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

NCT ID: NCT04400318

Last Updated: 2025-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-20
• Study Completion Date: 2023-08-21

Brief 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

Detailed Description

The study duration for each participant was a total of minimum 29 weeks and up to 41 weeks. This included 4 weeks +/-1 week screening period, 24 weeks of treatment period and a follow-up period up to 12 weeks or until the participants switched to commercialized dupilumab (or other biologic products), whatever came first.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Dupilumab

Participants received a loading dose of dupilumab 600 mg as 2 subcutaneous (SC) injections on Day 1, followed by a single dupilumab 300 mg SC injection Q2W for 24 weeks along with a stable dose of medium to high ICS dose in combination with a second controller medication +/- a third controller.

Group Type: EXPERIMENTAL

Dupilumab

Intervention Type: DRUG

solution for injection subcutaneous

Placebo

Participants received placebo matched to dupilumab as 2 x 2 mL SC injections on Day 1, followed by a single SC injection Q2W for 24 weeks along with a stable dose of medium to high ICS dose in combination with a second controller medication +/- a third controller.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Solution for injection subcutaneous

Interventions

Dupilumab

solution for injection subcutaneous

Intervention Type: DRUG

Placebo

Solution for injection subcutaneous

Intervention Type: DRUG

Other Intervention Names

SAR231893 Dupixent

Eligibility 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 visit (V)1 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 V1:

• 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 V1
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Allianz Research Institute Site Number : 8400020

Westminster, California, United States

University of Kansas School of Medicine Site Number : 8400008

Kansas City, Kansas, United States

University of Michigan Site Number : 8400002

Ann Arbor, Michigan, United States

The Lung Research Center Site Number : 8400010

Chesterfield, Missouri, United States

American Health Research Site Number : 8400005

Charlotte, North Carolina, United States

Velocity Clinical Research, Medford Site Number : 8400014

Medford, Oregon, United States

Medical University of South Carolina - Pulmonary & Critical Care Clinical Research Program Site Number : 8400009

Charleston, South Carolina, United States

VitaLink Research-Greenville Site Number : 8400013

Greenville, South Carolina, United States

VitaLink Research - Spartanburg Site Number : 8400011

Spartanburg, South Carolina, United States

~Spartanburg Medical Research Site Number : 8400004

Spartanburg, South Carolina, United States

Investigational Site Number : 1000013

Dupnitsa, , Bulgaria

Investigational Site Number : 1000004

Montana, , Bulgaria

Investigational Site Number : 1000018

Plovdiv, , Bulgaria

Investigational Site Number : 1000012

Plovdiv, , Bulgaria

Investigational Site Number : 1000008

Rousse, , Bulgaria

Investigational Site Number : 1000015

Sofia, , Bulgaria

Investigational Site Number : 1000005

Sofia, , Bulgaria

Investigational Site Number : 1000003

Sofia, , Bulgaria

Investigational Site Number : 1000006

Sofia, , Bulgaria

Investigational Site Number : 1000011

Sofia, , Bulgaria

Investigational Site Number : 1000010

Sofia, , Bulgaria

Investigational Site Number : 1000002

Sofia, , Bulgaria

Investigational Site Number : 1000007

Stara Zagora, , Bulgaria

Investigational Site Number : 2080006

Aarhus N, , Denmark

Investigational Site Number : 2080002

Copenhagen, , Denmark

Investigational Site Number : 2080003

Copenhagen Nv, , Denmark

Investigational Site Number : 2080001

Hvidovre, , Denmark

Investigational Site Number : 2500001

Montpellier, , France

Investigational Site Number : 3800003

Cona, Ferrara, Italy

Investigational Site Number : 3800004

Rozzano, Milano, Italy

Investigational Site Number : 3800001

Pisa, , Italy

Investigational Site Number : 6200004

Coimbra, , Portugal

Investigational Site Number : 6200005

Guimarães, , Portugal

Investigational Site Number : 6200006

Lisbon, , Portugal

Investigational Site Number : 6200003

Porto, , Portugal

Investigational Site Number : 6200001

Porto, , Portugal

Investigational Site Number : 6420005

Bragadiru, , Romania

Investigational Site Number : 6420008

Brasov, , Romania

Investigational Site Number : 6420006

Cluj-Napoca, , Romania

Investigational Site Number : 6420001

Cluj-Napoca, , Romania

Investigational Site Number : 6420007

Oradea, , Romania

Investigational Site Number : 6420003

Timișoara, , Romania

Investigational Site Number : 6820008

Dammam, , Saudi Arabia

Investigational Site Number : 6820004

Jeddah, , Saudi Arabia

Investigational Site Number : 6820006

Riyadh, , Saudi Arabia

Investigational Site Number : 6820001

Riyadh, , Saudi Arabia

Investigational Site Number : 6820002

Riyadh, , Saudi Arabia

Investigational Site Number : 6820010

Riyadh, , Saudi Arabia

Investigational Site Number : 7240001

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number : 7240002

Santiago de Compostela, Galicia [Galicia], Spain

Investigational Site Number : 7240005

Madrid, Madrid, Comunidad de, Spain

Investigational Site Number : 7240003

Madrid, Madrid, Comunidad de, Spain

Investigational Site Number : 7520001

Lund, , Sweden

Investigational Site Number : 1580004

Kaohsiung City, , Taiwan

Investigational Site Number : 1580002

Taichung, , Taiwan

Investigational Site Number : 1580003

Tainan City, , Taiwan

Investigational Site Number : 1580001

Taipei, , Taiwan

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 : 8040005

Odesa, , Ukraine

Investigational Site Number : 8040007

Ternopil, , Ukraine

Investigational Site Number : 8260001

Leicester, Leicestershire, United Kingdom

Investigational Site Number : 8260002

Bradford, , United Kingdom

Countries

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

References

Porsbjerg C, Dunican EM, Lugogo NL, Castro M, Papi A, Backer V, Brightling CE, Bourdin A, Virchow JC, Zhang M, Soler X, Rowe PJ, Deniz Y, de Prado Gomez L, Sacks HJ, Jacob-Nara JA. Effect of Dupilumab on Mucus Burden in Patients with Moderate-to-Severe Asthma: The VESTIGE Trial. Am J Respir Crit Care Med. 2025 Oct 27. doi: 10.1164/rccm.202410-1894OC. Online ahead of print.

Reference Type: DERIVED

PMID: 41145399 (View on PubMed)

Castro M, Papi A, Porsbjerg C, Lugogo NL, Brightling CE, Gonzalez-Barcala FJ, Bourdin A, Ostrovskyy M, Staevska M, Chou PC, Duca L, Pereira AM, Fogarty C, Nadama R, Zhang M, Rodrigues A, Soler X, Sacks HJ, Deniz Y, Rowe PJ, de Prado Gomez L, Jacob-Nara JA. Effect of dupilumab on exhaled nitric oxide, mucus plugs, and functional respiratory imaging in patients with type 2 asthma (VESTIGE): a randomised, double-blind, placebo-controlled, phase 4 trial. Lancet Respir Med. 2025 Mar;13(3):208-220. doi: 10.1016/S2213-2600(24)00362-X. Epub 2025 Feb 10.

Reference Type: DERIVED

PMID: 39947221 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.trialsummaries.com/Study/StudyDetails?id=25276&tenant=MT_SNY_9011

LPS15834 Plain Language Results Summary

Other Identifiers

U1111-1238-4679

Identifier Type: REGISTRY

Identifier Source: secondary_id

2019-004647-74

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LPS15834

Identifier Type: -

Identifier Source: org_study_id