A Study to Evaluate the Effect of Dupilumab on Exercise Capacity in Adult Patients With Asthma

A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Effect of Dupilumab on Exercise Capacity in Patients With Moderate-to-Severe Asthma

The primary objective of the study is to demonstrate that dupilumab treatment improves exercise capacity in patients with moderate-to-severe asthma.

The secondary objectives of the study are:

• To demonstrate that dupilumab treatment increases physical activity of daily living in patients with moderate-to-severe asthma
• To demonstrate that dupilumab treatment improves pre- and post-exercise lung function in patients with moderate-to-severe asthma

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: dupilumab; Drug: Matching placebo

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67091
    • CHU de Strasbourg - Nouvel Hôpital Civil
  • Bourgogne
    • Dijon, Bourgogne, France, 21000
      • Chu Dijon
  • Marne
    • Reims, Marne, France, 51092
      • CHU Reims
• Germany
  • Berlin, Germany, 12159
    • Regeneron Study Site
  • Bavaria
    • Aschaffenburg, Bavaria, Germany, 63739
      • Praxis Dr. M. Rolke u. Dr. P. Rueckert
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60389
      • Regeneron Study Site
    • Frankfurt am Main, Hessen, Germany, 60596
      • IKF Pneumologie GmbH & Co. KG - Institut fuer klinische Forschung Pneumologie Frankfurt (Clinical Research Centre Respiratory Medicine) to IKF Pneumologie Frankfurt GmbH & Co KG.
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • Regeneron Study Site
  • Rheinland-Pfalz
    • Koblenz, Rheinland-Pfalz, Germany, 56068
      • Regeneron Study Site
    • Mainz, Rheinland-Pfalz, Germany, 55128
      • IKF Pneumologie Mainz, Helix Medical Excellence Center Mainz
  • Schleswig-Holstein
    • Grosshansdorf, Schleswig-Holstein, Germany, 22977
      • Regeneron Study Site
    • Luebeck, Schleswig-Holstein, Germany, 486344
      • KLB - Gesundheitsforschung Luebeck GmbH
• Poland
  • Bialystok, Poland, 15-044
    • Centrum Medycyny Oddechowej, Mroz Spolka Jawna
  • Wroclaw, Poland, 54-239
    • Lekarze Specjalisci - J. Malolepszy I Partnerzy
  • Dolnoslaskie
    • Lubin, Dolnoslaskie, Poland, 59-300
      • Regeneron Study Site
• Spain
  • Barcelona, Spain, 08907
    • Hospital Universitario de Bellvitge
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon (HGUGM) - Instituto de Investigacion Sanitaria Gregorio Maranon (IiSGM)
• United States
  • California
    • Rolling Hills Estates, California, United States, 90274
      • Palos Verdes Medical Group (PVMG); Peninsula Research Associates (PRA)
    • Torrance, California, United States, 90509
      • UCLA Medical Center - Harbor
    • Westminster, California, United States, 92683
      • Allianz Research Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics-Roy J. and Lucille A. Carver College of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Infinity Medical Research
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • American Health Research
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • UH Cleveland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • Tennessee
    • Hendersonville, Tennessee, United States, 37075
      • Regeneron Study Site
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Medical School at Houston
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• A physician diagnosis of asthma
• Pre-bronchodilator FEV1 between 30% and 75% predicted at both the screening and baseline visits
• Bronchodilator reversibility defined as >200 mL and 12% increase in FEV1 post-administration of a short-acting beta agonist (SABA). A patient may also qualify if there is a documented history of bronchodilator reversibility or positive methacholine challenge test within 12 months prior to the screening visit
• Stable background therapy for at least 3 months with a stable dose ≥4 weeks prior to the baseline visit of a medium-to-high dose ICS (fluticasone propionate ≥250 to 1000 μg twice daily [BID] or equivalent) in combination with at least a second controller medication (eg, long-acting beta agonist [LABA], long-acting muscarinic antagonist [LAMA], leukotriene receptor antagonist [LTRA], theophylline, etc.); a third controller is allowed and with the same stabilization requirements
• Blood eosinophil count ≥300 cells/μL for patients not on maintenance OCS at the screening visit
• ACQ-5 score ≥1.5 at the screening and baseline visits

Key Exclusion Criteria:

• Body mass index >35 kg/m2 at screening
• Current smoking, vaping or tobacco chewing or cessation of any of these within 6 months prior to randomization, or >10 pack years smoking history
• Patients who require supplemental oxygen at screening
• Clinically significant cardiac disease as described in the protocol
• Uncontrolled hypertension at screening or baseline
• Participation in exercise or physical rehabilitation program within last 6 months prior to screening or planned during the study
• Previous use of dupilumab
• Anti-IgE therapy (eg, omalizumab [Xolair®]) within 130 days prior to visit 1 or any other biologic therapy (including anti-IL5, anti-IL-5R, anti-IL4Rα, anti-IL-13 mAb) or systemic immunosuppressant (eg, methotrexate, any anti-tumor necrosis factor mAbs, Janus kinase inhibitors, B- and/or T-cell targeted immunosuppressive therapies) to treat inflammatory disease or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis) and other diseases, within 3 months or 5 half-lives prior to screening, whichever is longer
• Exposure to another investigative drug (monoclonal antibodies as well as small molecules) within a period prior to screening, of <3 months or <5 half-lives (whichever is longer)
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study
• Women of childbearing potential (WOCBP)* who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 12 weeks after the last dose

NOTE: Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dupilumab; A loading dose at the start of the treatment followed by once every two weeks (Q2W).	Drug: dupilumab; Pre-filled syringe administered by subcutaneous (SC) injections; Other Names: SAR231893; Dupixent®
Experimental: Matching placebo; Matching dupilumab	Drug: Matching placebo; Pre-filled syringe administered by subcutaneous (SC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 in Constant Work Rate Exercise Endurance Time - CWRET (Constant Work Rate Exercise Test)	CWRET (Constant Work Rate Exercise Test) will be performed on an electromagnetically-braked cycle ergometer in an exercise physiology laboratory overseen by a trained pulmonologist or medical doctor designee.	Up to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 in Average Number of Steps Walked Per Day	Based on accelerometry data	Up to week 12
Change From Baseline to Week 12 in Total Energy Expenditure	Metabolic equivalents of tasks [METs]. Based on accelerometry data	Up to week 12
Change From Baseline to Week 12 in the Mean Duration of Moderate-to-vigorous Physical Activity	Defined as ≥3 METs. Based on accelerometry data	Up to week 12
Change From Baseline to Week 12 in Pre- and Post-exercise Forced Expiratory Volume in One Second (FEV1)	Based on spirometry data	Up to week 12

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trials Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2020
• Primary Completion (Actual): July 15, 2023
• Study Completion (Actual): July 15, 2023

Study Registration Dates

• First Submitted: December 17, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 18, 2019

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: R668-AS-1903; 2019-002742-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
• IPD Sharing Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (eg, FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No