Evaluation of Dupilumab in Children With Uncontrolled Asthma

NCT02948959 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC141532016-001607-23U1111-1179-4851
• Study Type: interventional
• Target: 408
• Locations: 18 countries
• Sites: 99

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (2)

• Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population

  A severe asthma exacerbation event was defined as a deterioration of asthma during the 52-week treatment period requiring: use of systemic corticosteroids for \>=3 days; and/or hospitalization or emergency room visit because of asthma requiring systemic corticosteroid treatment. Annualized event rate was defined as the total number of severe exacerbation events that occurred during the 52-week treatment period divided by the total number of participant-years followed in the 52-week treatment period.

  Baseline to Week 52

• Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population

  A severe asthma exacerbation event was defined as a deterioration of asthma during the 52-week treatment period requiring: use of systemic corticosteroids for \>=3 days; and/or hospitalization or emergency room visit because of asthma requiring systemic corticosteroid treatment. Annualized event rate was defined as the total number of severe exacerbation events that occurred during the 52-week treatment period divided by the total number of participant-years followed in the 52-week treatment period.

  Baseline to Week 52

Secondary Outcomes (48)

• Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 (FEV1) Second at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microliter Population

  Baseline, Week 12

• Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 12: Type 2 Inflammatory Asthma Phenotype Population

  Baseline, Week 12

• Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version (ACQ-7-IA) at Week 24: Baseline Blood Eosinophils >=300 Cells Per Microliter Population

  Baseline, Week 24

• Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Type 2 Inflammatory Asthma Phenotype Population

  Baseline, Week 24

• Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microliter Population

  Baseline, Week 12

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo; Drug: Asthma Controller Therapies; Drug: Asthma Reliever Therapies

Dupilumab

EXPERIMENTAL

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).

Drug: Dupilumab; Drug: Asthma Controller Therapies; Drug: Asthma Reliever Therapies

Interventions

Dupilumab DRUG

Pharmaceutical form: Solution Route of administration: Subcutaneous

Also known as: SAR231893 (REGN668)

Dupilumab

Placebo DRUG

Pharmaceutical form: Solution Route of administration: Subcutaneous

Placebo

Asthma Controller Therapies DRUG

Pharmaceutical form: Aerosol, capsules, tablets, oral solution Route of administration: Inhaled, oral

Dupilumab; Placebo

Asthma Reliever Therapies DRUG

Pharmaceutical form: Nebulized, aerosol Route of administration: Inhaled

Dupilumab; Placebo

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (99)

