Efficacy of Dupilumab Added to Medium Dose Inhaled Corticosteroid/Long-acting Beta-agonist (ICS/LABA) in Comparison to ICS Dose Escalation to High Dose ICS/LABA in Adolescent and Adult Patients With Uncontrolled Asthma (AIM4:Next Step)

AIM4: Next Step - Asthma Uncontrolled With ICS in Medium Dose (GINA 4): Next Step; Efficacy of Dupilumab Added to Medium Dose ICS/LABA in Comparison to ICS Dose Escalation to High Dose ICS/LABA in Patients With Uncontrolled Asthma

This study is researching a drug called dupilumab. The study is focused on patients who have uncontrolled asthma. Asthma is a condition where the airways narrow and swell, making it difficult to breathe. Uncontrolled asthma means that patients are still having frequent symptoms while taking their current asthma medication.

The aim of the study is to see which regimen is more effective: taking dupilumab with an inhaled asthma medication or only taking a higher dose of the inhaled asthma medication. The type of asthma medication that will be used is a combination inhaled corticosteroid and long-acting beta-agonist (referred to as an ICS/LABA). Some patients may also receive an additional asthma medication called a long-acting muscarinic antagonist (referred to as a LAMA) if they are already receiving a LAMA.

The study is also looking at:

• What side effects may happen from taking dupilumab

Study Overview

• Status: Active, not recruiting
• Conditions: Asthma
• Intervention / Treatment: Drug: dupilumab; Drug: Matching Placebo; Drug: ICS/LABA

