Study to Assess the Long-term Safety of Dupilumab Administered in Participants ≥6 Months to <18 Years of Age With Atopic Dermatitis (AD)

An Open-Label Extension Study to Assess the Long-Term Safety and Efficacy of Dupilumab in Patients ≥6 Months to <18 Years of Age With Atopic Dermatitis

The primary objective of the study is to assess the long-term safety of dupilumab in pediatric participants with AD.

The secondary objectives of the study are:

• To assess the long-term efficacy of dupilumab in pediatric participants with AD
• To assess the trough concentrations of functional dupilumab in serum and the immunogenicity in pediatric participants with AD after re-treatment with dupilumab

Optional Pre-filled Pen (PFP) Sub-Study in pediatric patients ≥2 to <12 years of age with AD

Co-Primary Objectives are:

• To evaluate the pharmacokinetic (PK) of dupilumab PFPs
• To evaluate the safety of dupilumab PFPs

Secondary Objective is:

- To evaluate the immunogenicity of dupilumab PFPs

Study Overview

• Status: Active, not recruiting
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Dupilumab

• Study Type: Interventional
• Enrollment (Actual): 880
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2G 1B1
      • Regeneron Investigational Site
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 6A7
      • Regeneron Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 0N2
      • Regeneron Investigational Site
  • Ontario
    • Markham, Ontario, Canada, L3P 1X2
      • Regeneron Investigational Site
    • Ottawa, Ontario, Canada, K2C 2N3
      • Regeneron Investigational Site
    • Peterborough, Ontario, Canada, K9J 5K2
      • Regeneron Investigational Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • Regeneron Investigational Site
    • Windsor, Ontario, Canada, N8W 1E6
      • Regeneron Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Regeneron Investigational Site
• Czechia
  • Kutna Hora, Czechia, 28401
    • Regeneron Investigational Site
  • Prague, Czechia, 10034
    • Regeneron Investigational Site
  • Ústí Nad Labem, Czechia, 40113
    • Regeneron Investigational Site
• Germany
  • Gera, Germany, 07548
    • Regeneron Investigational Site
  • Hamburg, Germany, 22149
    • Regeneron Investigational Site
  • Muenchen, Germany, 80802
    • Regeneron Study Site
  • Munich, Germany, 80337
    • Regeneron Investigational Site
  • Baden-Wuerttemberg
    • Tuebingen, Baden-Wuerttemberg, Germany, 72076
      • Regeneron Study Site
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • Regeneron Investigational Site
  • North Rhine-Westphal
    • Muenster, North Rhine-Westphal, Germany, 48149
      • Regeneron Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Regeneron Investigational Site
• Hungary
  • Kaposvar, Hungary, 7400
    • Regeneron Investigational Site
  • Miskolc, Hungary, 3526
    • Regeneron Investigational Site
  • Szeged, Hungary, 6720
    • Regeneron Investigational Site
  • Jasz-Nagykun-Szolnok
    • Szolnok, Jasz-Nagykun-Szolnok, Hungary, 5000
      • Regeneron Investigational Site
• Poland
  • Białystok, Poland, 15 453
    • Regeneron Investigational Site
  • Bydgoszcz, Poland, 85-065
    • Regeneron Investigational Site
  • Chorzow, Poland, 41-500
    • Regeneron Investigational Site
  • Gdańsk, Poland, 80-152
    • Regeneron Investigational Site
  • Katowice, Poland, 40 611
    • Regeneron Investigational Site
  • Kraków, Poland, 30 363
    • Regeneron Investigational Site
  • Lodz, Poland, 90-265
    • Regeneron Investigational Site
  • Warszawa, Poland, 01-142
    • Regeneron Investigational Site
  • Warszawa, Poland, 01-817
    • Regeneron Investigational Site
  • Warszawa, Poland, 02-758
    • Regeneron Investigational Site
  • Warszawa, Poland, 91-142
    • Regeneron Investigational Site
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50368
      • Regeneron Investigational Site
    • Wrocław, Dolnoslaskie, Poland, 50-381
      • Regeneron Investigational Site
  • Kielce
    • Ostrowiec Świętokrzyski, Kielce, Poland, 27-400
      • Regeneron Investigational Site
  • Malopolska
    • Krakow, Malopolska, Poland, 31-011
      • Regeneron Investigational Site
    • Kraków, Malopolska, Poland, 30 363
      • Regeneron Investigational Site
  • Slaskie
    • Katowice, Slaskie, Poland, 40-648
