Asthma MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Dupilumab
Product Code: SAR231893
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Dupilumab
Current Sponsor code: SAR231893
Other descriptive name:
Sponsors
Sanofi-Aventis Groupe
Eligibility
Sex/Gender
All
Inclusion criteria
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 298 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 -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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of dupilumab on lung inflammation 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. To evaluate safety of dupilumab ;Primary end point(s): 1/ Proportion of participants achieving FeNO <25 parts per billion (ppb) at Week 24. 2/ Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at total lung capacity (TLC).;Timepoint(s) of evaluation of this end point: 1/ Week 24 2/ Baseline to Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1/ Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at functional residual capacity (FRC). 2/ Percent change from baseline to Week 24 in trimmed distal airway resistance corrected for lung volume ([s]iRaw) at TLC. 3/ Percent change from baseline to Week 24 in trimmed distal airway resistance corrected for lung volume ([s]iRaw) at FRC 4/ Change from baseline to Week 24 in global lung lobar volumes (iVlobes) at TLC 5/ Change from baseline to Week 24 in HRCT-based internal airflow distribution (IAD) for each lung zone 6/ Change from baseline to Week 24 in image-based ventilation/perfusion (iV/Q) at TLC for each lung zone 7/ Change from baseline to Week 24 in global lung mucus scoring (UCSF mucus scoring) 8/ Change from baseline to Week 24 in FeNO 9/ Change from baseline to Week 24 in pre-bronchodilator FEV1 10/ Change from baseline to Week 24 in post-bronchodilator FEV1 11/ Change from baseline to Week 24 in Asthma Control Questionnaire 7 (ACQ-7) 12/ Incidence of treatment emergent adverse events (TEAE) and serious adverse events (SAE) including clinically significant changes in vital signs and laboratory abnormalities 13/ Incidence of adverse events of special interest (AESI );Timepoint(s) of evaluation of this end point: 1-11/ Baseline to Week 24 12-13/ Baseline through Week 36 | — |
Countries
Bulgaria, Denmark, France, Italy, Portugal, Romania, Saudi Arabia, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Study Unit
Sanofi AB
Outcome results
None listed