Clinical trial NCT06572228: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Asthma
Keywords: Uncontrolled
Severe exacerbations
Type 2 Inflammation
Elevated blood eosinophils
Increased Fractional exhaled Nitric Oxide (FeNO)
Atopy and elevated Immunoglobulin E (IgE)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2024-08-27
Enrollment: 250
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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

Eligibility criteria: 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

Primary outcomes:
measure: Annualized severe asthma exacerbation rate
timeFrame: Baseline through Week 52
Secondary outcomes:
measure: Change in pre-bronchodilator Forced expiratory volume in the first second (FEV1)
timeFrame: Baseline to week 12
measure: Annualized cumulative dose of systemic corticosteroid exposure to treat severe asthma exacerbations
timeFrame: Baseline to week 52
measure: Change in Asthma Control Questionnaire (ACQ-5)
timeFrame: Baseline to week 12
measure: Proportion of participants achieving ACQ-5 <1.5
timeFrame: At week 12
measure: Change in pre-bronchodilator FEV1
timeFrame: Baseline up to week 52
measure: Change in percent predicted FEV1
timeFrame: Baseline up to week 52
measure: Change in peak expiratory flow (PEF)
timeFrame: Baseline up to week 52
measure: Change in forced vital capacity (FVC)
timeFrame: Baseline up to week 52
measure: Change in forced expiratory flow (FEF) 25-75%
timeFrame: Baseline up to week 52
measure: Change in FEV1: FVC ratio
timeFrame: Baseline up to week 52
measure: Change in post-bronchodilator FEV1
timeFrame: Baseline up to week 52
measure: Time to first severe exacerbation event
timeFrame: Up to week 52
measure: Proportion of participants achieving a 0.5-point improvement minimal clinically important difference (MCID) in ACQ-5
timeFrame: Up to week 52
measure: Incidence of Treatment-emergent adverse event (TEAEs)
timeFrame: Up to week 52
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Kern Research, Inc
state: California
city: La Jolla
country: United States
facility: Modena Allergy & Asthma, Inc.
state: California
city: Lancaster
country: United States
facility: Antelope Valley Clinical Trials
state: California
city: Long Beach
country: United States
facility: Ark Clinical Research - Long Beach
state: California
city: Newport Beach
country: United States
facility: Newport Native Md, Inc.
state: California
city: Redondo Beach
country: United States
facility: Riviera Allergy Medical Center
state: California
city: Santa Monica
country: United States
facility: Raffi Tachdjian MD inc
state: California
city: Stockton
country: United States
facility: Bensch Clinical Research
state: California
city: Upland
country: United States
facility: Integrated Research of Inland, Inc.
state: California
city: Westminster
country: United States
facility: Allianz Research Institute
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Clearwater
country: United States
facility: St Francis Medical Institute
state: Florida
city: Kissimmee
country: United States
facility: Florida Lung, Asthma and Sleep Specialists (FLASS) - Celebration
state: Florida
city: Winter Park
country: United States
facility: Clinical Site Partners, LLC DBA Flourish Research
state: Florida
city: Boise
country: United States
facility: Treasure Valley Medical Research
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Normal
country: United States
facility: Sneeze Wheeze and Itch Associates
state: Illinois
city: River Forest
country: United States
facility: Asthma and Allergy Center of Chicago
state: Illinois
city: Skokie
country: United States
facility: NorthShore University Health System
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Bluegrass Allergy Research
state: Kentucky
city: Louisville
country: United States
facility: Family Allergy and Asthma Research Institute
state: Kentucky
city: Owensboro
country: United States
facility: Allergy & Asthma Specialists, P.S.C.
state: Kentucky
city: Bangor
country: United States
facility: Paul A. Shapero, M.D.
state: Maine
city: Dover
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Maplewood
country: United States
facility: Allergy and Asthma Center of Minnesota
state: Minnesota
city: Minneapolis
country: United States
facility: Clinical Research Institute, Inc.
