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

Asthma Clinical Trial

— VESTIGE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04400318
• Other study ID #: LPS15834
• Secondary ID: U1111-1238-46792
• Status: Completed
• Phase: Phase 4
• Start date: June 22, 2020
• Est. completion date: August 21, 2023

Study information

• Verified date: November 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: August 21, 2023
• Est. primary completion date: June 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

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 participants 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, hepatic, 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 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

• Participants are dependent on the Sponsor or Investigator (in conjunction with Section 1.61 of the ICH GCP Ordinance E6)

• Participants 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.

Related Conditions & MeSH terms

• Asthma
• Inflammation

Intervention

Drug:
• Dupilumab
solution for injection subcutaneous
• Placebo
Solution for injection subcutaneous

Locations

Country	Name	City	State
Bulgaria	Investigational Site Number : 1000013	Dupnitsa
Bulgaria	Investigational Site Number : 1000004	Montana
Bulgaria	Investigational Site Number : 1000012	Plovdiv
Bulgaria	Investigational Site Number : 1000018	Plovdiv
Bulgaria	Investigational Site Number : 1000008	Ruse
Bulgaria	Investigational Site Number : 1000002	Sofia
Bulgaria	Investigational Site Number : 1000003	Sofia
Bulgaria	Investigational Site Number : 1000005	Sofia
Bulgaria	Investigational Site Number : 1000006	Sofia
Bulgaria	Investigational Site Number : 1000010	Sofia
Bulgaria	Investigational Site Number : 1000011	Sofia
Bulgaria	Investigational Site Number : 1000015	Sofia
Bulgaria	Investigational Site Number : 1000007	Stara Zagora
Denmark	Investigational Site Number : 2080004	Aalborg
Denmark	Investigational Site Number : 2080006	Aarhus N
Denmark	Investigational Site Number : 2080002	Copenhagen
Denmark	Investigational Site Number : 2080003	Copenhagen Nv
Denmark	Investigational Site Number : 2080005	Hellerup
Denmark	Investigational Site Number : 2080001	Hvidovre
France	Investigational Site Number : 2500002	Lyon
France	Investigational Site Number : 2500001	Montpellier
Italy	Investigational Site Number : 3800003	Cona	Ferrara
Italy	Investigational Site Number : 3800001	Pisa
Italy	Investigational Site Number : 3800004	Rozzano	Milano
Portugal	Investigational Site Number : 6200004	Coimbra
Portugal	Investigational Site Number : 6200005	Guimarães
Portugal	Investigational Site Number : 6200006	Lisboa
Portugal	Investigational Site Number : 6200001	Porto
Portugal	Investigational Site Number : 6200003	Porto
Romania	Investigational Site Number : 6420005	Bragadiru
Romania	Investigational Site Number : 6420008	Brasov
Romania	Investigational Site Number : 6420001	Cluj-Napoca
Romania	Investigational Site Number : 6420006	Cluj-Napoca
Romania	Investigational Site Number : 6420007	Oradea
Romania	Investigational Site Number : 6420003	Timisoara
Saudi Arabia	Investigational Site Number : 6820008	Dammam
Saudi Arabia	Investigational Site Number : 6820004	Jeddah
Saudi Arabia	Investigational Site Number : 6820001	Riyadh
Saudi Arabia	Investigational Site Number : 6820002	Riyadh
Saudi Arabia	Investigational Site Number : 6820006	Riyadh
Saudi Arabia	Investigational Site Number : 6820010	Riyadh
Spain	Investigational Site Number : 7240001	Barcelona
Spain	Investigational Site Number : 7240003	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240004	Madrid
Spain	Investigational Site Number : 7240005	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240002	Santiago de Compostela	Galicia [Galicia]
Sweden	Investigational Site Number : 7520001	Lund
Taiwan	Investigational Site Number : 1580004	Kaohsiung
Taiwan	Investigational Site Number : 1580002	Taichung
Taiwan	Investigational Site Number : 1580003	Tainan
Taiwan	Investigational Site Number : 1580001	Taipei
Ukraine	Investigational Site Number : 8040003	Chernivtsi
Ukraine	Investigational Site Number : 8040001	Ivano-Frankivsk
Ukraine	Investigational Site Number : 8040002	Kharkiv
Ukraine	Investigational Site Number : 8040004	Kyiv
Ukraine	Investigational Site Number : 8040006	Kyiv
Ukraine	Investigational Site Number : 8040005	Odesa
Ukraine	Investigational Site Number : 8040007	Ternopil
United Kingdom	Investigational Site Number : 8260002	Bradford
United Kingdom	Investigational Site Number : 8260001	Leicester	Leicestershire
United States	University of Michigan Site Number : 8400002	Ann Arbor	Michigan
United States	Medical University of South Carolina - Pulmonary & Critical Care Clinical Research Program Site Number : 8400009	Charleston	South Carolina
United States	American Health Research Site Number : 8400005	Charlotte	North Carolina
United States	The Lung Research Center Site Number : 8400010	Chesterfield	Missouri
United States	VitaLink Research-Greenville Site Number : 8400013	Greenville	South Carolina
United States	University of Kansas School of Medicine Site Number : 8400008	Kansas City	Kansas
United States	Velocity Clinical Research, Medford Site Number : 8400014	Medford	Oregon
United States	~Spartanburg Medical Research Site Number : 8400004	Spartanburg	South Carolina
United States	VitaLink Research - Spartanburg Site Number : 8400011	Spartanburg	South Carolina
United States	Allianz Research Institute Site Number : 8400020	Westminster	California

