The Effect of Dupilumab on Lung Function and Related Changes in Airway Volumes Detectable by Functional Respiratory Imaging in Patients With Moderate-severe Asthma

Overview

Primary Objective:

o 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.

- To evaluate safety of dupilumab

Full Title of Study: “Randomized, Double Blind, Placebo Controlled Study to Evaluate the Effect of Dupilumab on Airway Inflammation Through Assessments of Lung Function, Mucus Plugging and Other Lung Imaging Parameters in Patients With Asthma”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: February 2022

Detailed Description

The study duration for each participant will be a total of minimum 29 weeks and up to 41 weeks. This includes 4 weeks +/-1 week screening period, 24 weeks of treatment period and a follow-up period up to 12 weeks or until the patients switch to commercialized dupilumab (or other biologic products), whatever comes first.

Interventions

  • Drug: Dupilumab SAR231893
    • Pharmaceutical form:solution for injection Route of administration: subcutaneous
  • Drug: Placebo
    • Pharmaceutical form:solution for injection Route of administration: subcutaneous

Arms, Groups and Cohorts

  • Experimental: Dupilumab
    • 2 x loading dose on Day 1, followed by 1 x maintenance dose every 2 weeks (Q2W) during 24 weeks
  • Placebo Comparator: Placebo
    • 2 x placebo injections on Day 1, then 1 placebo injection Q2W during 24 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Change from baseline to Week 24 in pre-bronchodilator FEV1
    • Time Frame: Baseline to Week 24
    • Absolute Change from baseline to Week 24 in pre-bronchodilator FEV1
  • Percent change from baseline to Week 24 in regional airway volumes corrected for lung volume ([s]iVaw) at total lung capacity (TLC)
    • Time Frame: Baseline to Week 24
    • Percent change from baseline to Week 24 in regional airway volumes corrected for lung volume ([s]iVaw) at total lung capacity (TLC)

Secondary Measures

  • Percent change from baseline to Week 24 in regional airway volumes corrected for lung volume ([s]iVaw) at functional residual capacity (FRC)
    • Time Frame: Baseline to Week 24
    • Percent change from baseline to Week 24 in regional airway volumes corrected for lung volume ([s]iVaw) at functional residual capacity (FRC)
  • Percent change from baseline to Week 24 in regional airway resistance corrected for lung volume ([s]iRaw) at TLC
    • Time Frame: Baseline to Week 24
    • Percent change from baseline to Week 24 in regional airway resistance corrected for lung volume ([s]iRaw) at TLC
  • Percent change from baseline to Week 24 in regional airway resistance corrected for lung volume ([s]iVaw) at functional residual capacity (FRC)
    • Time Frame: Baseline to Week 24
    • Percent change from baseline to Week 24 in regional airway resistance corrected for lung volume ([s]iRaw) at FRC
  • Change from baseline to Week 24 in lobar volumes (iVlobes) at TLC
    • Time Frame: Baseline to Week 24
    • Absolute change from baseline to Week 24 in lobar volumes (iVlobes) at TLC
  • Change from baseline to Week 24 in image-based ventilation/perfusion (iV/Q) at TLC
    • Time Frame: Baseline to Week 24
    • Absolute change from baseline to Week 24 in image-based ventilation/perfusion (iV/Q) at TLC
  • Change from baseline to Week 24 in HRCT-based internal airflow distribution (IAD)
    • Time Frame: Baseline to Week 24
    • Absolute Change from baseline to Week 24 in HRCT-based internal airflow distribution (IAD)
  • Change from baseline to Week 24 in FeNO
    • Time Frame: Baseline to Week 24
    • Absolute change from baseline to Week 24 in FeNO
  • Change from baseline to Week 24 in post-bronchodilator FEV1
    • Time Frame: Baseline to Week 24
    • Absolute change from baseline to Week 24 in post-bronchodilator FEV1
  • Achievement of FeNO <25 parts per billion (ppb) at Week 24
    • Time Frame: Baseline to Week 24
    • Achievement of FeNO <25 parts per billion (ppb) at Week 24
  • Change from baseline to Week 24 in ACQ-7
    • Time Frame: Baseline to Week 24
    • Absolute change from baseline to Week 24 in ACQ-7
  • Incidence of treatment emergent adverse events (TEAE) and serious adverse events (SAE) including clinically significant changes in vital signs and laboratory abnormalities
    • Time Frame: Baseline to Week 36
    • Proportion of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) including clinically significant changes in vital signs and laboratory abnormalities
  • Incidence of adverse events of special interest (AESI )
    • Time Frame: Baseline to Week 36
    • Proportion of participants with AESI (adverse events of special interest) -

Participating in This Clinical Trial

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
  • 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.

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
  • 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)
  • 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 patient 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 12 weeks before V1
  • Chronic treatment with oral corticosteroids (OCS) for more than 2 weeks before V1
  • Enrolled in other ongoing studies regardless of the investigational product
  • Treatment with an investigational drug within 8 weeks 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
  • Patients are dependent on the Sponsor or Investigator (in conjunction with Section 1.61 of the ICH GCP Ordinance E6)
  • Patients are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals
  • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study
  • Any country-related specific regulation that would prevent the subject from entering the study

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sanofi
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Clinical Sciences & Operations, Study Director, Sanofi
  • Overall Contact(s)
    • Trial Transparency email recommended (Toll free number for US & Canada), 800-633-1610, Contact-US@sanofi.com

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