Investigational Site Number 840031

Birmingham, Alabama, 35209, United States

Location

Investigational Site Number 840002

Gilbert, Arizona, 85234, United States

Location

Investigational Site Number 840012

Tucson, Arizona, 85724-5030, United States

Location

Investigational Site Number 840001

Rolling Hills Estates, California, 90274, United States

Location

Investigational Site Number 840036

Owensboro, Kentucky, 42301, United States

Location

Investigational Site Number 840016

Ann Arbor, Michigan, 48106, United States

Location

Investigational Site Number 840006

St Louis, Missouri, 63110-1077, United States

Location

Investigational Site Number 840022

Lincoln, Nebraska, 68505, United States

Location

Investigational Site Number 840023

Great Neck, New York, 11021, United States

Location

Investigational Site Number 840035

New York, New York, 00000, United States

Location

Investigational Site Number 840013

New York, New York, 10032, United States

Location

Investigational Site Number 840007

Rochester, New York, 14607, United States

Location

Investigational Site Number 840004

Charlotte, North Carolina, 28277, United States

Location

Investigational Site Number 840021

Durham, North Carolina, 27710, United States

Location

Investigational Site Number 840008

Cincinnati, Ohio, 45229, United States

Location

Investigational Site Number 840024

Edmond, Oklahoma, 73034, United States

Location

Investigational Site Number 840003

San Antonio, Texas, 78229, United States

Location

Investigational Site Number 840018

La Crosse, Wisconsin, 54601, United States

Location

Investigational Site Number 032004

Buenos Aires, B1602DQD, Argentina

Location

Investigational Site Number 032003

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number 032002

Caba, C1122AAK, Argentina

Location

Investigational Site Number 032001

Caba, C1414AIF, Argentina

Location

Investigational Site Number 032006

Mendoza, 5500, Argentina

Location

Investigational Site Number 036001

Campbelltown, 2560, Australia

Location

Investigational Site Number 036005

North Adelaide, 5006, Australia

Location

Investigational Site Number 036003

Parkville/Melbourne, 3052, Australia

Location

Investigational Site Number 036002

South Brisbane, 4101, Australia

Location

Investigational Site Number 076008

Blumenau, 89030-100, Brazil

Location

Investigational Site Number 076001

Porto Alegre, 90020-090, Brazil

Location

Investigational Site Number 076007

Porto Alegre, 90610-000, Brazil

Location

Investigational Site Number 076003

São Paulo, 02189-010, Brazil

Location

Investigational Site Number 076002

São Paulo, 04037-002, Brazil

Location

Investigational Site Number 076004

São Paulo, 05403-000, Brazil

Location

Investigational Site Number 076006

Sorocaba, 18040-425, Brazil

Location

Investigational Site Number 124004

Edmonton, T6G 2B7, Canada

Location

Investigational Site Number 124002

Hamilton, L8S1G5, Canada

Location

Investigational Site Number 124001

Montreal, H3T 1C5, Canada

Location

Investigational Site Number 124003

Québec, G1V 4W2, Canada

Location

Investigational Site Number 152003

Santiago, 7560994, Chile

Location

Investigational Site Number 152005

Santiago, 838-0418, Chile

Location

Investigational Site Number 152009

Santiago, 8380453, Chile

Location

Investigational Site Number 152001

Valdivia, Chile

Location

Investigational Site Number 152007

Viña del Mar, 2520024, Chile

Location

Investigational Site Number 152002

Viña del Mar, 2520594, Chile

Location

Investigational Site Number 170004

Antioquia, 050010, Colombia

Location

Investigational Site Number 170002

Cali, 760043, Colombia

Location

Investigational Site Number 348006

Budapest, 1089, Hungary

Location

Investigational Site Number 348002

Gyula, 5700, Hungary

Location

Investigational Site Number 348012

Mezőkövesd, 3400, Hungary

Location

Investigational Site Number 348005

Szeged, 6720, Hungary

Location

Investigational Site Number 348001

Székesfehérvár, 8000, Hungary

Location

Investigational Site Number 348008

Szigetvár, 7900, Hungary

Location

Investigational Site Number 348003

Töröbálint, 2045, Hungary

Location

Investigational Site Number 348007

Zalaegerszeg, 8900, Hungary

Location

Investigational Site Number 380007

Catania, 95123, Italy

Location

Investigational Site Number 380003

Florence, 50139, Italy

Location

Investigational Site Number 380004

Padua, 35128, Italy

Location

Investigational Site Number 380005

Roma, 00146, Italy

Location

Investigational Site Number 380001

Verona, 37126, Italy

Location

Investigational Site Number 440002

Kaunas, LT-50161, Lithuania

Location

Investigational Site Number 440005

Šiauliai, LT-76231, Lithuania

Location

Investigational Site Number 440003

Utena, LT-28151, Lithuania

Location

Investigational Site Number 440001

Vilnius, LT-08406, Lithuania

Location

Investigational Site Number 440004

Vilnius, LT-09108, Lithuania

Location

Investigational Site Number 484006

Chihuahua City, 31000, Mexico

Location

Investigational Site Number 484004

Chihuahua City, 31200, Mexico

Location

Investigational Site Number 484003

Durango, 34080, Mexico

Location

Investigational Site Number 484001

Monterrey, 64460, Mexico

Location

Investigational Site Number 484002

Veracruz, 91910, Mexico

Location

Investigational Site Number 616001

Lodz, 90-329, Poland

Location

Investigational Site Number 616002

Poznan, 60-693, Poland

Location

Investigational Site Number 642001

Bucharest, 020395, Romania

Location

Investigational Site Number 643006

Moscow, 119333, Russia

Location

Investigational Site Number 643004

Perm, 614066, Russia

Location

Investigational Site Number 643005

Saint Petersburg, 191144, Russia

Location

Investigational Site Number 643002

Saint Petersburg, 193312, Russia

Location

Investigational Site Number 643001

Saint Petersburg, 194100, Russia

Location

Investigational Site Number 643003

Saint Petersburg, 196240, Russia

Location

Investigational Site Number 710004

Cape Town, 7500, South Africa

Location

Investigational Site Number 710001

Cape Town, 7700, South Africa

Location

Investigational Site Number 724001

Barcelona, 08035, Spain

Location

Investigational Site Number 724006

Esplugues de Llobregat, 08950, Spain

Location

Investigational Site Number 724005

Pozuelo de Alarcón, 28223, Spain

Location

Investigational Site Number 724002

Santiago de Compostela, 15706, Spain

Location

Investigational Site Number 724003

Valencia, 46017, Spain

Location

Investigational Site Number 792005

Adana, Turkey (Türkiye)

Location

Investigational Site Number 792008

Ankara, 06500, Turkey (Türkiye)

Location

Investigational Site Number 792001

Ankara, Turkey (Türkiye)

Location

Investigational Site Number 792006

Bursa, Turkey (Türkiye)

Location

Investigational Site Number 792003

Istanbul, Turkey (Türkiye)

Location

Investigational Site Number 792004

Istanbul, Turkey (Türkiye)

