Evaluation of Dupilumab in Children With Uncontrolled Asthma

NCT ID: NCT02948959

Last Updated: 2022-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 408 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-21
• Study Completion Date: 2020-08-26

Brief Summary

Primary Objective:

To evaluate the efficacy of dupilumab in children 6 to less than (<) 12 years of age with uncontrolled persistent asthma.

Secondary Objective:

To evaluate in children 6 to <12 years of age with uncontrolled persistent asthma:

• The safety and tolerability of dupilumab.
• The evaluate the effect of dupilumab in improving participant reported outcomes including health related quality of life.
• The dupilumab systemic exposure and incidence of anti-drug antibodies.
• The evaluate the association between dupilumab treatment and pediatric immune responses to vaccines: any vaccination for tetanus, diphtheria, pertussis and/or seasonal trivalent/quadrivalent influenza vaccine.

Detailed Description

The total study duration per participant was up to 69 weeks, consisted of a screening period of 3-5 weeks, a randomized treatment period of 52 weeks and a post-treatment period of 12 weeks.

Conditions

Asthma

Study Design

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

Study Groups

Placebo

Placebo (for Dupilumab), subcutaneous (SC) injection every 2 weeks (q2w) for 52 weeks in combination with stable-dose background therapy of medium-dose inhaled corticosteroids (ICS) with a second controller medication (i.e., long-acting β2 agonist \[LABA\], long acting muscarinic antagonist \[LAMA\], leukotriene receptor antagonist \[LTRA\] or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Participants were followed up for 12 weeks after last dose (i.e. up to Week 64).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Asthma Controller Therapies

Intervention Type: DRUG

Pharmaceutical form: Aerosol, capsules, tablets, oral solution

Route of administration: Inhaled, oral

Asthma Reliever Therapies

Intervention Type: DRUG

Pharmaceutical form: Nebulized, aerosol

Route of administration: Inhaled

Dupilumab

Dupilumab 200 milligrams (mg) (in 1.14 milliliters \[mL\] for \>30 kilograms \[kg\] bodyweight \[BW\]) or 100 mg (in 0.67 mL for less than or equal to (\<=) 30 kg BW), SC injection q2w for 52 weeks in combination with stable-dose background therapy of medium-dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA\] or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Participants were followed up for 12 weeks after last dose (i.e. up to Week 64).

Group Type: EXPERIMENTAL

Dupilumab

Intervention Type: DRUG

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Asthma Controller Therapies

Intervention Type: DRUG

Pharmaceutical form: Aerosol, capsules, tablets, oral solution

Route of administration: Inhaled, oral

Asthma Reliever Therapies

Intervention Type: DRUG

Pharmaceutical form: Nebulized, aerosol

Route of administration: Inhaled

Interventions

Dupilumab

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Intervention Type: DRUG

Placebo

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Intervention Type: DRUG

Asthma Controller Therapies

Pharmaceutical form: Aerosol, capsules, tablets, oral solution

Route of administration: Inhaled, oral

Intervention Type: DRUG

Asthma Reliever Therapies

Pharmaceutical form: Nebulized, aerosol

Route of administration: Inhaled

Intervention Type: DRUG

Other Intervention Names

SAR231893 (REGN668)

Eligibility Criteria

Inclusion Criteria

Children 6 to <12 years of age, with a physician diagnosis of persistent asthma for greater than or equal to (>=)12 months prior to screening, based on clinical history and examination, pulmonary function parameters according to Global initiative for asthma (GINA) 2015 Guidelines and the following criteria:

• Existing background therapy of medium-dose ICS with second controller medication (i.e., long-acting β2 agonist , leukotriene receptor antagonist, long acting muscarinic antagonist, or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller, for at least 3 months with a stable dose >=1 month prior to Screening Visit 1.
• Pre-bronchodilator forced expiratory volume in 1 second (FEV1) <=95 percentage (%) of predicted normal or pre bronchodilator FEV1/forced vital capacity ratio <0.85 at Screening and Baseline Visits.
• Reversibility of at least 10% in FEV1 after the administration of 200 to 400 micrograms (mcg; 2 to 4 puff inhalations with metered-dose inhaler [MDI]) of albuterol/salbutamol or 45 to 90 mcg (2 to 4 puffs with MDI) of levalbuterol/levosalbutamol reliever medication before randomization (up to 3 opportunities during the same visit were allowed with a maximum of 12 puffs of reliever medication if tolerated by the participant).
• Must had experienced, within 1 year prior to Screening Visit 1, any of the following events:

