A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma. (EXHALE-2)
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|ClinicalTrials.gov Identifier: NCT05763121|
Recruitment Status : Recruiting
First Posted : March 10, 2023
Last Update Posted : March 10, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Eosinophilic Asthma Asthma; Eosinophilic Asthma||Drug: Dexpramipexole Dihydrochloride Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1395 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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|
|Actual Study Start Date :||January 30, 2023|
|Estimated Primary Completion Date :||November 2025|
|Estimated Study Completion Date :||December 2025|
Experimental: 150 mg BID
Dexpramipexole 150 mg oral tablet taken twice a day
Drug: Dexpramipexole Dihydrochloride
oral administration of dexpramipexole tablet
Experimental: 75 mg BID
Dexpramipexole 75 mg oral tablet taken twice a day
Drug: Dexpramipexole Dihydrochloride
oral administration of dexpramipexole tablet
Placebo Comparator: Placebo
Placebo oral tablet taken twice a day
oral administration of placebo tablet
- Annualized rate of severe asthma exacerbations (AAER) over 52 weeks. [ Time Frame: Day 1 (baseline, pre-dose) through Week 52 ]A severe asthma exacerbation is defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic corticosteroids.
- Absolute Change in pre-bronchodilator forced expiratory volume (Pre-BD FEV)₁ from Baseline [ Time Frame: Day 1 (baseline, pre-dose), Weeks 36, 44, 52 ]The absolute change from baseline in pre-bronchodilator forced expiratory volume, averaged across visits at Weeks 36, 44, and 52.
- Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) [ Time Frame: Day 1 (baseline, pre-dose), Weeks 36, 44, 52 ]Asthma Control Questionnaire-6 (ACQ-6), change from baseline, averaged across visits at Weeks 36, 44, and 52.
- Change From Baseline in Asthma Quality of Life Questionnaire for 12 years and older (AQLQ+12) [ Time Frame: Day 1 (baseline, pre-dose) through Week 52 ]Standardized version of the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ+12) change from baseline to Week 52.
- Annualized Rate of severe exacerbations requiring an emergency department (ED) visit or hospitalization [ Time Frame: Day 1 (baseline, pre-dose) through Week 52 ]
- Annualized Rate of severe exacerbations from Week 4 to Week 52 [ Time Frame: Week 4 through Week 52 ]
- Change in absolute eosinophil count (AEC) [ Time Frame: Day 1 (baseline, pre-dose) through Week 52 ]
- Average change from baseline in forced vital capacity (FVC) [ Time Frame: Day 1 (baseline, pre-dose), Weeks 36, 44, 52 ]
- Change from baseline in forced vital capacity (FVC) [ Time Frame: Day 1 (baseline, pre-dose), Weeks 4, 12, 20,28 36, 44, 52 ]
- Change from baseline in Post-bronchodilator FEV₁ [ Time Frame: Day 1 (baseline, pre-dose) through Week 52 ]
- Change from baseline in peak expiratory flow (PEF) [ Time Frame: Day 1 (baseline, pre-dose) through Week 52 ]
- Time to first severe asthma exacerbation [ Time Frame: Up to Week 52 ]
- Change from baseline in total asthma symptom score [ Time Frame: Day 1 (baseline, pre-dose) through Week 52 ]
- Change from baseline in the EuroQol five-dimensional questionnaire (EQ-5D-5L) [ Time Frame: Day 1 (baseline, pre-dose) through Week 52 ]
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|Ages Eligible for Study:||12 Years to 99 Years (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Signed informed consent form and assent form, as appropriate
Male or female ≥12 years of age at randomization
- Documented physician diagnosis of asthma for ≥12 months.
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.
- 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/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.
- 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.
- Pre-bronchodilator forced expiratory volume (Pre-BD FEV₁) ≥40% and <80% of predicted at Screening
Variable airflow obstruction documented with at least one of the following criteria:
- Bronchodilator reversibility during screening, 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.
- Bronchodilator reversibility, using the criteria above, documented in the past 12 months.
- Peak flow variation of ≥20% over a 2-week period, documented in the past 12 months.
- Airflow variability in clinic FEV₁ ≥20% between two consecutive clinic visits, documented in the past 12 months.
- Airway hyperresponsiveness (provocative concentration causing a 20% fall in FEV₁ of methacholine <8 mg/mL) documented in the past 12 months.
