The effect of dupilumab on lung inflammation and related changes inairway volumes detectable by functional respiratory imaging in patientswith moderate-severe asthma
- Conditions
- AsthmaMedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2019-004647-74-DK
- Lead Sponsor
- Sanofi-Aventis Groupe
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 298
-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 298
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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
-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)
-Active tuberculosis, latent untreated tuberculosis or a history of
incompletely treated tuberculosis or non-tuberculous mycobacterial
infection unless it is well documented by a specialist that the participant
has been adequately treated and the treatment with a biologic agent can
be initiated, in the medical judgment of the Investigator and/or
infectious disease specialist. Tuberculosis testing would only be
performed on a country by country basis according to the routine clinical
practice and the local guidelines, if required by regulatory authorities or
ethics committees
-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 4 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:
-- Participants for whom administration of live (attenuated) vaccine can
be safely postponed would be eligible to enroll into the study.
-- Participants 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 a
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 inflammation and related<br>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/ Proportion of participants achieving FeNO <25 parts per billion (ppb)<br>at Week 24.<br>2/ Percent change from baseline to Week 24 in untrimmed distal airway<br>volumes corrected for lung volume ([s]iVaw) at total lung capacity<br>(TLC).;Timepoint(s) of evaluation of this end point: 1/ Week 24<br>2/ Baseline to Week 24
- Secondary Outcome Measures
Name Time Method