Clinical Trials List
Protocol NumberAR-DEX-22-02
Completed
2023-10-16 - 2027-06-30
Phase III
Recruiting11
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 (EXHALE-3)
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Trial Applicant
WORLDWIDE CLINICAL TRIALS (TAIWAN) CO., LTD.
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Sponsor
Areteia Therapeutics, Inc
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 余文光 無
- 陳燕溫 無
- 潘聖衛 無
- 張芝榕 Division of Thoracic Medicine
- 孫傳硯 無
- 林芳綺 無
- Jia-Yih Feng 無
- Kang-Cheng Su 無
- 周昆達 無
- KUANG-YAO YANG 無
- 蕭慈慧 無
- 沈曉津 無
- D.W. Peng 無
- 蕭逸函 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Wei-An Chang 無
- Ming-Ju Tsai 無
- Hung-Ling Huang 無
- 陳家閔 Division of Thoracic Medicine
- 鄭孟軒 無
- 莊政皓 無
- 鄭至宏 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chin-Wei Kuo 無
- 林建佑 無
- 林偉傑 無
- 陳炯睿 無
- Chang-Wen Chen 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Po-Hao Feng
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
severe eosinophilic asthma (EXHALE-3)
Objectives
To demonstrate the efficacy of dexpramipexole in reducing severe asthma
exacerbations.
Test Drug
tablets
Active Ingredient
Dexpramipexole
Dosage Form
110
Dosage
75 / 150 mg
Endpoints
Annualized rate of severe asthma exacerbations (AAER) over 52 weeks.
Inclution Criteria
1. Willing to sign the informed consent form and consent form.
2. Male or female aged 18 years or older at the first screening clinic.
Asthma-related criteria
3. Having a physician's diagnosis and record of asthma for ≥12 months prior to the first screening clinic.
4. Eosinophil count ≥0.30 x 10⁹/L at the first screening clinic. If the initial value is between 0.250 x 10⁹/L and 0.299 x 10⁹/L, it can be repeated once at an unscheduled clinic (before the second screening clinic).
5. Asthma Treatment: Subjects must meet all of the following criteria (items a through c):
a. For at least 12 months prior to the first screening outpatient visit, subjects must have been regularly taking asthma control medication, using a moderate or high dose of inhaled corticosteroids (ICS; ≥500 μg/day of fluticasone propionate dry powder, or a clinically equivalent dry powder according to GINA 2021). Equivalent moderate and high dose ICS dosages are detailed in Appendix C.
b. For at least 3 months prior to the first screening outpatient visit, subjects must have been treated with a stable and documented moderate or high dose of ICS. ICS may be included in an ICS/long-acting β2 agonist (LABA) combination product. As described in Section 5.2.2, daily oral corticosteroids are an approved concomitant medication; subjects taking daily oral corticosteroids must have been on a stable dose for at least 3 months prior to the first screening outpatient visit.
c. One or more additional daily maintenance asthma control medications must be used according to standard care practice;
e.g., LABA, leukotriene blockers, theophylline, long-acting creatine blockers, cromolyn/nedocromil. If a stable dose of any additional asthma control medication is used, it must have been recorded for at least 3 months prior to the first screening outpatient visit.
6. At the second screening outpatient visit, FEV1 before BD is ≥40% and <80% compared to predicted values.
7. Variable airflow obstruction records meet at least one of the following criteria:
a. At the second screening outpatient visit, bronchodilator reversibility is demonstrated by: 15 to 30 minutes after inhaling 400 ug (4 aspirations) of albuterol/salbutamol, an improvement in FEV1 of ≥12% and ≥200 mL. a. Those who do not meet the inclusion criteria for bronchodilator reversibility but possess ≥10% and ≥160 mL reversibility may have a reversible vital capacity assessment repeated during the screening period at an outpatient visit at least 7 days prior to the baseline period.
b. Those with a bronchodilator reversibility meeting the above criteria recorded within the past 24 months before or during the first screening visit.
c. Those with a peak expiratory flow rate variation of ≥20% over more than two cycles recorded within the past 24 months before or during the first screening visit.
d. Those with a clinical FEV1 airflow variability of ≥20% between two consecutive clinical visits recorded within the past 24 months before or during the first screening visit. e. Documented airway hyperresponsiveness within 24 months prior to the first screening clinic visit (a 20% decrease in FEV1 at a provocation concentration of methacholine <8 mg/mL, or other clinically relevant bronchial provocation tests).
