missouri, 63301

United States

Research Site 20001-046

St Louis, Missouri, 63110

United States

Research Site 20001-409

Missoula, Montana, 59808

United States

Research Site 20001-486

Henderson, Nevada, 89052

United States

Research Site 20001-473

Las Vegas, Nevada, 89109

United States

Research Site 20001-471

Highland Park, New Jersey, 08904

United States

Research Site 20001-457

Jersey City, New Jersey, 07304

United States

Research Site 20001-420

New Brunswick, New Jersey, 08901

United States

Research Site 20001-050

East Amherst, New York, 14051

United States

Research Site 20001-047

Hawthorne, New York, 10532

United States

Research Site 20001-422

Rochester, New York, 14607

United States

Research Site 20001-368

The Bronx, New York, 10455

United States

Research Site 20001-408

Charlotte, North Carolina, 28273

United States

Research Site 20001-039

Gastonia, North Carolina, 28054

United States

Research Site 20001-435

Greenville, North Carolina, 27834

United States

Research Site 20001-382

Raleigh, North Carolina, 27610

United States

Research Site 20001-034

Cincinnati, Ohio, 45215

United States

Research Site 20001-013

Cincinnati, Ohio, 45219

United States

Research Site 20001-017

Dayton, Ohio, 45424

United States

Research Site 20001-063

Toledo, Ohio, 43617

United States

Research Site 20001-038

Edmond, Oklahoma, 73034

United States

Research Site 20001-079

Oklahoma City, Oklahoma, 73120

United States

Research Site 20001-395

Hershey, Pennsylvania, 17033

United States

Research Site 20001-032

Columbia, South Carolina, 29204

United States

Research Site 20001-025

Greenville, South Carolina, 29615

United States

Research Site 20001-073

Spartanburg, South Carolina, 29303

United States

Research Site 20001-438

Dickson, Tennessee, 37055

United States

Research Site 20001-068

Amarillo, Texas, 79124

United States

Research Site 20001-023

Dallas, Texas, 75230

United States

Research Site 20001-028

Dallas, Texas, 75235

United States

Research Site 20001-064

Houston, Texas, 77074

United States

Research Site 20001-085

Houston, Texas, 77099

United States

Research Site 20001-478

Plano, Texas, 75093

United States

Research Site 20001-072

The Woodlands, Texas, 77380

United States

Research Site 20001-258

Murray, Utah, 84107

United States

Research Site 20001-477

Salt Lake City, Utah, 84107

United States

Research Site 20001-340

Burke, Virginia, 22015

United States

Research Site 20001-479

Vienna, Virginia, 22180

United States

Research Site 20001-480

Barboursville, West Virginia, 25504

United States

Research Site 20001-433

La Crosse, Wisconsin, 54601

United States

Research Site 20001-057

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: Areteia Therapeutics

Salman Siddiqui, MD, PRINCIPAL_INVESTIGATOR, Imperial College Healthcare NHS Trust (via Imperial Consultants)

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 Date2023-01-30

Study Completion Date2025-12-08

Study Record Updates

Study Start Date2023-01-30

Study Completion Date2025-12-08

Terms related to this study

Keywords Provided by Researchers

Exacerbations
Severe Asthma
Dexpramipexole
EXHALE
Areteia
EXHALE-2
Uncontrolled Asthma
Asthma Attack

Additional Relevant MeSH Terms

Eosinophilic Asthma
Asthma; Eosinophilic
Asthma