• Treatment with a systemic corticosteroid (oral or parenteral), as prescribed by a healthcare professional for worsening asthma at least once or,
• Hospitalization or emergency visit for worsening asthma.
• Evidence of uncontrolled asthma, with at least one of the following criteria during the 4 (±1) weeks Screening Period:

• Asthma Control Questionnaire-Interviewer Administered (ACQ-IA) ACQ-5 score >=1.5 on at least one day of the Screening Period.
• Use of reliever medication (i.e., albuterol/salbutamol or levalbuterol/levosalbutamol), other than as a preventive for exercise induced bronchospasm, on 3 or more days per week, in at least one week during the Screening Period.
• Sleep awakening due to asthma symptoms requiring use of reliever medication at least once during the Screening Period.
• Asthma symptoms 3 or more days per week in at least one week during the Screening Period.

Exclusion Criteria

• Participants <6 or >=12 years of age.
• Participants with <16 kg bodyweight.
• Any other chronic lung disease (cystic fibrosis, bronchopulmonary dysplasia, etc.), which may impair lung function.
• A participant with any history of life threatening asthma (ie, extreme exacerbation that requires intubation).
• Co-morbid disease that might interfere with the evaluation of investigational medicinal product.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 11 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

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840031

Birmingham, Alabama, United States

Investigational Site Number 840002

Gilbert, Arizona, United States

Investigational Site Number 840012

Tucson, Arizona, United States

Investigational Site Number 840001

Rolling Hills Estates, California, United States

Investigational Site Number 840036

Owensboro, Kentucky, United States

Investigational Site Number 840016

Ann Arbor, Michigan, United States

Investigational Site Number 840006

St Louis, Missouri, United States

Investigational Site Number 840022

Lincoln, Nebraska, United States

Investigational Site Number 840023

Great Neck, New York, United States

Investigational Site Number 840035

New York, New York, United States

Investigational Site Number 840013

New York, New York, United States

Investigational Site Number 840007

Rochester, New York, United States

Investigational Site Number 840004

Charlotte, North Carolina, United States

Investigational Site Number 840021

Durham, North Carolina, United States

Investigational Site Number 840008

Cincinnati, Ohio, United States

Investigational Site Number 840024

Edmond, Oklahoma, United States

Investigational Site Number 840003

San Antonio, Texas, United States

Investigational Site Number 840018

La Crosse, Wisconsin, United States

Investigational Site Number 032004

Buenos Aires, , Argentina

Investigational Site Number 032003

Buenos Aires, , Argentina

Investigational Site Number 032002

Caba, , Argentina

Investigational Site Number 032001

Caba, , Argentina

Investigational Site Number 032006

Mendoza, , Argentina

Investigational Site Number 036001

Campbelltown, , Australia

Investigational Site Number 036005

North Adelaide, , Australia

Investigational Site Number 036003

Parkville/Melbourne, , Australia

Investigational Site Number 036002

South Brisbane, , Australia

Investigational Site Number 076008

Blumenau, , Brazil

Investigational Site Number 076001

Porto Alegre, , Brazil

Investigational Site Number 076007

Porto Alegre, , Brazil

Investigational Site Number 076003

São Paulo, , Brazil

Investigational Site Number 076002

São Paulo, , Brazil

Investigational Site Number 076004

São Paulo, , Brazil

Investigational Site Number 076006

Sorocaba, , Brazil

Investigational Site Number 124004

Edmonton, , Canada

Investigational Site Number 124002

Hamilton, , Canada

Investigational Site Number 124001

Montreal, , Canada

Investigational Site Number 124003

Québec, , Canada

Investigational Site Number 152003

Santiago, , Chile

Investigational Site Number 152005

Santiago, , Chile

Investigational Site Number 152009

Santiago, , Chile

Investigational Site Number 152001

Valdivia, , Chile

Investigational Site Number 152007

Viña del Mar, , Chile

