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

Asthma Clinical Trial

— EXHALE-2  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05763121
• Other study ID #: AR-DEX-22-01
• Secondary ID: 2022-003004-3320
• Status: Recruiting
• Phase: Phase 3
• Start date: January 30, 2023
• Est. completion date: July 2026

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

This study will assess the efficacy and safety of dexpramipexole as an adjunctive oral therapy in participants with inadequately controlled asthma with an eosinophilic phenotype and a history of asthma exacerbations.

Description:

This is a multicenter, randomized, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of dexpramipexole in adults and adolescents with severe, inadequately controlled asthma with eosinophilic phenotype on medium to high-dose inhaled corticosteroids (ICS )and at least one additional asthma controller medication with or without oral corticosteroids (OCS). Approximately 1400 participants will be randomized globally. Participants will receive dexpramipexole, or placebo, administered orally, over a 52-week treatment period. The study also includes a post-treatment follow-up period of 4 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1395
• Est. completion date: July 2026
• Est. primary completion date: June 2026
• 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

Asthma-related criteria

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

4. 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 Global Initiative for Asthma (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 Screening Visit 1. The ICS may be contained within an ICS/LABA (long-acting ß2 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.

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.

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

6. 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.

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 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) documented in the past past 24 months prior to Screening Visit 1.

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

8. 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

9. Negative urine pregnancy test for women of childbearing potential (WOCBP; after menarche) at the Screening Visit 2 and Baseline Visit.

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 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.

4. 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.

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, 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.

4. For participants aged 12 to 17 years old, AEC of <0.15x10?/L at Screening Visit 1.

Prohibited medications/procedures

5. 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.

6. Treatment with any of the following monoclonal antibody therapies within 120 days prior to Baseline Visit: benralizumab, dupilumab, mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab.

7. Treatment with pramipexole (Mirapex®) within 30 days of Baseline Visit.

8. Treatment with selected drugs known to have a substantial risk of neutropenia in the past 30 days prior to Screening Visit 1.

9. Bronchial thermoplasty procedure in the past 12 months prior to Screening Visit 1 or planned during the coming year.

General medical history

10. Weight <40 kg at Screening Visit 2.

11. Current smoking within the 12 months prior to Screening Visit 1 or a smoking history of >10 pack-years. Smoking includes tobacco, vaping, and/or marijuana use.

12. Known or suspected alcohol or drug abuse

13. Uncontrolled severe hypertension: systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg prior to the Baseline Visit despite antihypertensive therapy.

14. 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.

15. History of human immunodeficiency virus (HIV) infection or chronic infection with hepatitis B or C.

16. 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 (SoC) therapy.

17. Medical or other condition likely to interfere with participant's ability to undergo study procedures, adhere to visit schedule, or comply with study requirements.

18. Known or suspected noncompliance with medication.

19. Unwillingness or inability to follow the procedures outlined in the protocol.

Clinical safety labs

20. Absolute neutrophil count (ANC) <2.000x10?/L at Screening Visit 1 or Screening Visit 2.

21. 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 for age =18 years at screening; using the Bedside Schwartz eGFR formula for age <18).

22. 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

23. History of New York Heart Association class IV heart failure or last known left ventricular ejection fraction <25%.

24. History of major adverse cardiovascular event (MACE) within 3 months prior to the Baseline Visit.

25. History of cardiac arrhythmia within 3 months prior to the Baseline Visit that is not controlled by medication or via ablation.

26. History of long QT syndrome.

27. 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.

