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

NCT04400318 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: LPS15834U1111-1238-46792019-004647-74
• Study Type: interventional
• Target: 109
• Locations: 13 countries
• Sites: 65

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

Conditions

Asthma

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Achieved Fractional Exhaled Nitric Oxide (FeNO) Less Than (<) 25 Parts Per Billion (Ppb) at Week 24

  FeNO was analyzed using a NIOX instrument using a flow rate of 50 milliliters per second (mL/s). This assessment was conducted prior to spirometry and following a fast of greater than or equal to (≥1) hour. The test was performed after a wash out period of bronchodilators.

  Week 24

• Percent Change From Baseline to Week 24 in Untrimmed Distal Specific Airway Volumes ([s]iVaw) at Total Lung Capacity (TLC)

  Specific airway volume \[(s)iVaw\] is the change of volume of the airways (in mL), taking into account the lung volume changes (in liter \[L\]) as well. It corresponds to the ratio between the airway volume (iVaw) and the lobar volume. This way the air volumes are normalized across participants and become specific. Untrimmed distal \[s\]iVaw at TLC was assessed based on 3-dimensional (D) rendering of high-resolution computed tomography (HRCT) scans. Baseline was defined as the last available valid (non-missing) value up to and including the day of first dose of investigational medicinal product (IMP).

  Baseline (Day 1) to Week 24

Secondary Outcomes (11)

• Change From Baseline to Week 24 in Global Lung Mucus Score (University of California, San Francisco [UCSF] Mucus Scoring)

  Baseline (Day 1) to Week 24

• Percent Change From Baseline to Week 24 in Trimmed Distal Specific Airway Resistance ([s]iRaw) at TLC

  Baseline (Day 1) to Week 24

• Percent Change From Baseline to Week 24 in Untrimmed Distal Specific Airway Volumes ([s]iVaw) at Functional Residual Capacity (FRC)

  Baseline (Day 1) to Week 24

• Percent Change From Baseline to Week 24 in Trimmed Distal Specific Airway Resistance ([s]iRaw) at FRC

  Baseline (Day 1) to Week 24

• Percent Change From Baseline to Week 24 in Global Lung Lobar Volumes (iVlobes) at TLC

  Baseline (Day 1) to Week 24

Study Arms (2)

Dupilumab

EXPERIMENTAL

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.

Drug: Dupilumab

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Dupilumab DRUG

solution for injection subcutaneous

Also known as: SAR231893 Dupixent

Dupilumab

Placebo DRUG

Solution for injection subcutaneous

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (65)