Investigational Site Number 152002

Viña del Mar, , Chile

Investigational Site Number 170004

Antioquia, , Colombia

Investigational Site Number 170002

Cali, , Colombia

Investigational Site Number 348006

Budapest, , Hungary

Investigational Site Number 348002

Gyula, , Hungary

Investigational Site Number 348012

Mezőkövesd, , Hungary

Investigational Site Number 348005

Szeged, , Hungary

Investigational Site Number 348001

Székesfehérvár, , Hungary

Investigational Site Number 348008

Szigetvár, , Hungary

Investigational Site Number 348003

Töröbálint, , Hungary

Investigational Site Number 348007

Zalaegerszeg, , Hungary

Investigational Site Number 380007

Catania, , Italy

Investigational Site Number 380003

Florence, , Italy

Investigational Site Number 380004

Padua, , Italy

Investigational Site Number 380005

Roma, , Italy

Investigational Site Number 380001

Verona, , Italy

Investigational Site Number 440002

Kaunas, , Lithuania

Investigational Site Number 440005

Šiauliai, , Lithuania

Investigational Site Number 440003

Utena, , Lithuania

Investigational Site Number 440001

Vilnius, , Lithuania

Investigational Site Number 440004

Vilnius, , Lithuania

Investigational Site Number 484006

Chihuahua City, , Mexico

Investigational Site Number 484004

Chihuahua City, , Mexico

Investigational Site Number 484003

Durango, , Mexico

Investigational Site Number 484001

Monterrey, , Mexico

Investigational Site Number 484002

Veracruz, , Mexico

Investigational Site Number 616001

Lodz, , Poland

Investigational Site Number 616002

Poznan, , Poland

Investigational Site Number 642001

Bucharest, , Romania

Investigational Site Number 643006

Moscow, , Russia

Investigational Site Number 643004

Perm, , Russia

Investigational Site Number 643005

Saint Petersburg, , Russia

Investigational Site Number 643002

Saint Petersburg, , Russia

Investigational Site Number 643001

Saint Petersburg, , Russia

Investigational Site Number 643003

Saint Petersburg, , Russia

Investigational Site Number 710004

Cape Town, , South Africa

Investigational Site Number 710001

Cape Town, , South Africa

Investigational Site Number 724001

Barcelona, , Spain

Investigational Site Number 724006

Esplugues de Llobregat, , Spain

Investigational Site Number 724005

Pozuelo de Alarcón, , Spain

Investigational Site Number 724002

Santiago de Compostela, , Spain

Investigational Site Number 724003

Valencia, , Spain

Investigational Site Number 792005

Adana, , Turkey (Türkiye)

Investigational Site Number 792008

Ankara, , Turkey (Türkiye)

Investigational Site Number 792001

Ankara, , Turkey (Türkiye)

Investigational Site Number 792006

Bursa, , Turkey (Türkiye)

Investigational Site Number 792003

Istanbul, , Turkey (Türkiye)

Investigational Site Number 792004

Istanbul, , Turkey (Türkiye)

Investigational Site Number 804007

Chernivtsi, , Ukraine

Investigational Site Number 804004

Dnipro, , Ukraine

Investigational Site Number 804011

Ivano-Frankivsk, , Ukraine

Investigational Site Number 804005

Kharkiv, , Ukraine

Investigational Site Number 804008

Kryvyi Rig, , Ukraine

Investigational Site Number 804001

Kyiv, , Ukraine

Investigational Site Number 804002

Zaporizhzhya, , Ukraine

Investigational Site Number 804003

Zaporizhzhya, , Ukraine

Countries

United States; Argentina; Australia; Brazil; Canada; Chile; Colombia; Hungary; Italy; Lithuania; Mexico; Poland; Romania; Russia; South Africa; Spain; Turkey (Türkiye); Ukraine

References

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Jackson DJ, Bacharier LB, Phipatanakul W, Sher L, Domingo C, Papadopoulos N, Modena B, Li N, Xia C, Kamal MA, Dillon M, Wolfe K, Gall R, Amin N, Mannent LP, Laws E, Rowe PJ, Jacob-Nara JA, Deniz Y, Lederer DJ, Hardin M, Xu C. Dupilumab pharmacokinetics and effect on type 2 biomarkers in children with moderate-to-severe asthma. Ann Allergy Asthma Immunol. 2023 Jul;131(1):44-51.e4. doi: 10.1016/j.anai.2023.03.014. Epub 2023 Mar 22.

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001607-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1179-4851

Identifier Type: OTHER

Identifier Source: secondary_id

EFC14153

Identifier Type: -

Identifier Source: org_study_id