8. ACQ-6 ≥1.5 at the second screening clinic visit.
9. Documented history of at least two acute asthma attacks requiring systemic corticosteroid treatment (intramuscular, intravenous, or oral) within 24 months prior to the first screening clinic visit.
General Medical History
10. Negative urine pregnancy test for women of childbearing potential (WOCBP; postmenopausal) at both the screening and baseline clinic visits.
11. WOCBP (postmenopausal) must use one of the following methods of contraception from the first screening clinic visit until the end of the study visit:
a. A highly effective method of contraception (confirmed by the study administrator). Highly effective methods of contraception include: true abstinence, a vasectomy in the partner, an in-arm implantable device, female sterilization through tubal occlusion, any effective intrauterine device (IUD), intrauterine device/intrauterine system (IUS), emergency contraception (IUS), or oral contraceptives.
Or
b. Using two methods of contraception acceptable in the plan simultaneously.
Women who are infertile are defined as permanently sterilized women (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or postmenopausal women. Postmenopausal women are considered to have missed menstruation for ≥12 months prior to their base period outpatient appointment without other medical reasons.
The following age-specific requirements apply:
c. Women under 50 years of age are considered postmenopausal if they have missed menstruation for 12 months or more after discontinuation of exogenous hormone therapy and their follicle-stimulating hormone (FSH) levels are within the postmenopausal range.
d. Women aged 50 and above will be considered postmenopausal if they have been menopausal for 12 months or more after all exogenous hormone therapy has been discontinued.
2. Male or female aged 18 years or older at the first screening clinic.
Asthma-related criteria
3. Having a physician's diagnosis and record of asthma for ≥12 months prior to the first screening clinic.
4. Eosinophil count ≥0.30 x 10⁹/L at the first screening clinic. If the initial value is between 0.250 x 10⁹/L and 0.299 x 10⁹/L, it can be repeated once at an unscheduled clinic (before the second screening clinic).
5. Asthma Treatment: Subjects must meet all of the following criteria (items a through c):
a. For at least 12 months prior to the first screening outpatient visit, subjects must have been regularly taking asthma control medication, using a moderate or high dose of inhaled corticosteroids (ICS; ≥500 μg/day of fluticasone propionate dry powder, or a clinically equivalent dry powder according to GINA 2021). Equivalent moderate and high dose ICS dosages are detailed in Appendix C.
b. For at least 3 months prior to the first screening outpatient visit, subjects must have been treated with a stable and documented moderate or high dose of ICS. ICS may be included in an ICS/long-acting β2 agonist (LABA) combination product. As described in Section 5.2.2, daily oral corticosteroids are an approved concomitant medication; subjects taking daily oral corticosteroids must have been on a stable dose for at least 3 months prior to the first screening outpatient visit.
c. One or more additional daily maintenance asthma control medications must be used according to standard care practice;
e.g., LABA, leukotriene blockers, theophylline, long-acting creatine blockers, cromolyn/nedocromil. If a stable dose of any additional asthma control medication is used, it must have been recorded for at least 3 months prior to the first screening outpatient visit.
6. At the second screening outpatient visit, FEV1 before BD is ≥40% and <80% compared to predicted values.
7. Variable airflow obstruction records meet at least one of the following criteria:
a. At the second screening outpatient visit, bronchodilator reversibility is demonstrated by: 15 to 30 minutes after inhaling 400 ug (4 aspirations) of albuterol/salbutamol, an improvement in FEV1 of ≥12% and ≥200 mL. a. Those who do not meet the inclusion criteria for bronchodilator reversibility but possess ≥10% and ≥160 mL reversibility may have a reversible vital capacity assessment repeated during the screening period at an outpatient visit at least 7 days prior to the baseline period.
b. Those with a bronchodilator reversibility meeting the above criteria recorded within the past 24 months before or during the first screening visit.
c. Those with a peak expiratory flow rate variation of ≥20% over more than two cycles recorded within the past 24 months before or during the first screening visit.
d. Those with a clinical FEV1 airflow variability of ≥20% between two consecutive clinical visits recorded within the past 24 months before or during the first screening visit. e. Documented airway hyperresponsiveness within 24 months prior to the first screening clinic visit (a 20% decrease in FEV1 at a provocation concentration of methacholine <8 mg/mL, or other clinically relevant bronchial provocation tests).
