Study Assessing the Long-term Effect of Dupilumab on Prevention of Lung Function Decline in Adult Patients With Uncontrolled Moderate to Severe Asthma
- Registration Number
- NCT05097287
- Lead Sponsor
- Sanofi
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1324
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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.
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Patients with a physician diagnosis of asthma (according to Global Initiative for Asthma (GINA) 2021) for ≥12 months
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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.
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Pre-bronchodilator forced expiratory volume (FEV1) ≤ 80% of predicted normal for adults at Visits 1 and 2, prior to randomization
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Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at Visits 1 and 2, prior to randomization.
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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.
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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.
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FeNO ≥35 ppb at Visit 2, prior to randomization.
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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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dupilumab Dupilumab Dupilumab administered every 2 weeks (Q2W) after an initial loading dose (2 injections) on Day 1 Placebo Placebo Matching placebo administered Q2W after an initial loading dose (2 injections) on Day 1
- Primary Outcome Measures
Name Time Method 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.
- Secondary Outcome Measures
Name Time Method Rate of change from week 8 to week 52 on post-BD FEV1 slope in the Total population Week 8 to Week 52 Rate of change from week 8 to week 52 on post-BD FEV1 slope in the Total population.
Rate of change from week 8 to week 156 on post-BD FEV1 slope in FeNO and Total populations Week 8 to Week 156 Rate of change from week 8 to week 156 on post-BD FEV1 slope in FeNO and Total populations.
Change from baseline to week 52 in Asthma Control Questionnaire 7 items (ACQ-7) in FeNO and Total populations Baseline to Week 52 ACQ-7 was designed to measure both the adequacy of asthma control and change in asthma control. A global score ranges between 0 (totally controlled) and 6 (severely uncontrolled). Higher score indicates lower asthma control.
Change from baseline to week 52 in pre-BD FEV1 % predicted in FeNO and Total populations Baseline to Week 52 Change from baseline to week 52 in pre-BD FEV1 % predicted in FeNO and Total populations.
Rate of change from week 8 to week 104 on post-BD FEV1 slope in Total Population Week 8 to Week 104 Rate of change from week 8 to week 104 on post-BD FEV1 slope in Total Population.
Change from baseline to week 104 in pre-BD FEV1 in FeNO and Total populations Baseline to Week 104 Change from baseline to week 104 in pre-BD FEV1 in FeNO and Total populations.
Change from baseline to week 104 in post-BD FEV1 in FeNO and Total populations Baseline to Week 104 Change from baseline to week 104 in post-BD FEV1 in FeNO and Total populations.
Annualized severe exacerbation rate during the 104-week period in FeNO and Total populations Baseline to Week 104 Exacerbation 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.
Change from baseline to week 104 in FeNO levels in FeNO and Total populations Baseline to Week 104 Change from baseline to week 104 in FeNO levels in FeNO and Total populations.
Change from baseline to week 104 in ACQ-7 in FeNO and Total populations Baseline to Week 104 ACQ-7 was designed to measure both the adequacy of asthma control and change in asthma control. A global score ranges between 0 (totally controlled) and 6 (severely uncontrolled). Higher score indicates lower asthma control.
Change from baseline to week 104 in pre-BD FEV1 % predicted in FeNO and Total populations Baseline to Week 104 Change from baseline to week 104 in pre-BD FEV1 % predicted in FeNO and Total populations.
Change from baseline to week 104 FVC in FeNO and Total populations Baseline to Week 104 Change from baseline to week 104 FVC in FeNO and Total populations.
Change from baseline to week 52 in Asthma Quality Of Life Questionnaire with Standardized Activities (AQLQ(S)) in FeNO and Total populations Baseline to Week 52 The AQLQ (S) was designed as a self-administered patient reported outcome to measure the functional impairments that are most troublesome to patients as a result of their asthma. A global score is calculated ranging from 1 to 7. Higher scores indicate better quality of life.
Change from baseline to week 104 in AQLQ(S) in FeNO and Total populations Baseline to Week 104 The AQLQ (S) was designed as a self-administered patient reported outcome to measure the functional impairments that are most troublesome to patients as a result of their asthma. A global score is calculated ranging from 1 to 7. Higher scores indicate better quality of life.
Rate of change from week 8 to week 104 on post-BD FEV1 slope in the FeNO population Week 8 to Week 104 Rate of change from week 8 to week 104 on post-BD FEV1 slope in the FeNO population.
Change from baseline to week 52 in pre-BD FEV1 in FeNO and Total populations Baseline to Week 52 Change from baseline to week 52 in pre-BD FEV1 in FeNO and Total populations.
Change from baseline to week 52 in Forced Vital Capacity (FVC) in FeNO and Total populations Baseline to Week 52 Change from baseline to week 52 in FVC in FeNO and Total populations.
Change from baseline to week 52 in post-BD FEV1 in FeNO and Total populations Baseline to Week 52 Change from baseline to week 52 in post-BD FEV1 in FeNO and Total populations.
Annualized severe exacerbation rate during the 52-week period in FeNO and Total populations Baseline to Week 52 Exacerbation 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.
Change from baseline to week 52 in fractional exhaled nitric oxide (FeNO) levels in FeNO and Total populations Baseline to Week 52 Change from baseline to week 52 in FeNO levels in FeNO and Total populations.
Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) Baseline to Week 168 Incidence of TEAEs and SAEs.
Incidence of adverse events of special interest (AESIs) Baseline to Week 168 Incidence of AESIs.
Trial Locations
- Locations (248)
Cullman Research Center- Site Number : 8400001
🇺🇸Cullman, Alabama, United States
Shoals Primary Care - Sheffield- Site Number : 8400015
🇺🇸Sheffield, Alabama, United States
Chandler Clinical Research Trials- Site Number : 8400147
🇺🇸Chandler, Arizona, United States
Pulmonary Associates - Deer Valley Office- Site Number : 8400155
🇺🇸Phoenix, Arizona, United States
Medical Advancement Center of Arizona (MACOA)- Site Number : 8400130
🇺🇸Tempe, Arizona, United States
Del Sol Research Management - Tucson- Site Number : 8400017
🇺🇸Tucson, Arizona, United States
Kern Allergy and Medical Research- Site Number : 8400037
🇺🇸Bakersfield, California, United States
Vitality Clinical Research- Site Number : 8400142
🇺🇸Beverly Hills, California, United States
Ascada Research - Fullerton- Site Number : 8400076
🇺🇸Fullerton, California, United States
Allergy and Asthma Specialists Medical Group- Site Number : 8400162
🇺🇸Huntington Beach, California, United States
Scroll for more (238 remaining)Cullman Research Center- Site Number : 8400001🇺🇸Cullman, Alabama, United States