      • Regeneron Investigational Site
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE1 7EH
      • Regeneron Investigational Site
  • Lancashire
    • Manchester, Lancashire, United Kingdom, M13 9WL
      • Regeneron Investigational Site
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2TH
      • Regeneron Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Regeneron Investigational Site
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Regeneron Investigational Site
  • California
    • Bakersfield, California, United States, 93309
      • Regeneron Investigational Site
    • Long Beach, California, United States, 90808
      • Regeneron Investigational Site
    • Los Angeles, California, United States, 90027
      • Regeneron Investigational Site
    • Mission Viejo, California, United States, 92691
      • Regeneron Investigational Site
    • Orange, California, United States, 92868
      • Regeneron Investigational Site
    • Palo Alto, California, United States, 92304
      • Regeneron Investigational Site
    • Rolling Hills Estates, California, United States, 90274
      • Regeneron Investigational Site
    • San Diego, California, United States, 92123
      • Regeneron Investigational Site
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Regeneron Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Regeneron Investigational Site
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Regeneron Investigational Site
    • Tampa, Florida, United States, 33613
      • Regeneron Investigational Site
    • Tampa, Florida, United States, 33624
      • Regeneron Investigational Site
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Regeneron Investigational Site
    • Macon, Georgia, United States, 31217
      • Regeneron Investigational Site
    • Sandy Springs, Georgia, United States, 30328
      • Regeneron Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Regeneron Investigational Site
    • Skokie, Illinois, United States, 60077
      • Regeneron Investigational Site
  • Indiana
    • Plainfield, Indiana, United States, 46168
      • Regeneron Investigational Site
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Regeneron Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Regeneron Investigational Site
    • Boston, Massachusetts, United States, 02116
      • Regeneron Investigational Site
  • Michigan
    • Ypsilanti, Michigan, United States, 48197
      • Regeneron Investigational Site
  • Minnesota
    • Plymouth, Minnesota, United States, 55441
      • Regeneron Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Regeneron Investigational Site
  • New York
    • Forest Hills, New York, United States, 11375
      • Regeneron Investigational Site
    • New York, New York, United States, 10029
      • Regeneron Investigational Site
    • Rochester, New York, United States, 14642
      • Regeneron Investigational Site
  • Ohio
    • Gahanna, Ohio, United States, 43230
      • Regeneron Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Regeneron Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Regeneron Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Regeneron Investigational Site
    • North Charleston, South Carolina, United States, 29420
      • Regeneron Investigational Site
  • Texas
    • Bellaire, Texas, United States, 77401-3505
      • Regeneron Investigational Site
    • Fort Worth, Texas, United States, 76244
      • Regeneron Investigational Site
    • San Antonio, Texas, United States, 78218
      • Regeneron Investigational Site
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Regeneron Investigational Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Regeneron Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participated in a prior dupilumab study in pediatric participants with AD and adequately completed the visits and assessments required for both the treatment and follow-up periods, as defined in the prior study protocol
• PFP Sub-Study Only:
• Age ≥2 to <12 years at time of screening
• Body weight ≥5 kg and <60 kg at time of screening
• Must have received the same dupilumab dose regimen to be used in the PFP sub-study during the previous 12 weeks in the main OLE study using the prefilled syringe, as defined in the protocol

