Active, not recruiting
Phase 4
Study Assessing the Long-term Effect of Dupilumab on Prevention of Lung Function Decline in Adult Patients With Uncontrolled Moderate to Severe Asthma
Condition(s) studied
Asthma
Investigational drug(s) / intervention(s)
DupilumabPlacebo
Dupilumab: solution for injection subcutaneous
Placebo: solution for injection subcutaneous
Study summary
This is an interventional, randomized, parallel group, treatment, Phase 3b/4, double blind, 2-arm study to assess the effect of dupilumab compared to standard of care therapy on preventing or slowing the rate of lung function decline in adult patients with uncontrolled moderate to severe asthma.
The estimated duration is 4±1 weeks of screening and run-in period, followed by a 3-year double blinded treatment period. There will be a post-treatment follow-up (FU) period up to 12 weeks.
Eligibility
Inclusion Criteria:
* Participant must be at least 18 (or the legal age of consent in the jurisdiction in which the study is taking place) years of age inclusive, at the time of signing the informed consent.
* Patients with a physician diagnosis of asthma (according to Global Initiative for Asthma (GINA) 2021) for ≥12 months
* Treatment with medium to high dose inhaled corticosteroids (ICS) in combination with a second controller (eg, long-acting beta-2 adrenergic receptor agonists (LABA), leukotriene receptor antagonists (LTRA) with a stable dose ≥1 month prior to Visit 1. Patients requiring a third controller for their asthma will be considered eligible for this study, and it should also be on stable dose ≥1 month prior to Visit 1. Patients requiring an additional controller as a fourth controller (Montelukast) for another type 2 comorbid condition such as allergic rhinitis will be considered eligible for this study, and should be on a stable dose for ≥1 month prior to Visit 1.
* Pre-bronchodilator forced expiratory volume (FEV1) ≤ 80% of predicted normal for adults at Visits 1 and 2, prior to randomization
* Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at Visits 1 and 2, prior to randomization.
* Variable airflow obstruction as documented by one or more of the following (at least 1 needs to be met):
i) Positive reversibility test: ≥12% and 200 mL improvement in FEV1 after SABA administration prior to randomization, or documented in the 24 months prior to Visit 1. OR, ii) Positive bronchial challenge test: fall in FEV1 of ≥20% with standard doses of methacholine, or ≥15% with standardized hyperventilation, hypertonic saline or mannitol challenge prior to randomization or documented in the 24 months prior to Visit 1 OR, iii) Average daily diurnal Peak flow variability of \>10% over a 2-week period, documented in the past 24 months prior to Screening Visit 1. OR, iv) Airflow variability in clinic FEV1 \>12% and 200 mL between visits outside of respiratory infections, documented in the past 24 months prior to Screening Visit 1. OR v) FEV1 increases by more than 12% and 200mL from baseline after 4 weeks of anti-inflammatory treatment.
* Reversibility test: Three attempts may be made during the Screening Period until the Baseline visit to meet the qualifying criteria for reversibility. This is only required if reversibility or other evidence of expiratory airflow limitation eligibility criteria was not performed within 24 months prior to Visit 1.
* FeNO ≥35 ppb at Visit 2, prior to randomization.
* History of ≥1 severe exacerbation(s) in the previous year before Visit1 defined as a deterioration of asthma requiring:
i) Use of systemic corticosteroids for ≥3 days; or ii) Hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
* History or clinical evidence of chronic obstructive pulmonary disease (COPD) including Asthma-COPD Overlap Syndrome (ACOS) or any other significant lung disease (eg, emphysema, lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome).
* Severe asthma exacerbation requiring treatment with systemic corticosteroid (SCS) in the past month before visit 1 or during the screening period.
* Current acute bronchospasm or status asthmaticus.
* Diagnosed pulmonary (other than asthma) or systemic disease associated with elevated peripheral eosinophil counts.
* Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the participant's participation in the study. Examples include, but are not limited to, participants with short life expectancy, uncontrolled diabetes, cardiovascular conditions, severe renal conditions (eg, participants on dialysis), or other severe endocrinological, gastrointestinal, metabolic, pulmonary, psychiatric, or lymphatic diseases. The specific justification for participants excluded under this criterion will be noted in the study documents (chart notes, case report forms \[CRFs\], etc).
* Patients with active tuberculosis (TB) or non-tuberculous mycobacterial infection, or a history of incompletely treated TB will be excluded from the study unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent, in the medical judgment of the Investigator and/or infectious disease specialist. Tuberculosis testing will be performed on a country by country basis, according to local guidelines if required by regulatory authorities or ethics boards, or if TB is suspected by the investigator
* Known or suspected immunodeficiency, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune-compromised status, as judged by the Investigator.
* Active malignancy or history of malignancy within 5 years before Visit 1 (screening visit), except completely treated in situ carcinoma of the cervix and completely treated and resolved non metastatic squamous or basal cell carcinoma of the skin.
* Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antifungals or receiving only symptomatic treatment (e.g. influenza or COVID-19) within 2 weeks before the screening visit (Visit 1) or during the screening period.
* History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Visit 1 (screening visit).
* Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drugs within 2 weeks before Visit 1 (screening visit) or during the screening and run-in period
* Current smoker (cigarette or e-cigarette) or cessation of smoking within 6 months prior to Visit 1.
* Previous smoker with a smoking history \>10 pack-years.
* History of systemic hypersensitivity or anaphylaxis to dupilumab or any other biologic therapy, including any excipient.
* Any biologic therapy (including experimental treatments and dupilumab) or any other biologic therapy/immunosuppressant/immunomodulators within 4 weeks prior to V1 or 5 half-lives, whichever is longer.
* Treatment with a live (attenuated) vaccine within 4 weeks before Visit 1 (screening visit) or during the screening period.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Primary outcome measure(s)
- Rate of change from week 8 to week 52 on post-BD FEV1 slope in FeNO population — Week 8 to Week 52
Rate of change from week 8 to week 52 on post-bronchodilator (BD) forced expiratory volume in one second (FEV1) slope in FeNO population.
Trial sites (249)
| Facility | City | Region | Status |
| Cullman Research Center- Site Number : 8400001 |
Cullman |
Alabama |
|
| Shoals Primary Care - Sheffield- Site Number : 8400015 |
Sheffield |
Alabama |
|
| Chandler Clinical Research Trials- Site Number : 8400147 |
Chandler |
Arizona |
|
| Pulmonary Associates - Deer Valley Office- Site Number : 8400155 |
Phoenix |
Arizona |
|
| Medical Advancement Center of Arizona (MACOA)- Site Number : 8400130 |
Phoenix |
Arizona |
|
| Del Sol Research Management - Tucson- Site Number : 8400017 |
Tucson |
Arizona |
|
| Kern Allergy and Medical Research- Site Number : 8400037 |
Bakersfield |
California |
|
| Vitality Clinical Research- Site Number : 8400142 |
Beverly Hills |
California |
|
| Ascada Research - Fullerton- Site Number : 8400076 |
Fullerton |
California |
|
| Allergy and Asthma Specialists Medical Group- Site Number : 8400162 |
Huntington Beach |
California |
|
| Newport Native MD- Site Number : 8400054 |
Newport Beach |
California |
|
| Prospective Research Innovations- Site Number : 8400131 |
Rancho Cucamonga |
California |
|
| Mercy Medical Group - Midtown- Site Number : 8400164 |
Sacramento |
California |
|
| Integrated Research of Inland- Site Number : 8400156 |
Upland |
California |
|
| Allianz Research Institute- Site Number : 8400018 |
Westminster |
California |
|
| Woodland Clinic - Woodland- Site Number : 8400171 |
Woodland |
California |
|
| Central Florida Pulmonary Group - Altamonte Springs- Site Number : 8400035 |
Altamonte Springs |
Florida |
|
| Florida Center for Allergy & Asthma Research- Site Number : 8400032 |
Aventura |
Florida |
|
| Beautiful Minds Clinical Research Center- Site Number : 8400141 |
Cutler Bay |
Florida |
|
| Omega Research Consultants - Debary - North Charles Richard Beall Boulevard- Site Number : 8400023 |
DeBary |
Florida |
|
| Florida Lung, Asthma and Sleep Specialists (FLASS) - Polynesian- Site Number : 8400098 |
Kissimmee |
Florida |
|
| Ivetmar Medical Group- Site Number : 8400063 |
Miami |
Florida |
|
| My Preferred Research- Site Number : 8400073 |
Miami |
Florida |
|
| Research Institute of South Florida- Site Number : 8400079 |
Miami |
Florida |
|
| Floridian Clinical Research - Miami Lakes- Site Number : 8400091 |
Miami Lakes |
Florida |
|
| Heuer M.D. Research- Site Number : 8400024 |
Orlando |
Florida |
|
| JSV Clinical Research- Site Number : 8400150 |
Tampa |
Florida |
|
| Appalachian Clinical Research- Site Number : 8400129 |
Adairsville |
Georgia |
|
| Alpha Clinical Research Group - Dunwoody- Site Number : 8400116 |
Dunwoody |
Georgia |
|
| Aeroallergy Research Laboratory- Site Number : 8400114 |
Savannah |
Georgia |
|
| Rush University Medical Center- Site Number : 8400146 |
Chicago |
Illinois |
|
| NorthShore University Health System - Endeavor Health Medical Group - Skokie - Woods Drive- Site Number : 8400138 |
Skokie |
Illinois |
|
| Family Allergy & Asthma - Louisville - Goss Avenue- Site Number : 8400160 |
Louisville |
Kentucky |
|
| Allergy and Asthma Specialist- Site Number : 8400007 |
Owensboro |
Kentucky |
|
| Avant Research Associates - Crowley- Site Number : 8400117 |
Crowley |
Louisiana |
|
| Investigational Site Number : 3560016 |
Houma |
Louisiana |
|
| Tandem Clinical Research - Metairie- Site Number : 8400163 |
Metairie |
Louisiana |
|
| Javara Privia Mid-Atlantic - Annapolis- Site Number : 8400087 |
Annapolis |
Maryland |
|
| Urgent Care Clinical Trials and KUR Research- Site Number : 8400169 |
Columbia |
Maryland |
|
| Chesapeake Clinical Research - White Marsh- Site Number : 8400119 |
White Marsh |
Maryland |
|
+ 209 more sites — see the full list on the official registry below.