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Missoula
country: United States
facility: Montana Medical Research
state: Montana
city: Bellevue
country: United States
facility: The Asthma and Allergy Center
state: Nebraska
city: Henderson
country: United States
facility: Henderson Clinical Trials
state: Nevada
city: Cortland
country: United States
facility: Certified Research Associates
state: New York
city: Hawthorne
country: United States
facility: New York Medical College
state: New York
city: Rochester
country: United States
facility: Rochester Regional Health - Alexander Park - Allergy, Immunology & Rheumatology
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital and Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Allergy, Asthma and Clinical Research Center
state: Oklahoma
city: DuBois
country: United States
facility: Clinical Research Associates of Central PA
state: Pennsylvania
city: Wynnewood
country: United States
facility: Pulmonology Associates Inc.
state: Pennsylvania
city: Dallas
country: United States
facility: Dharma MD PA doing business as Southwest Family Medicine Associates
state: Texas
city: Denison
country: United States
facility: Premier Pulmonary Critical Care and Sleep Medicine
state: Texas
city: El Paso
country: United States
facility: Western Sky Medical Research
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Section of Pulmonary and Critical Care
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: McKinney
country: United States
facility: Metroplex Pulmonary and Sleep Center, PA
state: Texas
city: North Richland Hills
country: United States
facility: Lung Sleep Research Institute
state: Texas
city: San Antonio
country: United States
facility: South Texas Allegry & Asthma Medical Professionals (STAAMP) Research
state: Texas
city: Waco
country: United States
facility: Allergy & Asthma Care of Waco
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Vancouver
country: United States
facility: Vancouver Clinic
state: Washington
city: Vancouver
country: Canada
facility: The Lung Centre at Vancouver General Hospital
state: British Columbia
city: Ajax
country: Canada
facility: Dynamic Drug Advancement Ltd.
state: Ontario
city: Toronto
country: Canada
facility: Evidence Based Medical Educator Inc.
state: Ontario
city: Toronto
country: Canada
facility: Inspiration Research Limited
state: Ontario
city: Windsor
country: Canada
facility: Dr. Syed Anees Medicine Professional Corporation
state: Ontario
city: Quebec
country: Canada
facility: Clinique de Specialisee en Allergie de la Capitale
city: Vejle
country: Denmark
facility: Vejle Sygehus
state: South Denmark
city: Hvidovre
country: Denmark
facility: Copenhagen University Hospital - Hvidovre
city: Munich
country: Germany
facility: Lmu University Hospital
state: Bavaria
city: Augsburg
country: Germany
facility: Praxis fur Pneumologie am Duako
state: Bayern
city: Frankfurt
country: Germany
facility: IKF Pneumologie Frankfurt GmbH & Co KG
state: Hessen
city: Koblenz
country: Germany
facility: KPPK Studienzentrum
state: Rheinland-Pfalz
city: Lubeck
country: Germany
facility: Velocity Clinical Research Lubeck GmbH (Formerly KLB Gesundheitsforschung Lübeck GmbH)
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Lungenpraxis Hohenzollerndamm RCMS
city: Leipzig
country: Germany
facility: POIS Sachsen GmbH iG
city: Mainz
country: Germany
facility: IKF Pneumologie GmbH & Co. KG
city: Wroclaw
country: Poland
facility: Michał Bogacki - DOBROSTAN
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Diamond Clinic sp zoo
state: Malopolska
city: Cracow
country: Poland
facility: Centrum Medyczne All-Med
state: Malopolskie
city: Białystok
country: Poland
facility: Centrum Medycyny Oddechowej Mroz SJ
state: Podlaskie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Budynek Centrum Medycyny Nieinwazyjnej
state: Pomerania
city: Bialystok
country: Poland
facility: Allergy Clinic NZOZ Homeo Medicus
city: Wroclaw
country: Poland
facility: Lekarze Specjaliści Małolepszy i Partnerzy
city: Wroclaw
country: Poland
facility: ALL-MED Specjalistyczna Opieka Medyczna Medyczny Instytut Badawczy
city: Guaynabo
country: Puerto Rico
facility: Allianze pulmonary Research
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigacion (FDI) Clinical Research
city: San Juan
country: Puerto Rico
facility: PRCCI Clinical Research Center
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: