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

Asthma; Eosinophilic Clinical Trial

— EXHALE-4  

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Dexpramipexole Administered Orally for 24 Weeks in Participants With Eosinophilic Asthma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05748600
• Other study ID #: AR-DEX-22-03
• Secondary ID: 2022-003005-30
• Status: Recruiting
• Phase: Phase 3
• Start date: January 30, 2023
• Est. completion date: April 2025

Study information

• Verified date: February 2024
• Source: Areteia Therapeutics
• Contact: EXHALE Recruiting
• Phone: 888-584-9281
• Email: clinicaltrials[@]areteiatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate dexpramipexole as an add-on oral therapy in participants with inadequately controlled eosinophilic asthma to evaluate improvements in lung function, asthma control, and quality of life. In addition, the study will further evaluate the safety and tolerability of dexpramipexole in participants with eosinophilic asthma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 550
• Est. completion date: April 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 99 Years

Eligibility

Inclusion Criteria:

1. Signed informed consent form and assent form, as appropriate.

2. Male or female =12 years of age at Screening Visit 1. Sites in Poland will only include participants aged =18 years.

Asthma-related criteria

3. Documented physician diagnosis of asthma for =12 months prior to Screening Visit 1.

4. Participants requiring at a minimum daily low dose inhaled corticosteroids (ICS; =100 µg/day fluticasone propionate dry powder formulation daily or clinically comparable, per GINA 2021), plus one or more additional daily maintenance asthma controller medications, eg, long-acting ß2 agonist (LABA), leukotriene antagonist, theophylline, long-acting muscarinic antagonists, cromolyn/nedocromil. Note: In Poland, this will instead include participants requiring a minimum daily medium dose ICS (=500 µg/day fluticasone propionate dry powder formulation daily or clinically comparable, per GINA 2021). Use of daily ICS must be for at least 12 weeks prior to Screening Visit 1 and the doses of all controller medications must be stable for at least 4 weeks prior to Screening Visit 1.

5. Pre-BD FEV1 =40% and <80% (<90% for participants 12 to 17 years of age) of predicted at Screening Visit 2.

6. 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.

7. ACQ-6 =1.5 at Screening Visit 2.

8. 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).

General medical history

9. Negative urine pregnancy test for women of childbearing potential (WOCBP; after menarche) at the Screening and Baseline visits.

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.

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. least 7 days prior to baseline.

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 prior to the 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, or 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-interleukin-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 study period.

General medical history

9. Weight <40 kg at Screening Visit 2.

10. Current smoking within 12 months prior to Screening Visit 1 or a smoking history of >10 packyears. 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 the Baseline Visit despite antihypertensive 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 the 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 to Screening Visit 1, that has not been treated with or has failed to respond to standard of care 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 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 the 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 resting 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).

For this study, rescreening may only be permitted under specific circumstances and only after contact with a Sponsor Clinical representative.

Related Conditions & MeSH terms

• Asthma
• Asthma Attack
• Asthma; Eosinophilic
• Eosinophilic Asthma
• Pulmonary Eosinophilia

Intervention

Drug:
• Dexpramipexole Dihydrochloride
administration of dexpramipexole tablet
• Placebo
administration of placebo tablet