Detailed Description

This study is a Phase 3b in Canada Minors will not be enrolled in Denmark

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4W2
    • Clinique de Specialisee en Allergie de la Capitale
  • Québec, Canada, G1V 4G5
    • Institut Universitare de Cardiologie et de Pneumologie de Quebec (IUCPQ) - Universite Laval
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • The Lung Centre at Vancouver General Hospital
  • Ontario
    • Ajax, Ontario, Canada, L1S 2J5
      • Dynamic Drug Advancement Ltd.
    • Toronto, Ontario, Canada, M5T 3A9
      • Inspiration Research Limited
    • Toronto, Ontario, Canada, M5G 1E2
      • Evidence Based Medical Educator Inc.
    • Windsor, Ontario, Canada, N8X 1T3
      • Dr. Syed Anees Medicine Professional Corporation
• Denmark
  • Region Syddanmark
    • Vejle, Region Syddanmark, Denmark, 7100
      • Vejle Sygehus
• Germany
  • Berlin, Germany, 10717
    • Lungenpraxis Hohenzollerndamm RCMS
  • Leipzig, Germany, 04347
    • POIS Sachsen GmbH iG
  • Mainz, Germany, 55128
    • IKF Pneumologie GmbH & Co. KG
  • Bavaria
    • Augsburg, Bavaria, Germany, 86150
      • Praxis fur Pneumologie am Duako
    • Munich, Bavaria, Germany, 81377
      • LMU University Hospital Munich
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60596
      • IKF Pneumologie Frankfurt GmbH & Co KG
  • Rhineland-Palatinate
    • Koblenz, Rhineland-Palatinate, Germany, 56068
      • KPPK Studienzentrum
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23552
      • Velocity Clinical Research Lubeck GmbH (Formerly KLB Gesundheitsforschung Lübeck GmbH)
• Poland
  • Wroclaw, Poland, 54239
    • Lekarze Specjaliści Małolepszy i Partnerzy
  • Wroclaw, Poland, PL-53-201
    • ALL-MED Specjalistyczna Opieka Medyczna Medyczny Instytut Badawczy
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 30-033
      • Centrum Medyczne ALL-MED
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 53301
      • Michał Bogacki - DOBROSTAN
  • Malopolska
    • Krakow, Malopolska, Poland, 31-559
      • Diamond Clinic sp zoo
  • Mazovian
    • Warsaw, Mazovian, Poland, 02-677
      • European Trial Group (ETG) Warsaw
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-044
      • Centrum Medycyny Oddechowej Mroz SJ
    • Bialystok, Podlaskie Voivodeship, Poland, 15-687
      • Allergy Clinic NZOZ Homeo Medicus
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-214
      • Uniwersyteckie Centrum Kliniczne, Budynek Centrum Medycyny Nieinwazyjnej
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • PRCCI Clinical Research Center
• United States
  • California
    • Bakersfield, California, United States, 93301
      • Kern Research, Inc
    • La Jolla, California, United States, 92037
      • Modena Allergy & Asthma, Inc.
    • Lancaster, California, United States, 93534
      • Antelope Valley Clinical Trials
    • Long Beach, California, United States, 90815
      • Ark Clinical Research, LLC
    • Newport Beach, California, United States, 92663
      • Newport Native Md, Inc.
    • Orange, California, United States, 92868
      • Childrens Hospital of Orange County Main Campus
    • Santa Monica, California, United States, 90404
      • Raffi Tachdjian MD, Inc.
    • Stockton, California, United States, 95207
      • Bensch Clinical Research
    • Upland, California, United States, 91786
      • Integrated Research of Inland, Inc.
    • Westminster, California, United States, 92683
      • Allianz Research Institute
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Clearwater, Florida, United States, 33765
      • St Francis Medical Institute
    • Kissimmee, Florida, United States, 34746
      • Florida Lung, Asthma and Sleep Specialists (FLASS) - Celebration
    • Winter Park, Florida, United States, 32789
      • Clinical Site Partners, LLC dba Flourish Research
  • Idaho
    • Boise, Idaho, United States, 83706
      • Treasure Valley Medical Research
  • Illinois
    • Normal, Illinois, United States, 61761
      • Sneeze Wheeze and Itch Associates
    • River Forest, Illinois, United States, 60305
      • Asthma and Allergy Center of Chicago
    • Skokie, Illinois, United States, 60077
      • Endeavor Health, Skokie Campus
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Bluegrass Allergy Research
    • Louisville, Kentucky, United States, 40217
      • Family Allergy and Asthma Research Institute
    • Owensboro, Kentucky, United States, 42301
      • Allergy & Asthma Specialists, P.S.C.
  • Maine
    • Bangor, Maine, United States, 04401
      • Paul A. Shapero, M.D.
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute, Inc.
  • Missouri
    • St Louis, Missouri, United States, 63119
      • Washington University School of Medicine
  • Montana
    • Missoula, Montana, United States, 59808
      • Montana Medical Research
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • The Asthma and Allergy Center
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Henderson Clinical Trials
  • New York
    • Cortland, New York, United States, 13045
      • Certified Research Associates
    • Hawthorne, New York, United States, 10532
      • New York Medical College
    • New York, New York, United States, 10016
      • Northwell Health at ENT & Allergy Associates
    • Rochester, New York, United States, 14607
      • Rochester Regional Health - Alexander Park - Allergy, Immunology & Rheumatology
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Childrens Hospital and Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Allergy Asthma and Clinical Research Center
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • Clinical Research Associates of Central PA
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Asthma and Environmental Health Lung Institute
    • Wynnewood, Pennsylvania, United States, 19096
      • Pulmonology Associates Inc.
  • Texas
    • Dallas, Texas, United States, 75235
      • Dharma MD PA d/b/a Southwest Family Medicine Associates
    • Denison, Texas, United States, 75020
      • Premier Pulmonary Critical Care and Sleep Medicine
    • El Paso, Texas, United States, 79912
      • Western Sky Medical Research
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Section of Pulmonary and Critical Care
    • McKinney, Texas, United States, 75069
      • Metroplex Pulmonary and Sleep Center, PA
    • North Richland Hills, Texas, United States, 76180
      • Lung Sleep Research Institute
    • San Antonio, Texas, United States, 78229
      • South Texas Allergy & Asthma Medical Professionals (STAAMP) Research
    • Waco, Texas, United States, 76712
      • Allergy & Asthma Care of Waco
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center - Murray (Pulmonary Medicine)
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Diagnosis of asthma for ≥12 months, based on the Global Initiative for Asthma (GINA) 2023 guidance document
2. Existing treatment with medium dose ICS/LABA (>250 to 500 μg/day of fluticasone propionate DPI or equivalent, per GINA 2023 guidance document) for at least 3 months with a stable dose ≥1 month prior to visit 1
3. Participants requiring a maximum of 3 controllers for their asthma will be considered eligible for this study
4. Pre-bronchodilator FEV1, as defined in the protocol
5. Reversibility of at least 12% and 200 mL in FEV1 after the administration of 200 to 400 μg albuterol/salbutamol at screening OR a documented history of ≥20% reduction in the FEV1, as defined in the protocol
6. Demonstrated adherence to medium dose ICS/LABA on at least 80% of days during the run-in period
7. ACQ-5 score ≥1.5 at screening (visit 1)
8. History of ≥1 severe exacerbation(s) in the previous year before visit 1, but not in the 30 days immediately preceding visit 1
9. Biomarker criteria: Baseline blood eosinophil count ≥300 cells/μL at visit 1 (~90% of population), as defined in the protocol

