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

Inclusion Criteria: 1. Signed informed consent form and assent form, as appropriate. 2. Male or female ≥12 years of age at Screening Visit 1. Asthma-related criteria 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 or during Screening. 3. Peak flow variation of ≥20% over a 2-week period, documented in the past 24 months prior to Screening Visit 1 or during Screening. 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 or other clinically relevant bronchoprovocation testing) documented in the past 24 months prior to Screening Visit 1 or during Screening. 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. General medical history 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. 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 the Baseline Visit without an alternative medical cause. The following age specific requirements apply: 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. Exclusion Criteria: Asthma-related criteria 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. 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. 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. Prohibited medications/procedures 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. General medical history 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. Clinical safety labs 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. Cardiac safety 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. Pregnancy/Lactation 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). 30. Allergy or hypersensitivity to dexpramipexole or any of its components.