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

Overview

About this study

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

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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 ≥0.30x10?/L at Screening Visit 1. If the initial value is between
0.250x10?/L to 0.299x10?/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 ?g/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 ?2 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 FEV? ≥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 FEV?, 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 FEV? ≥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 FEV?
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.

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 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.

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 <2.000x10?/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).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 12/21/23. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Thanai Pongdee, M.D.

Contact us for the latest status

Contact information:

Robert McBane

(507) 293-1433

McBane.Robert1@mayo.edu

More information

Publications

Publications are currently not available
.
CLS-20566563

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