Key Exclusion Criteria:

1. Diagnosis of chronic obstructive pulmonary disease (COPD) or other lung diseases which may impair lung function and interfere with treatment assessments
2. Clinical evidence of lung disease(s) other than asthma or imaging (Chest X-ray, computed tomography (CT), magnetic resonance imaging [MRI]) with significant findings within 12 months of visit 1 and up to and including the baseline visit (visit 3)
3. A participant who experiences a severe asthma exacerbation at any time from 1 month prior to the screening visit (visit 1) up to and including the baseline visit (visit 3), as defined in the protocol
4. Weight is less than 30 kilograms
5. Current smoker or cessation of smoking within 6 months prior to visit 1 or previous smoker with a smoking history ≥10 pack-years
6. Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the participant's participation in the study, as defined in the protocol
7. Participants cannot be on systemic corticosteroids at any time from 1 month prior to the screening visit (visit 1) through the duration of the run-in period

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 + ICS/LABA; Randomized 1:1	Drug: dupilumab; Administered by subcutaneous (SC) injection; Other Names: REGN668; SAR231893; Dupixent®; Drug: ICS/LABA; Administered at a blinded dose; Other Names: fluticasone; propionate/salmeterol HFA; inhalation aerosol
Placebo Comparator: Placebo + ICS/LABA; Randomized 1:1	Drug: Matching Placebo; Administered by SC injection; Drug: ICS/LABA; Administered at a blinded dose; Other Names: fluticasone; propionate/salmeterol HFA; inhalation aerosol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Annualized severe asthma exacerbation rate	Baseline through Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pre-bronchodilator Forced expiratory volume in the first second (FEV1)		Baseline to week 12
Annualized cumulative dose of systemic corticosteroid exposure to treat severe asthma exacerbations		Baseline to week 52
Change in Asthma Control Questionnaire (ACQ-5)	The ACQ-5 has 5 items that assess the most common asthma symptoms: 1. Frequency in past week awoken by asthma during the night, 2. Severity of asthma symptoms in the morning, 3. Limitation of daily activities due to asthma, 4. Shortness of breath due to asthma and 5. Wheeze. Participants are asked to recall how their asthma has been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The ACQ-5 global score is the mean of the 5 questions and, therefore, between 0 (totally controlled) and 6 (severely uncontrolled). Higher score indicates lower asthma control.	Baseline to week 12
Proportion of participants achieving ACQ-5 <1.5		At week 12
Change in pre-bronchodilator FEV1		Baseline up to week 52
Change in percent predicted FEV1		Baseline up to week 52
Change in peak expiratory flow (PEF)		Baseline up to week 52
Change in forced vital capacity (FVC)		Baseline up to week 52
Change in forced expiratory flow (FEF) 25-75%		Baseline up to week 52
Change in FEV1: FVC ratio		Baseline up to week 52
Change in post-bronchodilator FEV1		Baseline up to week 52
Time to first severe exacerbation event		Up to week 52
Proportion of participants achieving a 0.5-point improvement minimal clinically important difference (MCID) in ACQ-5		Up to week 52
Incidence of Treatment-emergent adverse event (TEAEs)		Up to week 52

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2024
• Primary Completion (Estimated): April 24, 2027
• Study Completion (Estimated): April 24, 2027

Study Registration Dates

• First Submitted: August 23, 2024
• First Submitted That Met QC Criteria: August 23, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Uncontrolled; Severe exacerbations; Type 2 Inflammation; Elevated blood eosinophils; Increased Fractional exhaled Nitric Oxide (FeNO); Atopy and elevated Immunoglobulin E (IgE)
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; Organic Chemicals; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Fatty Acids, Volatile; Androstadienes; Androstenes; Androstanes; Fluticasone; dupilumab; Propionates
• Other Study ID Numbers: R668-AS-2373; 2023-510458-18-00 (Ctis: EU CT 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

When Regeneron has :

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• 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