Locations

Country	Name	City	State
Poland	Research Site 40048-001	Bedzin
Poland	Research Site 40048-006	Gizycko
Poland	Research Site 40048-021	Katowice
Poland	Research Site 40048-008	Kraków
Poland	Research Site 40048-010	Piaseczno
Poland	Research Site 40048-016	Poznan
Poland	Research Site 40048-014	Skierniewice
Poland	Research Site 40048-012	Trzebnica
Romania	Research Site 40040-002	Brasov
Romania	Research Site 40040-004	Brasov	Brasov
Romania	Research Site 40040-006	Cluj-Napoca	Cluj
Romania	Research Site 40040-007	Cluj-Napoca
Romania	Research Site 40040-001	Constanta
Romania	Research Site 40040-003	Timisoara
United Kingdom	Research Site 40044-010	Altrincham
United Kingdom	Research Site 40044-018	Bellshill
United Kingdom	Research Site 40044-021	Birmingham
United Kingdom	Research Site 40044-017	Chorley
United Kingdom	Research Site 40044-022	Enfield Town
United Kingdom	Research Site 40044-019	Liverpool
United Kingdom	Research Site 40044-001	Manchester
United Kingdom	Research Site 40044-004	Manchester
United Kingdom	Research Site 40044-005	Manchester
United Kingdom	Research Site 40044-006	Manchester
United Kingdom	Research Site 40044-009	Manchester
United Kingdom	Research Site 40044-012	Manchester
United Kingdom	Research Site 40044-013	Manchester
United Kingdom	Research Site 40044-013	Manchester
United Kingdom	Research Site 40044-020	Manchester
United Kingdom	Research Site 40044-030	Manchester
United Kingdom	Research Site 40044-031	Manchester
United Kingdom	Research Site 40044-032	Manchester
United Kingdom	Research Site 40044-033	Manchester
United Kingdom	Research Site 40044-036	Manchester
United Kingdom	Research Site 40044-002	Oldham
United Kingdom	Research Site 40044-024	Preston
United Kingdom	Research Site 40044-026	Rochdale
United Kingdom	Research Site 40044-008	Salford
United Kingdom	Research Site 40044-029	Stockport
United Kingdom	Research Site 40044-034	Stockport
United Kingdom	Research Site 40044-063	Wigan
United States	Research Site 40001-334	Allen	Texas
United States	Research Site 40001-068	Amarillo	Texas
United States	Research Site 40001-075	Augusta	Georgia
United States	Research Site 40001-048	Aventura	Florida
United States	Research Site 40001-090	Berwyn	Illinois
United States	Research Site 40001-005	Brandon	Florida
United States	Research Site 40001-051	Brandon	Florida
United States	Research Site 40001-340	Burke	Virginia
United States	Research Site 40001-343	Chicago	Illinois
United States	Research Site 40001-034	Cincinnati	Ohio
United States	Research Site 40001-353	Colorado Springs	Colorado
United States	Research Site 40001-032	Columbia	South Carolina
United States	Research Site 40001-083	Columbia	Missouri
United States	Research Site 40001-018	Columbus	Georgia
United States	Research Site 40001-029	Coral Gables	Florida
United States	Research Site 40001-023	Dallas	Texas
United States	Research Site 40001-028	Dallas	Texas
United States	Research Site 40001-017	Dayton	Ohio
United States	Research Site 40001-050	E. Amherst	New York
United States	Research Site 40001-363	Edison	New Jersey
United States	Research Site US-40001-038	Edmond	Oklahoma
United States	Research Site 40001-036	Elwood	Indiana
United States	Research Site 40001-006	Flint	Michigan
United States	Research Site 40001-350	Gainesville	Florida
United States	Research Site 40001-039	Gastonia	North Carolina
United States	Research Site 40001-027	Grants Pass	Oregon
United States	Research Site 40001-037	Grants Pass	Oregon
United States	Research Site 40001-014	Greenacres City	Florida
United States	Research Site 40001-339	Greenfield	Wisconsin
United States	Research Site 40001-025	Greenville	South Carolina
United States	Research Site 40001-047	Hawthorne	New York
United States	Research Site 40001-054	Hialeah	Florida
United States	Research Site 40001-067	Hialeah	Florida
United States	Research Site 40001-020	Homestead	Florida
United States	Research Site 40001-064	Houston	Texas
United States	Research Site 40001-085	Houston	Texas
United States	Research Site 40001-002	Kissimmee	Florida
United States	Research Site 40001-015	Kissimmee	Florida
United States	Research Site 40001-357	Lancaster	California
United States	Research Site 40001-366	Lilburn	Georgia
United States	Research Site 40001-086	Loxahatchee Groves	Florida
United States	Research Site 40001-318	Maitland	Florida
United States	Research Site 40001-313	Marrero	Louisiana
United States	Research Site 40001-001	Miami	Florida
United States	Research Site 40001-024	Miami	Florida
United States	Research Site 40001-026	Miami	Florida
United States	Research Site 40001-059	Miami	Florida
United States	Research Site 40001-065	Miami	Florida
United States	Research Site 40001-066	Miami	Florida
United States	Research Site 40001-338	Miami Beach	Florida
United States	Research Site 40001-362	Mission Viejo	California
United States	Research Site 40001-043	Newport Beach	California
United States	Research Site 40001-062	Newport Beach	California
United States	Research Site 40001-348	Ocala	Florida
United States	Research Site 40001-079	Oklahoma City	Oklahoma
United States	Research Site 40001-019	Owensboro	Kentucky
United States	Research Site 40001-333	Pleasant View	Utah
United States	Research Site 40001-337	Portland	Oregon
United States	Research Site 40001-304	Red Oak	Texas
United States	Research Site 40001-135	River Forest	Illinois
United States	Research Site 40001-074	Saint Charles	Missouri
United States	Research Site 40001-046	Saint Louis	Missouri
United States	Research Site 40001-069	Saint Petersburg	Florida
United States	Research Site 40001-377	San Antonio	Texas
United States	Research Site 40001-088	San Jose	California
United States	Research Site 40001-073	Spartanburg	South Carolina
United States	Research Site 40001-335	Sugar Land	Texas
United States	Research Site 40001-322	Surprise	Arizona
United States	Research Site 40001-370	Tallahassee	Florida
United States	Research Site 40001-004	Tampa	Florida
United States	Research Site 40001-063	Toledo	Ohio
United States	Research Site 40001-359	Upland	California
United States	Research Site 40001-319	Viera	Florida
United States	Research Site 40001-372	Warren	Michigan
United States	Research Site 40001-003	West Covina	California
United States	Research Site 40001-055	White Marsh	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Areteia Therapeutics

Countries where clinical trial is conducted

United States,  Poland,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in pre-BD FEV1 from baseline	Pre-bronchodilator forced expiratory volume (pre-BD) FEV1, absolute change from baseline, averaged over Weeks 20 and 24.	Day 1 (baseline, pre-dose), Weeks 20, 24
Secondary	Change from baseline in Asthma Control Questionnaire-6 (ACQ-6)	Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) averaged over visits at Weeks 20 and 24.	Day 1 (baseline, pre-dose), Weeks 20, 24
Secondary	Change in Standardized version of the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ+12) from baseline to Week 24.		Day 1 (baseline, pre-dose) through Week 24
Secondary	Change from baseline absolute eosinophil count (AEC) averaged across Weeks 20 and 24.		Day 1 (baseline, pre-dose) through Week 24
Secondary	Change from baseline forced vital capacity (FVC) averaged over Weeks 20 and 24.		Day 1 (baseline, pre-dose), Weeks 20, 24
Secondary	Change from baseline forced vital capacity (FVC) at Weeks 4, 8, 12, 16, 20, and 24.		Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16, 20, and 24
Secondary	Change from baseline post-bronchodilator (post-BD) forced expiratory volume (FEV1) at Week 24.		Day 1 (baseline, pre-dose) through Week 24
Secondary	The EuroQol 5-dimensional questionnaire (EQ-5D-5L) change from baseline to Week 24		Day 1 (baseline, pre-dose) through Week 24