28. 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

29. Pregnant women or women breastfeeding

30. Males who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide).

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Argentina	Research Site 20054-005	Córdoba
Argentina	Research Site 20054-010	Mendoza
Argentina	Research Site 20054-013	Rosario
Argentina	Research Site 20054-020	San Miguel De Tucumán
Brazil	Research Site 20055-007	Blumenau
Brazil	Research Site 20055-011	Campo Largo
Brazil	Research Site 20055-004	Porto Alegre	RS
Brazil	Research Site 20055-012	Porto Alegre	RS
Brazil	Research Site 20055-014	Ribeirão Preto	SP
Brazil	Research Site 20055-005	Santo André
Brazil	Research Site 20055-009	Santos	SP
Brazil	Research Site 20055-001	São Bernardo Do Campo	SP
Brazil	Research Site 20055-003	São Paulo
Brazil	Research Site 20055-002	Sorocaba	SP
Bulgaria	Research Site 20359-008	Montana
Bulgaria	Research Site 20359-010	Pernik
Bulgaria	Research Site 20359-005	Ruse
Bulgaria	Research Site 20359-009	Sliven
Bulgaria	Research Site 20359-006	Sofia
Bulgaria	Research Site 20359-003	Stara Zagora
Georgia	Research Site 20995-001	Kutaisi
Georgia	Research Site 20995-002	Tbilisi
Georgia	Research Site 20995-003	Tbilisi
Georgia	Research Site 20995-004	Tbilisi
Korea, Republic of	Research Site 20082-003	Anyang
Korea, Republic of	Research Site 20082-007	Busan
Korea, Republic of	Research Site 20082-009	Daegu
Korea, Republic of	Research Site 20082-006	Jeonju
Korea, Republic of	Research Site 20082-004	Seoul
Korea, Republic of	Research Site 20082-008	Seoul
Korea, Republic of	Research Site 20082-013	Seoul
Korea, Republic of	Research Site 20082-014	Seoul
Korea, Republic of	Research Site 20082-010	Suwon
Poland	Research Site 20048-001	Bedzin
Poland	Research Site 20048-021	Katowice
Poland	Research Site 20048-010	Piaseczno
Poland	Research Site 20048-016	Poznan
Poland	Research Site 20048-014	Skierniewice
Romania	Research Site 20040-008	Bragadiru
Romania	Research Site 200040-004	Brasov	Brasov
Romania	Research Site 20040-002	Brasov
Romania	Research Site 20040-004	Brasov
Romania	Research Site 200040-006	Cluj-Napoca	Cluj
Serbia	Research Site 20381-005	Belgrad
Serbia	Research Site 20381-007	Belgrad
Serbia	Research Site 20381-002	Belgrade
Serbia	Research Site 20381-003	Belgrade
Serbia	Research Site 20381-001	Kragujevac
Serbia	Research Site 20381-004	Niš
Serbia	Research Site 20381-008	Sremska Kamenica
Serbia	Research Site 20381-003	Valjevo
United Kingdom	Research Site 20044-010	Altrincham
United Kingdom	Research Site 20044-018	Bellshill
United Kingdom	Research Site 20044-021	Birmingham
United Kingdom	Research Site 20044-017	Chorley
United Kingdom	Research Site 20044-022	Enfield Town
United Kingdom	Research Site 20044-019	Liverpool
United Kingdom	Research Site 20044-001	Manchester	Greater Manchester
United Kingdom	Research Site 20044-004	Manchester
United Kingdom	Research Site 20044-005	Manchester
United Kingdom	Research Site 20044-009	Manchester
United Kingdom	Research Site 20044-012	Manchester
United Kingdom	Research Site 20044-013	Manchester	Greater Manchester
United Kingdom	Research Site 20044-020	Manchester
United Kingdom	Research Site 20044-030	Manchester
United Kingdom	Research Site 20044-031	Manchester
United Kingdom	Research Site 20044-032	Manchester
United Kingdom	Research Site 20044-033	Manchester	Greater Manchester
United Kingdom	Research Site 20044-046	Manchester	Greater Manchester
United Kingdom	Research Site 20044-024	Preston
United Kingdom	Research Site 20044-026	Rochdale
United Kingdom	Research Site 20044-008	Salford	Greater Manchester
United Kingdom	Research Site 20044-029	Stockport
United Kingdom	Research Site 20044-034	Stockport
United States	Research Site 20001-068	Amarillo	Texas
United States	Research Site 20001-075	Augusta	Georgia
United States	Research Site 20001-048	Aventura	Florida
United States	Research Site 20001-090	Berwyn	Illinois
United States	Research Site 20001-005	Brandon	Florida
United States	Research Site 20001-051	Brandon	Florida
United States	Research Site 20001-340	Burke	Virginia
United States	Research Site 20001-034	Cincinnati	Ohio
United States	Research Site 20001-032	Columbia	South Carolina
United States	Research Site 20001-018	Columbus	Georgia
United States	Research Site 20001-029	Coral Gables	Florida
United States	Research Site 20001-023	Dallas	Texas
United States	Research Site 20001-028	Dallas	Texas
United States	Research Site 20001-017	Dayton	Ohio
United States	Research Site 20001-050	E. Amherst	New York
United States	Research Site 20001-038	Edmond	Oklahoma
United States	Research Site 20001-036	Elwood	Indiana
United States	Research Site 20001-044	Evansville	Indiana
United States	Research Site 20001-006	Flint	Michigan
United States	Research Site 20001-039	Gastonia	North Carolina
United States	Research Site 20001-014	Greenacres City	Florida
United States	Research Site 20001-025	Greenville	South Carolina
United States	Research Site 20001-054	Hialeah	Florida
United States	Research Site 20001-067	Hialeah	Florida
United States	Research Site 20001-020	Homestead	Florida
United States	Research Site 20001-064	Houston	Texas
United States	Research Site 20001-085	Houston	Texas
United States	Research Site 20001-021	Iowa City	Iowa
United States	Research Site 20001-002	Kissimmee	Florida
United States	Research Site 20001-015	Kissimmee	Florida
United States	Research Site 20001-086	Loxahatchee Groves	Florida
United States	Research Site 20001-001	Miami	Florida
United States	Research Site 20001-024	Miami	Florida
United States	Research Site 20001-026	Miami	Florida
United States	Research Site 20001-059	Miami	Florida
United States	Research Site 20001-065	Miami	Florida
United States	Research Site 20001-066	Miami	Florida
United States	Research Site 20001-043	Newport Beach	California
United States	Research Site 20001-062	Newport Beach	California
United States	Research Site 20001-079	Oklahoma City	Oklahoma
United States	Research Site 20001-019	Owensboro	Kentucky
United States	Research Site 20001-135	River Forest	Illinois
United States	Research Site 20001-074	Saint Charles	Missouri
United States	Research Site 20001-046	Saint Louis	Missouri
United States	Research Site 20001-069	Saint Petersburg	Florida
United States	Research Site 20001-073	Spartanburg	South Carolina
United States	Research Site 20001-004	Tampa	Florida
United States	Research Site 20001-072	The Woodlands	Texas
United States	Research Site 20001-063	Toledo	Ohio
United States	Research Site 20001-003	West Covina	California
United States	Research Site 20001-055	White Marsh	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Areteia Therapeutics