- ACQ-6 ≥1.5 at Screening.
Documented history of at least two asthma exacerbations requiring treatment with systemic corticosteroids (intramuscular, intravenous, or oral) within the past 12-month period.
General medical history
- Negative urine pregnancy test for women of childbearing potential (WOCBP; after menarche) at Screening and Baseline.
WOCBP must use either of the following methods of birth control, from Screening through the End of Study Visit:
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.
Two protocol acceptable methods of contraception in tandem.
Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for ≥12 months prior to the planned date of randomization without an alternative medical cause. The following age specific requirements apply:
- 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.
- 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.
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 the Screening Visit up to and including the Baseline 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.
For participants aged 12 to 17 years old, AEC of <0.15x10⁹/L at Screening.
- Treatment with a biologic investigational drug in the last 5 months. Treatment with non-biologic investigational drugs in the previous 30 days or five-half-lives, 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: benralizumab, dupilumab, mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab.
- Treatment with pramipexole (Mirapex®) within 30 days of Baseline.
- Treatment with selected drugs known to have a substantial risk of neutropenia in the past 30 days.
Bronchial thermoplasty procedure in the past 12 months or planned during the coming year.
General medical history
- Weight <40 kg.
- Current smoking within the past year or a smoking history of >10 pack-years. Smoking includes tobacco, vaping, and/or marijuana use.
- Known or suspected alcohol or drug abuse
- Uncontrolled severe hypertension: systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite antihypertensive therapy.
- History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the 5 years prior to randomization.
- History of human immunodeficiency virus (HIV) infection or chronic infection with hepatitis B or C.
- A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent, and assent when applicable, that has not been treated with or has failed to respond to standard of care (SoC) therapy.
- Medical or other condition likely to interfere with participant's ability to undergo study procedures, adhere to visit schedule, or comply with study requirements.
- Known or suspected noncompliance with medication.
Unwillingness or inability to follow the procedures outlined in the protocol.
Clinical safety labs
- Absolute neutrophil count (ANC) <2.000x10⁹/L at screening.
- Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m² at Screening (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula for age ≥18 years at screening; using the Bedside Schwartz eGFR formula for age <18).
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 confirmed by a repeat abnormal measurement of the relevant value(s), at least 1 week apart.
- History of New York Heart Association class IV heart failure or last known left ventricular ejection fraction <25%.
- History of major adverse cardiovascular event (MACE) within 3 months prior to randomization.
- History of cardiac arrhythmia within 3 months prior baseline that is not controlled by medication or via ablation.
- History of long QT syndrome.
- Corrected QT interval by Fridericia (QTcF) interval >450 ms for males and >470 ms for females at Screening QTcF ≥480 ms for participants with bundle branch block.
Clinically important abnormalities in resting ECG that may interfere with the interpretation of QTcF interval changes at Screening, including heart rate <45 beats per minute (bpm) or >100 bpm.
- Pregnant women or women breastfeeding
- Males who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05763121
|Contact: EXHALE Recruitingfirstname.lastname@example.org|
|United States, California|
|Research Site 20001-003||Recruiting|
|West Covina, California, United States, 91790|
|United States, Florida|
|Research Site 20001-048||Recruiting|
|Aventura, Florida, United States, 33180|
|Research Site 20001-051||Not yet recruiting|
|Brandon, Florida, United States, 33511|
|Research Site 20001-067||Not yet recruiting|
|Hialeah, Florida, United States, 33016|
|Research Site US-20001-015||Recruiting|
|Kissimmee, Florida, United States, 34744|
|Research Site 20001-004||Recruiting|
|Tampa, Florida, United States, 33607|
|United States, Missouri|
|Research Site 20001-074||Recruiting|
|Saint Charles, Missouri, United States, 63301|
|United States, Oklahoma|
|Research Site US-20001-038||Recruiting|
|Edmond, Oklahoma, United States, 73034|
|Principal Investigator:||Salman Siddiqui, MD||Imperial College Healthcare NHS Trust (via Imperial Consultants)|
|Responsible Party:||Areteia Therapeutics|
|Other Study ID Numbers:||
2022-003004-33 ( EudraCT Number )
|First Posted:||March 10, 2023 Key Record Dates|
|Last Update Posted:||March 10, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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