8. ACQ-6 ≥1.5 at the second screening clinic visit.
9. Documented history of at least two acute asthma attacks requiring systemic corticosteroid treatment (intramuscular, intravenous, or oral) within 24 months prior to the first screening clinic visit.
General Medical History
10. Negative urine pregnancy test for women of childbearing potential (WOCBP; postmenopausal) at both the screening and baseline clinic visits.
11. WOCBP (postmenopausal) must use one of the following methods of contraception from the first screening clinic visit until the end of the study visit:
a. A highly effective method of contraception (confirmed by the study administrator). Highly effective methods of contraception include: true abstinence, a vasectomy in the partner, an in-arm implantable device, female sterilization through tubal occlusion, any effective intrauterine device (IUD), intrauterine device/intrauterine system (IUS), emergency contraception (IUS), or oral contraceptives.
Or
b. Using two methods of contraception acceptable in the plan simultaneously.
Women who are infertile are defined as permanently sterilized women (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or postmenopausal women. Postmenopausal women are considered to have missed menstruation for ≥12 months prior to their base period outpatient appointment without other medical reasons.
The following age-specific requirements apply:
c. Women under 50 years of age are considered postmenopausal if they have missed menstruation for 12 months or more after discontinuation of exogenous hormone therapy and their follicle-stimulating hormone (FSH) levels are within the postmenopausal range.
d. Women aged 50 and above will be considered postmenopausal if they have been menopausal for 12 months or more after all exogenous hormone therapy has been discontinued.
Exclusion Criteria
Candidates will be excluded from the study if any of the following exclusion criteria are met at the first screening clinic, or at the time point specified by the individual criteria below: Asthma-Related Criteria
1. Any participant who experiences a severe acute asthma attack (defined as an asthma exacerbation leading to emergency treatment, hospitalization for asthma, or systemic corticosteroid treatment) at any time within 4 weeks prior to the first screening clinic. Participants experiencing an acute asthma attack during the screening/safety trial period may remain in the screening phase and continue attending the study clinic, but must complete their oral steroid treatment for 14 days or resume the maintenance dose of oral steroids from the pre-screening clinic, and be deemed by the trial administrator to have returned to baseline status.
2. Current medical diagnoses may confound the interpretation of the study results, such as allergic bronchopulmonary aspergillosis, eosinophilic granuloma with polyangiitis, eosinophilic gastrointestinal disease, eosinophilic leukocytosis syndrome, or lung disease (e.g., chronic obstructive pulmonary disease, spontaneous pulmonary fibrosis).
3. Respiratory tract infection: Upper or lower respiratory tract, sinus, or middle ear infection within 4 weeks prior to the first screening clinic visit.
Contraindicated Drugs/Treatment
4. Treatment with a biological investigational drug within 5 months prior to the first screening clinic visit. Treatment with a non-biological investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first screening clinic visit. Treatment with GSK3511294 (long-acting anti-interleukin [IL]-5) within the past 12 months.
5. Treatment with any of the following monoclonal antibodies within 120 days prior to the baseline period: benralizumab, dupilumab, mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab.
6. Treatment with pramipexole (Mirapex®) within 30 days of the baseline period.
7. Treatment with a selected medication known to carry a substantial risk of neutropenia within 30 days prior to the first screening outpatient visit (see Appendix A).
8. Bronchial thermoplastic surgery performed within 12 months prior to the first screening outpatient visit, or planned to perform it within the next year.
General Medical History
9. Weight less than 40 kg at the first screening outpatient visit.
10. Smoker within 12 months prior to the first screening outpatient visit, or with a smoking history of more than 10 pack-years. Smoking includes tobacco, e-cigarettes, and/or cannabis use.
11. Known or suspected alcohol or drug abuse.
12. Poorly controlled severe hypertension: Systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg prior to the baseline outpatient visit, even with existing antihypertensive treatment.