Location

Investigational Site Number 804007

Chernivtsi, 58023, Ukraine

Location

Investigational Site Number 804004

Dnipro, 49101, Ukraine

Location

Investigational Site Number 804011

Ivano-Frankivsk, 76014, Ukraine

Location

Investigational Site Number 804005

Kharkiv, 61093, Ukraine

Location

Investigational Site Number 804008

Kryvyi Rig, 50082, Ukraine

Location

Investigational Site Number 804001

Kyiv, 03115, Ukraine

Location

Investigational Site Number 804002

Zaporizhzhya, 69063, Ukraine

Location

Investigational Site Number 804003

Zaporizhzhya, 69076, Ukraine

Location

Related Publications (8)

• Jackson DJ, Hamelmann E, Roberts G, Bacharier LB, Xia C, Gall R, Ledanois O, Coleman A, Tawo K, Jacob-Nara JA, Radwan A, Rowe PJ, Deniz Y. Dupilumab Efficacy and Safety in Children With Moderate to Severe Asthma and High Blood Eosinophils: A Post Hoc Analysis of VOYAGE. J Allergy Clin Immunol Pract. 2025 Mar;13(3):568-575. doi: 10.1016/j.jaip.2024.11.014. Epub 2024 Nov 28.

  PMID: 39613097 DERIVED

• Guilbert TW, Murphy KR, Hamelmann E, Ross KR, Gupta A, Fiocchi A, Xia C, Gall R, Ledanois O, Radwan A, Jacob-Nara JA, Rowe PJ, Deniz Y. Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study. J Asthma Allergy. 2024 Feb 8;17:81-87. doi: 10.2147/JAA.S425101. eCollection 2024.

  PMID: 38347908 DERIVED

• Bacharier LB, Pavord ID, Maspero JF, Jackson DJ, Fiocchi AG, Mao X, Jacob-Nara JA, Deniz Y, Laws E, Mannent LP, Amin N, Akinlade B, Staudinger HW, Lederer DJ, Hardin M. Blood eosinophils and fractional exhaled nitric oxide are prognostic and predictive biomarkers in childhood asthma. J Allergy Clin Immunol. 2024 Jul;154(1):101-110. doi: 10.1016/j.jaci.2023.09.044. Epub 2024 Jan 23.

  PMID: 38272375 DERIVED

• Bacharier LB, Guilbert TW, Katelaris CH, Deschildre A, Phipatanakul W, Liu D, Altincatal A, Mannent LP, Amin N, Laws E, Akinlade B, Jacob-Nara JA, Deniz Y, Rowe PJ, Lederer DJ, Hardin M. Dupilumab Improves Lung Function Parameters in Pediatric Type 2 Asthma: VOYAGE Study. J Allergy Clin Immunol Pract. 2024 Apr;12(4):948-959. doi: 10.1016/j.jaip.2023.12.006. Epub 2023 Dec 11.

  PMID: 38092225 DERIVED

• Fiocchi AG, Phipatanakul W, Zeiger RS, Durrani SR, Cole J, Msihid J, Gall R, Jacob-Nara JA, Deniz Y, Rowe PJ, Lederer DJ, Hardin M, Zhang Y, Khan AH. Dupilumab leads to better-controlled asthma and quality of life in children: the VOYAGE study. Eur Respir J. 2023 Nov 2;62(5):2300558. doi: 10.1183/13993003.00558-2023. Print 2023 Nov.

  PMID: 37734856 DERIVED

• Papadopoulos NG, Szefler SJ, Bacharier LB, Maspero JF, Domingo C, Fiocchi A, Lee JK, Daizadeh N, Lederer DJ, Hardin M, Gall R, Djandji M, Siddiqui S, Jacob-Nara JA, Deniz Y, Rowe PJ. Assessment of dupilumab in children with moderate-to-severe type 2 asthma with or without evidence of allergic asthma. Allergy. 2023 Aug;78(8):2157-2167. doi: 10.1111/all.15743. Epub 2023 May 25.

  PMID: 37059696 DERIVED

• 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.

  PMID: 36958470 DERIVED

• Bacharier LB, Maspero JF, Katelaris CH, Fiocchi AG, Gagnon R, de Mir I, Jain N, Sher LD, Mao X, Liu D, Zhang Y, Khan AH, Kapoor U, Khokhar FA, Rowe PJ, Deniz Y, Ruddy M, Laws E, Patel N, Weinreich DM, Yancopoulos GD, Amin N, Mannent LP, Lederer DJ, Hardin M; Liberty Asthma VOYAGE Investigators. Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma. N Engl J Med. 2021 Dec 9;385(24):2230-2240. doi: 10.1056/NEJMoa2106567.

  PMID: 34879449 DERIVED

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

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: October 27, 2016
• First Posted: October 31, 2016
• Study Start: April 21, 2017
• Primary Completion: August 26, 2020
• Study Completion: August 26, 2020
• Last Updated: March 28, 2022
• Results First Posted: October 20, 2021

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

CO (2); ME (5); ZA (2); HU (8); AU (4); IT (5); RO (1); BR (7); CL (6); ES (5); CA (4); RU (6); UA (8); AR (5); TU (6); LI (5); PL (2); US (18)