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Georgia,  Korea, Republic of,  Poland,  Romania,  Serbia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized rate of severe asthma exacerbations over 52 weeks.	A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for >=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids; or death due to asthma.	Day 1 (baseline, pre-dose) through Week 52
Secondary	Absolute Change in pre-bronchodilator forced expiratory volume (Pre-BD FEV)1 from Baseline	The absolute change from baseline in pre-bronchodilator forced expiratory volume, averaged across visits at Weeks 36, 44, and 52.	Day 1 (baseline, pre-dose), Weeks 36, 44, 52
Secondary	Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6)	Asthma Control Questionnaire-6 (ACQ-6), change from baseline, averaged across visits at Weeks 36, 44, and 52.	Day 1 (baseline, pre-dose), Weeks 36, 44, 52
Secondary	Change in Standardized version of the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ+12) from baseline to Week 52.		Day 1 (baseline, pre-dose) through Week 52
Secondary	Annualized rate of severe exacerbations requiring an emergency department visit or hospitalization over 52 weeks.		Day 1 (baseline, pre-dose) through Week 52
Secondary	Annualized Rate of severe exacerbations from Week 4 to Week 52		Week 4 through Week 52
Secondary	Average change in absolute eosinophil count (AEC)		Day 1 (baseline, pre-dose) Weeks 36, 44, 52
Secondary	Average change from baseline in forced vital capacity (FVC)		Day 1 (baseline, pre-dose), Weeks 36, 44, 52
Secondary	Change from baseline in forced vital capacity (FVC)		Day 1 (baseline, pre-dose), Weeks 4, 12, 20,28 36, 44, 52
Secondary	Change from baseline in Post-bronchodilator FEV1		Day 1 (baseline, pre-dose) through Week 52
Secondary	Change from baseline in peak expiratory flow (PEF)		Day 1 (baseline, pre-dose) through Week 52
Secondary	Time to first severe asthma exacerbation		Up to Week 52
Secondary	Change from baseline in total asthma symptom score		Day 1 (baseline, pre-dose) through Week 52
Secondary	Change from baseline in the EuroQol five-dimensional questionnaire (EQ-5D-5L)		Day 1 (baseline, pre-dose) through Week 52