13. A history of surgery (excluding local and extensive excision), radiation therapy, and/or systemic treatment due to malignancy within the 5 years prior to the baseline outpatient visit.
14. A history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C infection.
15. A diagnosis of helminthic parasitic infection within 24 weeks prior to the first screening outpatient visit, without receiving standard care (SoC) treatment or with ineffective SoC treatment.
16. Medical or other circumstances that may interfere with the subject's ability to perform study procedures, adhere to outpatient schedules, or comply with study requirements.
17. Known or suspected non-compliance with medication.
18. Unwillingness or inability to follow the procedures outlined in the trial protocol.
Laboratory Clinical Safety
19. An absolute neutrophil count <2.000 x 10^9/L at the first or second screening outpatient visit.
20. Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² at the second screening outpatient visit (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula).
21. Active liver disease defined as any known infectious, neoplastic, or metabolic liver pathology, or, at the second screening outpatient visit, an unexplained elevation of alanine transaminase (ALT) or aspartate transaminase (AST) to more than 3 times the upper limit of normal (ULN), or an unexplained elevation of total bilirubin to more than 2 times the upper limit of normal (ULN), confirmed by repeated abnormal measurements of the relevant values at least 1 week later.
Cardiac Safety
22. History of New York Heart Association grade IV heart failure or last known left ventricular ejection ratio <25%.
23. History of a major adverse cardiovascular event (MACE) within 3 months prior to the baseline outpatient visit. 24. History of arrhythmia within 3 months prior to the baseline outpatient visit, without medication or stripping control.
25. Long-term history of QT syndrome.
26. At the second screening outpatient visit, the corrected QT interval Fridericia (QTcF) interval was >450 ms for men and >470 ms for women; for subjects with bundle branch block, it was ≥480 ms.
27. Clinically significant resting ECG abnormalities that may interfere with the interpretation of QTcF interval changes at the second screening outpatient visit, including resting heart rate (bpm) below 45 or above 100.
Pregnancy/Lactation
28. Pregnant or lactating women.
29. Men who were unwilling to use an acceptable method of contraception (i.e., condoms with spermicide) throughout the study period.
Allergic/Hypersensitivity Reactions
30. Allergic or hypersensitivity reactions to dexpramipexole or any of its components.
For this study, rescreening is permitted only under specific circumstances and after consultation with the trial sponsor's clinical representative. The screening period may be extended after consultation with the medical monitor or the trial sponsor's clinical representative (e.g., to resolve logistical or technical issues). Furthermore, the trial principal investigator and the medical monitor/trial sponsor may decide to rescreen at their discretion after the resolution of mild comorbidities. Otherwise, individuals who do not qualify for participation in this study (failed screening) may not be rescreened.
If rescreening is required, consent must be re-agreed, and all screening procedures must be repeated. A new screening number will be assigned to the participant. Participants must be confirmed to meet all eligibility criteria for the new screening number and procedures before proceeding to randomization/Day 1.
The screening period may be extended after consultation with the medical monitor or the trial sponsor's clinical representative (e.g., to resolve logistical or technical issues).
1. Any participant who experiences a severe acute asthma attack (defined as an asthma exacerbation leading to emergency treatment, hospitalization for asthma, or systemic corticosteroid treatment) at any time within 4 weeks prior to the first screening clinic. Participants experiencing an acute asthma attack during the screening/safety trial period may remain in the screening phase and continue attending the study clinic, but must complete their oral steroid treatment for 14 days or resume the maintenance dose of oral steroids from the pre-screening clinic, and be deemed by the trial administrator to have returned to baseline status.
2. Current medical diagnoses may confound the interpretation of the study results, such as allergic bronchopulmonary aspergillosis, eosinophilic granuloma with polyangiitis, eosinophilic gastrointestinal disease, eosinophilic leukocytosis syndrome, or lung disease (e.g., chronic obstructive pulmonary disease, spontaneous pulmonary fibrosis).
3. Respiratory tract infection: Upper or lower respiratory tract, sinus, or middle ear infection within 4 weeks prior to the first screening clinic visit.
