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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
First received
Last updated
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
Health authority
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).

Study Design


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
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