Allianz Research Institute Site Number : 8400020

Westminster, California, 92683, United States

Location

University of Kansas School of Medicine Site Number : 8400008

Kansas City, Kansas, 66103, United States

Location

University of Michigan Site Number : 8400002

Ann Arbor, Michigan, 48109, United States

Location

The Lung Research Center Site Number : 8400010

Chesterfield, Missouri, 63017, United States

Location

American Health Research Site Number : 8400005

Charlotte, North Carolina, 28277, United States

Location

Velocity Clinical Research, Medford Site Number : 8400014

Medford, Oregon, 97504, United States

Location

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

Charleston, South Carolina, 29425, United States

Location

VitaLink Research-Greenville Site Number : 8400013

Greenville, South Carolina, 29615, United States

Location

VitaLink Research - Spartanburg Site Number : 8400011

Spartanburg, South Carolina, 29303, United States

Location

~Spartanburg Medical Research Site Number : 8400004

Spartanburg, South Carolina, 29303, United States

Location

Investigational Site Number : 1000013

Dupnitsa, 2600, Bulgaria

Location

Investigational Site Number : 1000004

Montana, 3403, Bulgaria

Location

Investigational Site Number : 1000018

Plovdiv, 4000, Bulgaria

Location

Investigational Site Number : 1000012

Plovdiv, 4002, Bulgaria

Location

Investigational Site Number : 1000008

Rousse, 7002, Bulgaria

Location

Investigational Site Number : 1000015

Sofia, 1000, Bulgaria

Location

Investigational Site Number : 1000005

Sofia, 1202, Bulgaria

Location

Investigational Site Number : 1000003

Sofia, 1233, Bulgaria

Location

Investigational Site Number : 1000006

Sofia, 1233, Bulgaria

Location

Investigational Site Number : 1000011

Sofia, 1407, Bulgaria

Location

Investigational Site Number : 1000010

Sofia, 1431, Bulgaria

Location

Investigational Site Number : 1000002

Sofia, 1680, Bulgaria

Location

Investigational Site Number : 1000007

Stara Zagora, 6001, Bulgaria

Location

Investigational Site Number : 2080006

Aarhus N, 8200, Denmark

Location

Investigational Site Number : 2080002

Copenhagen, 2100, Denmark

Location

Investigational Site Number : 2080003

Copenhagen Nv, 2400, Denmark

Location

Investigational Site Number : 2080001

Hvidovre, 2650, Denmark

Location

Investigational Site Number : 2500001

Montpellier, France

Location

Investigational Site Number : 3800003

Cona, Ferrara, 44124, Italy

Location

Investigational Site Number : 3800004

Rozzano, Milano, 20089, Italy

Location

Investigational Site Number : 3800001

Pisa, 56124, Italy

Location

Investigational Site Number : 6200004

Coimbra, 3000-075, Portugal

Location

Investigational Site Number : 6200005

Guimarães, 4810-061, Portugal

Location

Investigational Site Number : 6200006

Lisbon, 1649-035, Portugal

Location

Investigational Site Number : 6200003

Porto, 4100-180, Portugal

Location

Investigational Site Number : 6200001

Porto, 4202-451, Portugal

Location

Investigational Site Number : 6420005

Bragadiru, 769764, Romania

Location

Investigational Site Number : 6420008

Brasov, 500283, Romania

Location

Investigational Site Number : 6420006

Cluj-Napoca, 400275, Romania

Location

Investigational Site Number : 6420001

Cluj-Napoca, 400371, Romania

Location

Investigational Site Number : 6420007

Oradea, 410155, Romania

Location

Investigational Site Number : 6420003

Timișoara, 300134, Romania

Location

Investigational Site Number : 6820008

Dammam, 31952, Saudi Arabia

Location

Investigational Site Number : 6820004

Jeddah, 21423, Saudi Arabia

Location

Investigational Site Number : 6820006

Riyadh, 11426, Saudi Arabia

Location

Investigational Site Number : 6820001

Riyadh, 11525, Saudi Arabia

Location

Investigational Site Number : 6820002

Riyadh, 12372, Saudi Arabia

Location

Investigational Site Number : 6820010

Riyadh, 12746, Saudi Arabia

Location

Investigational Site Number : 7240001

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number : 7240002

Santiago de Compostela, Galicia [Galicia], 15706, Spain

Location

Investigational Site Number : 7240005

Madrid, Madrid, Comunidad de, 28041, Spain

Location

Investigational Site Number : 7240003

Madrid, Madrid, Comunidad de, 28046, Spain

Location

Investigational Site Number : 7520001

Lund, 221 85, Sweden

Location

Investigational Site Number : 1580004

Kaohsiung City, 807, Taiwan

Location

Investigational Site Number : 1580002

Taichung, 40447, Taiwan

Location

Investigational Site Number : 1580003

Tainan, 704, Taiwan

Location

Investigational Site Number : 1580001

Taipei, 110, Taiwan

Location

Investigational Site Number : 8040003

Chernivtsi, 58001, Ukraine

Location

Investigational Site Number : 8040001

Ivano-Frankivsk, 76018, Ukraine

Location

Investigational Site Number : 8040002

Kharkiv, 61124, Ukraine

Location

Investigational Site Number : 8040004

Kyiv, 01023, Ukraine

Location

Investigational Site Number : 8040005

Odesa, 65025, Ukraine

Location

Investigational Site Number : 8040007

Ternopil, 46000, Ukraine

Location

Investigational Site Number : 8260001

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

Investigational Site Number : 8260002

Bradford, BD9 6RJ, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 41145399 DERIVED

• 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.

  PMID: 39947221 DERIVED

Related Links

• LPS15834 Plain Language Results Summary

MeSH Terms

Conditions

Asthma

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2020
• First Posted: May 22, 2020
• Study Start: June 20, 2020
• Primary Completion: June 26, 2023
• Study Completion: August 21, 2023
• Last Updated: September 9, 2025
• Results First Posted: July 10, 2024

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

BU (13); IT (3); DK (4); SA (6); ES (4); SE (1); RO (6); FR (1); UA (6); GB (2); TW (4); US (10); PT (5)