Clinical trial NCT02948959: Evaluation of Dupilumab in Children With Uncontrolled Asthma
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Children 6 to <12 Years of Age With Uncontrolled Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2016-10-31
Enrollment: 408
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline to Week 52
measure: Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: 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
timeFrame: Baseline, Week 12
measure: Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 12: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Week 12
measure: 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
timeFrame: Baseline, Week 24
measure: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Week 12
measure: Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Week 12
measure: Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 24, 36 and 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 24, 36, 52
measure: Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 24, 36 and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 24, 36, 52
measure: Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline up to Week 52
measure: Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline up to Week 52
measure: Time to First Loss of Asthma Control (LOAC) Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline up to Week 52
measure: Time to First Loss of Asthma Control Event: Kaplan-Meier Estimates During 52-week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline up to Week 52
measure: Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Percent Change From Baseline in Pre-Bronchodilator Percent Predicted FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Percent Change From Baseline in Pre-Bronchodilator Percent Predicted FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Morning (AM) Peak Expiratory Flow (PEF) at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Evening (PM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Morning (AM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Evening (PM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Forced Vital Capacity at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Forced Expiratory Flow 25-75% at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-question Version (ACQ-5-IA) at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-question Version at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Weeks 2, 4, 8, 12, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8,12, 36, 52
measure: Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Weeks 2, 4, 8, 12, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8,12, 36, 52
measure: Change From Baseline in Number of Puffs of Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Number of Puffs of Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
measure: Change From Baseline in Pediatric Asthma Quality of Life (QoL) Questionnaire With Standardized Activities-Interviewer Administered (PAQLQ[S] IA) Scores at Weeks 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline, Weeks 12, 24, 36, 52
measure: Change From Baseline in Pediatric Asthma Quality of Life Questionnaire With Standardized Activities-Interviewer Administered Scores at Weeks 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline, Weeks 12, 24, 36, 52
measure: Healthcare Resource Utilization (HCRU): Number of School and Work Days Missed Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline to Week 52
measure: Healthcare Resource Utilization: Number of School and Work Days Missed Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline to Week 52
measure: Healthcare Resource Utilization: Percentage of Participants Who Had Missed Greater Than or Equal to 5 School/Work Days Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population
timeFrame: Baseline to Week 52
measure: Healthcare Resource Utilization: Percentage of Participants Who Had Missed Greater Than or Equal to 5 School/Work Days Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microliter Population
timeFrame: Baseline to Week 52
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From Baseline up to Week 64
measure: Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum
timeFrame: Baseline, Weeks 6, 12, 24, 52, 64
measure: Percentage of Participants With Treatment Emergent Antidrug Antibodies (ADA) Response
timeFrame: From Baseline up to Week 64
measure: Percentage of Participants With Seroconversion
timeFrame: From Baseline up to Week 64
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 840031
state: Alabama
city: Gilbert
country: United States
facility: Investigational Site Number 840002
state: Arizona
city: Tucson
country: United States
facility: Investigational Site Number 840012
state: Arizona
city: Rolling Hills Estates
country: United States
facility: Investigational Site Number 840001
state: California
city: Owensboro
country: United States
facility: Investigational Site Number 840036
state: Kentucky
city: Ann Arbor
country: United States
facility: Investigational Site Number 840016
state: Michigan
city: Saint Louis
country: United States
facility: Investigational Site Number 840006
state: Missouri
city: Lincoln
country: United States
facility: Investigational Site Number 840022
state: Nebraska
city: Great Neck
country: United States
facility: Investigational Site Number 840023
state: New York
city: New York
country: United States
facility: Investigational Site Number 840035
state: New York
city: New York
country: United States
facility: Investigational Site Number 840013
state: New York
city: Rochester
country: United States
facility: Investigational Site Number 840007
state: New York
city: Charlotte
country: United States
facility: Investigational Site Number 840004
state: North Carolina
city: Durham
country: United States
facility: Investigational Site Number 840021
state: North Carolina
city: Cincinnati
country: United States
facility: Investigational Site Number 840008
state: Ohio
city: Edmond
country: United States
facility: Investigational Site Number 840024
state: Oklahoma
city: San Antonio
country: United States
facility: Investigational Site Number 840003
state: Texas
