The effect of dupilumab on lung function and related changes in airway volumes detectable by functional respiratory imaging in patients with moderate-severe asthma

Phase 1

Conditions: Asthma
MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2019-004647-74-PT

Lead Sponsor: Sanofi-Aventis Groupe

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 109

Inclusion Criteria

-18 to 70 years of age inclusive with the diagnosis of asthma based on Global Strategy for Asthma Management and Prevention (GINA) 2019 at the time of signing the informed consent
-History of =1 exacerbation (s) in the previous year
-Uncontrolled moderate to severe asthma (ACQ-5 =1.5) at V1 and V2, prior to randomization
-Pre-bronchodilator FEV1 =80% of predicted normal at V1 and V2, prior to randomization
-Exhibit bronchodilator reversibility (=12% and 200 mL improvement in FEV1 post SABA administration) during screening, prior to randomization
-Blood eosinophil =300 cells /µL and FeNO =25 ppb during screening, prior to randomization
NOTES:
-- Historical values of blood eosinophil count meeting the eligibility criterion measured
within 6 months prior to SV1 in the absence of OCS treatment are allowed.
-- FeNO value to be checked for eligibility at V2 as well.
-Existing treatment with medium to high dose ICS in combination with a second controller (e.g. LABA, LTRA) ± a third controller. The dose regimen should be stable =1 month prior V1 and during screening.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 340
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Current smoker (cigarette or e-cigarette) or cessation of smoking within 1 year prior randomization
-Previous smoker with a smoking history >10 pack-years
-Known hypersensitivity to dupilumab or any of its excipients
-A subject who experiences an asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids) during screening
-Asthma exacerbation during the screening, prior to randomization
-Current acute bronchospasm or status asthmaticus
-Diagnosed pulmonary (other than asthma) or systemic disease associated with elevated peripheral eosinophil counts
-History or clinical evidence of chronic obstructive pulmonary disease (COPD) including Asthma-COPD Overlap Syndrome (ACOS) or any other significant lung disease (eg, lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome, etc)
-History of or current evidence of clinically significant disease in any non-respiratory system (e.g. cardiovascular, nervous system, gastrointestinal, endocrinological, rheumatological, dermatological), which, in the judgment of the Investigator, could interfere with the study or require treatment that might interfere with the study
-Current evidence of clinically significant oncological disease, which in the opinion of the investigator may interfere with the objectives of the study or put the subject at undue risk
-Participants with any of the following results at Visit (V) 1:
-Positive (or indeterminate) hepatitis B surface antigen (HBs Ag) or
-Positive Hepatitis B IgM core antibody (IgM HBc Ab) or
-Positive total hepatitis B core antibody (total HBc Ab) confirmed by positive HBV DNA or
-Positive hepatitis C antibody (HCV Ab) confirmed by positive HCV RNA
-History of human immunodeficiency virus (HIV) infection or positive HIV serology at V 1
-Any biologic therapy (including experimental treatments and dupilumab) or any other biologic therapy/immunosuppressant within 3 months prior to V1
-Treatment with live (attenuated) vaccine within 12 weeks before V1
For participants who have vaccination with live, attenuated vaccines planned during the course of the study (based on national vaccination schedule/local guidelines), it will be determined, after consultation with a physician, whether the administration of vaccine can be postponed until after the end of the study, or preponed to before the start of the study without compromising the health of the participant:
-- Patients for whom administration of live (attenuated) vaccine can be safely postponed would be eligible to enroll into the study.
-- Patients who have their vaccination preponed can enroll in the study only after a gap of 4 weeks following administration of the vaccine.
-Treatment with oral corticosteroids (OCS) within 2 weeks prior to V1
-Enrolled in other ongoing studies regardless of the investigational product
-Treatment with an investigational drug within 1 month or within 5 half-lives (if known), whichever is longer, prior to V1
-Suspected or high risk of parasitic infection (helminthic infection), unless clinical and (if necessary) laboratory assessments have ruled out active infection prior to randomization
-Females who are lactating, breastfeeding, or who are pregnant
-Individuals accommodated in an institution because of regulatory or legal order; prisoners or subjects who are legally institutionalized

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the effect of dupilumab on lung function and related changes in airway volumes detectable by functional respiratory imaging;Secondary Objective: To evaluate the effect of dupilumab at Week 24 on bronchodynamics, hyperinflation, airway resistance, airway wall thickness, ventilation defects and mucus plugging derived from high-resolution computed tomography (HRCT) scans, patient-reported outcomes, FeNO and spirometry.<br>To evaluate safety of dupilumab <br>;Primary end point(s): 1/ Change from baseline to Week 24 in pre-bronchodilator FEV1<br>2/ Percent change from baseline to Week 24 in regional airway volumes corrected for lung volume ([s]iVaw) at total lung capacity (TLC);Timepoint(s) of evaluation of this end point: Baseline to Week 24

Secondary Outcome Measures

Name	Time	Method

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