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Bulgaria,  Denmark,  France,  Italy,  Portugal,  Romania,  Saudi Arabia,  Spain,  Sweden,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants achieving FeNO <25 parts per billion (ppb) at Week 24	Proportion of participants achieving FeNO <25 parts per billion (ppb) at Week 24	Week 24
Primary	Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at total lung capacity (TLC)	Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at total lung capacity (TLC).	Baseline to Week 24
Secondary	Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at functional residual capacity (FRC)	Percent change from baseline to Week 24 in untrimmed distal airway volumes corrected for lung volume ([s]iVaw) at functional residual capacity (FRC).	Baseline to Week 24
Secondary	Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at TLC	Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at TLC.	Baseline to Week 24
Secondary	Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at FRC	Percent change from baseline to Week 24 in untrimmed distal airway resistance corrected for lung volume ([s]iRaw) at FRC.	Baseline to Week 24
Secondary	Change from baseline to Week 24 in global lung lobar volumes (iVlobes) at TLC	Absolute change from baseline to Week 24 in global lung lobar volumes (iVlobes) at TLC.	Baseline to Week 24
Secondary	Change from baseline to Week 24 in HRCT-based internal airflow distribution (IAD) for each lung zone	Absolute Change from baseline to Week 24 in HRCT-based internal airflow distribution (IAD) for each lung zone.	Baseline to Week 24
Secondary	Change from baseline to Week 24 in image-based ventilation/perfusion (iV/Q) at TLC for each lung zone	Absolute change from baseline to Week 24 in image-based ventilation/perfusion (iV/Q) at TLC for each lung zone.	Baseline to Week 24
Secondary	Change from baseline to Week 24 in global lung mucus scoring (UCSF mucus scoring)	University of California, San Francisco (UCSF) mucus scoring is a scoring system to quantify mucus plugs in lung images generated using computerized tomography. The scoring system is based on bronchopulmonary segmental anatomy. Each bronchopulmonary segment is given a score of 1 (mucus plug(s) present) or 0 (mucus plug(s) absent). The segment scores of each lobe are summed to generate a total mucus score for both lungs, yielding a mucus score ranging from 0-20.	Baseline to Week 24
Secondary	Change from baseline to Week 24 in FeNO	Absolute change from baseline to Week 24 in FeNO.	Baseline to Week 24
Secondary	Change from baseline to Week 24 in pre-bronchodilator FEV1	Change from baseline to Week 24 in pre-bronchodilator FEV1	Week 24
Secondary	Change from baseline to Week 24 in post-bronchodilator FEV1	Change from baseline to Week 24 in post-bronchodilator FEV1.	Baseline to Week 24
Secondary	Change from baseline to Week 24 in Asthma Control Questionnaire 7 (ACQ-7)	The ACQ-7 is a validated asthma assessment tool that consists of 6 self-assessment questions. The overall scale ranges from 0 = 'totally controlled' to 6 = 'severely uncontrolled.	Baseline to Week 24
Secondary	Incidence of treatment emergent adverse events (TEAE) and serious adverse events (SAE) including clinically significant changes in vital signs and laboratory abnormalities	The incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) including clinically significant changes in vital signs and laboratory abnormalities.	Baseline to Week 36
Secondary	Incidence of adverse events of special interest (AESI )	The incidence of AESI.	Baseline to Week 36