city: La Crosse
country: United States
facility: Investigational Site Number 840018
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 032004
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 032003
city: Caba
country: Argentina
facility: Investigational Site Number 032002
city: Caba
country: Argentina
facility: Investigational Site Number 032001
city: Mendoza
country: Argentina
facility: Investigational Site Number 032006
city: Campbelltown
country: Australia
facility: Investigational Site Number 036001
city: North Adelaide
country: Australia
facility: Investigational Site Number 036005
city: Parkville/Melbourne
country: Australia
facility: Investigational Site Number 036003
city: South Brisbane
country: Australia
facility: Investigational Site Number 036002
city: Blumenau
country: Brazil
facility: Investigational Site Number 076008
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 076001
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 076007
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076003
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076002
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076004
city: Sorocaba
country: Brazil
facility: Investigational Site Number 076006
city: Edmonton
country: Canada
facility: Investigational Site Number 124004
city: Hamilton
country: Canada
facility: Investigational Site Number 124002
city: Montreal
country: Canada
facility: Investigational Site Number 124001
city: Quebec
country: Canada
facility: Investigational Site Number 124003
city: Santiago
country: Chile
facility: Investigational Site Number 152003
city: Santiago
country: Chile
facility: Investigational Site Number 152005
city: Santiago
country: Chile
facility: Investigational Site Number 152009
city: Valdivia
country: Chile
facility: Investigational Site Number 152001
city: Viña Del Mar
country: Chile
facility: Investigational Site Number 152007
city: Viña Del Mar
country: Chile
facility: Investigational Site Number 152002
city: Antioquia
country: Colombia
facility: Investigational Site Number 170004
city: Cali
country: Colombia
facility: Investigational Site Number 170002
city: Budapest
country: Hungary
facility: Investigational Site Number 348006
city: Gyula
country: Hungary
facility: Investigational Site Number 348002
city: Mezőkövesd
country: Hungary
facility: Investigational Site Number 348012
city: Szeged
country: Hungary
facility: Investigational Site Number 348005
city: Szigetvár
country: Hungary
facility: Investigational Site Number 348008
city: Székesfehérvár
country: Hungary
facility: Investigational Site Number 348001
city: Töröbálint
country: Hungary
facility: Investigational Site Number 348003
city: Zalaegerszeg
country: Hungary
facility: Investigational Site Number 348007
city: Catania
country: Italy
facility: Investigational Site Number 380007
city: Firenze
country: Italy
facility: Investigational Site Number 380003
city: Padova
country: Italy
facility: Investigational Site Number 380004
city: Roma
country: Italy
facility: Investigational Site Number 380005
city: Verona
country: Italy
facility: Investigational Site Number 380001
city: Kaunas
country: Lithuania
facility: Investigational Site Number 440002
city: Siauliai
country: Lithuania
facility: Investigational Site Number 440005
city: Utena
country: Lithuania
facility: Investigational Site Number 440003
city: Vilnius
country: Lithuania
facility: Investigational Site Number 440001
city: Vilnius
country: Lithuania
facility: Investigational Site Number 440004
city: Chihuahua
country: Mexico
facility: Investigational Site Number 484006
city: Chihuahua
country: Mexico
facility: Investigational Site Number 484004
city: Durango
country: Mexico
facility: Investigational Site Number 484003
city: Monterrey
country: Mexico
facility: Investigational Site Number 484001
city: Veracruz
country: Mexico
facility: Investigational Site Number 484002
city: Lodz
country: Poland
facility: Investigational Site Number 616001
city: Poznan
country: Poland
facility: Investigational Site Number 616002
city: Bucuresti
country: Romania
facility: Investigational Site Number 642001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643006
city: Perm
country: Russian Federation
facility: Investigational Site Number 643004
city: Saint Petersburg
country: Russian Federation
facility: Investigational Site Number 643005
city: Saint Petersburg
country: Russian Federation
facility: Investigational Site Number 643002
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 643001
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 643003
city: Cape Town
country: South Africa
facility: Investigational Site Number 710004
city: Cape Town
country: South Africa
facility: Investigational Site Number 710001
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
city: Esplugues De Llobregat
country: Spain
facility: Investigational Site Number 724006
city: Pozuelo De Alarcón
country: Spain
facility: Investigational Site Number 724005
city: Santiago De Compostela
country: Spain
facility: Investigational Site Number 724002
city: Valencia
country: Spain
facility: Investigational Site Number 724003
city: Adana
country: Turkey
facility: Investigational Site Number 792005
city: Ankara
country: Turkey
facility: Investigational Site Number 792008
city: Ankara
country: Turkey
facility: Investigational Site Number 792001
city: Bursa
country: Turkey
facility: Investigational Site Number 792006
city: İstanbul
country: Turkey
facility: Investigational Site Number 792003
city: Istanbul
country: Turkey
facility: Investigational Site Number 792004
city: Chernivtsi
country: Ukraine
facility: Investigational Site Number 804007
city: Dnipro
country: Ukraine
facility: Investigational Site Number 804004
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number 804011
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 804005
city: Kryvyi Rig
country: Ukraine
facility: Investigational Site Number 804008
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804001
city: Zaporizhzhya
country: Ukraine
facility: Investigational Site Number 804002
city: Zaporizhzhya
country: Ukraine
facility: Investigational Site Number 804003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.