Contraindicated Drugs/Treatment
4. Treatment with a biological investigational drug within 5 months prior to the first screening clinic visit. Treatment with a non-biological investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first screening clinic visit. Treatment with GSK3511294 (long-acting anti-interleukin [IL]-5) within the past 12 months.
5. Treatment with any of the following monoclonal antibodies within 120 days prior to the baseline period: benralizumab, dupilumab, mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab.
6. Treatment with pramipexole (Mirapex®) within 30 days of the baseline period.
7. Treatment with a selected medication known to carry a substantial risk of neutropenia within 30 days prior to the first screening outpatient visit (see Appendix A).
8. Bronchial thermoplastic surgery performed within 12 months prior to the first screening outpatient visit, or planned to perform it within the next year.
General Medical History
9. Weight less than 40 kg at the first screening outpatient visit.
10. Smoker within 12 months prior to the first screening outpatient visit, or with a smoking history of more than 10 pack-years. Smoking includes tobacco, e-cigarettes, and/or cannabis use.
11. Known or suspected alcohol or drug abuse.
12. Poorly controlled severe hypertension: Systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg prior to the baseline outpatient visit, even with existing antihypertensive treatment.
13. A history of surgery (excluding local and extensive excision), radiation therapy, and/or systemic treatment due to malignancy within the 5 years prior to the baseline outpatient visit.
14. A history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C infection.
15. A diagnosis of helminthic parasitic infection within 24 weeks prior to the first screening outpatient visit, without receiving standard care (SoC) treatment or with ineffective SoC treatment.
16. Medical or other circumstances that may interfere with the subject's ability to perform study procedures, adhere to outpatient schedules, or comply with study requirements.
17. Known or suspected non-compliance with medication.
18. Unwillingness or inability to follow the procedures outlined in the trial protocol.
Laboratory Clinical Safety
19. An absolute neutrophil count <2.000 x 10^9/L at the first or second screening outpatient visit.
20. Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² at the second screening outpatient visit (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula).
21. Active liver disease defined as any known infectious, neoplastic, or metabolic liver pathology, or, at the second screening outpatient visit, an unexplained elevation of alanine transaminase (ALT) or aspartate transaminase (AST) to more than 3 times the upper limit of normal (ULN), or an unexplained elevation of total bilirubin to more than 2 times the upper limit of normal (ULN), confirmed by repeated abnormal measurements of the relevant values at least 1 week later.
Cardiac Safety
22. History of New York Heart Association grade IV heart failure or last known left ventricular ejection ratio <25%.
23. History of a major adverse cardiovascular event (MACE) within 3 months prior to the baseline outpatient visit. 24. History of arrhythmia within 3 months prior to the baseline outpatient visit, without medication or stripping control.
25. Long-term history of QT syndrome.
26. At the second screening outpatient visit, the corrected QT interval Fridericia (QTcF) interval was >450 ms for men and >470 ms for women; for subjects with bundle branch block, it was ≥480 ms.
27. Clinically significant resting ECG abnormalities that may interfere with the interpretation of QTcF interval changes at the second screening outpatient visit, including resting heart rate (bpm) below 45 or above 100.
Pregnancy/Lactation
28. Pregnant or lactating women.
29. Men who were unwilling to use an acceptable method of contraception (i.e., condoms with spermicide) throughout the study period.
Allergic/Hypersensitivity Reactions
30. Allergic or hypersensitivity reactions to dexpramipexole or any of its components.
For this study, rescreening is permitted only under specific circumstances and after consultation with the trial sponsor's clinical representative. The screening period may be extended after consultation with the medical monitor or the trial sponsor's clinical representative (e.g., to resolve logistical or technical issues). Furthermore, the trial principal investigator and the medical monitor/trial sponsor may decide to rescreen at their discretion after the resolution of mild comorbidities. Otherwise, individuals who do not qualify for participation in this study (failed screening) may not be rescreened.
If rescreening is required, consent must be re-agreed, and all screening procedures must be repeated. A new screening number will be assigned to the participant. Participants must be confirmed to meet all eligibility criteria for the new screening number and procedures before proceeding to randomization/Day 1.
The screening period may be extended after consultation with the medical monitor or the trial sponsor's clinical representative (e.g., to resolve logistical or technical issues).
The Estimated Number of Participants
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Taiwan
40 participants
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Global
930 participants