Key Exclusion Criteria:

• Participants who, during their participation in a prior dupilumab study developed an adverse event (AE) or serious adverse event (SAE) deemed related to study drug which could indicate that continued treatment with study drug may present an unreasonable risk for the patient
• Participants, who during the participation in a prior Dupilumab study, developed an AE that was deemed related to study drug and led to study treatment discontinuation, which in the opinion of the investigator or medical monitor could indicate that continued treatment with study drug may present an unreasonable risk for the patient
• Treatment with an investigational drug, other than dupilumab, within 8 weeks or within 5 half-lives (if known), whichever is longer, before the baseline visit
• Having used immunosuppressive/immunomodulating drugs within 4 weeks before the baseline visit
• Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit
• Diagnosed active endoparasitic infections or at high risk of these infections
• Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the participant's participation in the study
• PFP Sub-study Only:
• Poor compliance as defined by having missed 1 or more of the planned last 3 injections in the main OLE study prior to entering the sub-study
• Switched dupilumab doses within the past 12 weeks
• Meet criteria for temporary/permanent discontinuation of study drug at time of screening into PFP sub-study, as defined in the protocol.

Note: Other protocol defined Inclusion / Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Body weight ≥60 kg; Administered every two weeks (Q2W)	Drug: Dupilumab; Weight-tiered dosing administered subcutaneous (SC); Other Names: REGN668; SAR231893; DUPIXENT®
Experimental: Body weight 30 kg to <60 kg; Administered Q2W	Drug: Dupilumab; Weight-tiered dosing administered subcutaneous (SC); Other Names: REGN668; SAR231893; DUPIXENT®
Experimental: Body weight 15 kg to <30 kg; Administered every 4 weeks (Q4W)	Drug: Dupilumab; Weight-tiered dosing administered subcutaneous (SC); Other Names: REGN668; SAR231893; DUPIXENT®
Experimental: Body weight 5 kg to <15 kg; Administered Q4W	Drug: Dupilumab; Weight-tiered dosing administered subcutaneous (SC); Other Names: REGN668; SAR231893; DUPIXENT®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of treatment-emergent adverse events (TEAEs) per participant year from baseline through the last study visit		Baseline up to week 272
Number of participants with at least one TEAE per participant year from baseline through the last study visit		Baseline up to week 272
OPTIONAL SUB-STUDY: Pharmacokinetic (PK) of dupilumab: Peak concentration (Cmax)	Peak serum concentration after multiple doses of dupilumab administered using the PFP (test) relative to the prefilled syringe (reference)	Up to week 16
OPTIONAL SUB-STUDY: PK of dupilumab: Trough concentration (Ctrough)	Drug concentration in serum after multiple doses of dupilumab administered using the PFP (test) relative to the prefilled syringe (reference)	Up to week 16
OPTIONAL SUB-STUDY: Incidence of TEAEs during the 12-week PFP treatment period and during entire sub-study		Up to week 16
OPTIONAL SUB-STUDY: Incidence of SAEs during the 12-week PFP treatment period and during entire sub-study		Up to week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment-emergent serious adverse events (SAEs) from baseline through the last study visit		Baseline up to week 272
Incidence of TEAEs of special interest from baseline through the last study visit		Baseline up to week 272
Proportion of participants with an Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) at all in-clinic visits post-baseline		Baseline up to week 272
Proportion of participants with Eczema Area and Severity Index (EASI)-75 (≥75% reduction in EASI from baseline of parent study) response at all in-clinic visits post-baseline		Baseline up to week 272
Change from baseline in EASI score at all in-clinic visits post-baseline		Baseline up to week 272
Percent change from baseline in EASI at all in-clinic visits post-baseline		Baseline up to week 272
Change from baseline in Body Surface Area (BSA) affected by AD (BSA) at all in-clinic visits post-baseline		Baseline up to week 272
Percent change from baseline in SCORing Atopic Dermatitis (SCORAD) at all in-clinic visits post-baseline		Baseline up to week 272
Change from baseline in Children's Dermatology Life Quality Index (CDLQI) for participants ≥4 years of age at all in-clinic visits post-baseline in which the assessments are planned to be performed		Baseline up to week 272
Change from baseline in Infants' Dermatology Quality of Life Index (IDQOL) for participants <4 years of age at all in-clinic visits post-baseline in which the assessments are planned to be performed		Baseline up to week 272
Proportion of responders (defined as participants with IGA 0 or 1) who maintain IGA 0 or 1 during at least 75% of the subsequent* visits during the treatment period	*Subsequent refers to the visits following the first visit at which IGA 0 or 1 is achieved.	Baseline to week 260
For responders (defined as participants with IGA 0 or 1), median percentage of subsequent* visits during the treatment period, at which IGA 0 or 1 is maintained	*Subsequent refers to the visits following the first visit at which IGA 0 or 1 is achieved.	Baseline to week 260
Number of AD flares during the study	AD flares are defined as worsening of the disease that requires escalation/intensification of AD treatment	Baseline to week 272
Annualize event rate of AD flares during the study	AD flares are defined as worsening of the disease that requires escalation/intensification of AD treatment	Baseline to week 272
Proportion of participants with at least one flare during the study	AD flares are defined as worsening of the disease that requires escalation/intensification of AD treatment	Baseline to week 272
Proportion of well-controlled weeks	Well-controlled weeks are those for which participants or parents/caregivers answer "Yes" AND during which no rescue treatments were administered	Baseline to week 272
OPTIONAL SUB-STUDY: Incidence and titer of treatment-emergent anti-drug antibodies (ADA) (PFP Sub-Study)		Up to 16 weeks

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi

Publications and helpful links

General Publications

• Blauvelt A, Guttman-Yassky E, Paller AS, Simpson EL, Cork MJ, Weisman J, Browning J, Soong W, Sun X, Chen Z, Kosloski MP, Kamal MA, Delevry D, Chuang CC, O'Malley JT, Bansal A. Long-Term Efficacy and Safety of Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis: Results Through Week 52 from a Phase III Open-Label Extension Trial (LIBERTY AD PED-OLE). Am J Clin Dermatol. 2022 May;23(3):365-383. doi: 10.1007/s40257-022-00683-2. Epub 2022 May 14.
• Paller AS, Tan JKL, Bagel J, Rossi AB, Shumel B, Zhang H, Abramova A. IGAxBSA composite for assessing disease severity and response in patients with atopic dermatitis. Br J Dermatol. 2022 Mar;186(3):496-507. doi: 10.1111/bjd.20872. Epub 2022 Feb 25.
• Bansal A, Simpson EL, Paller AS, Siegfried EC, Blauvelt A, de Bruin-Weller M, Corren J, Sher L, Guttman-Yassky E, Chen Z, Daizadeh N, Kamal MA, Shumel B, Mina-Osorio P, Mannent L, Patel N, Graham NMH, Khokhar FA, Ardeleanu M. Conjunctivitis in Dupilumab Clinical Trials for Adolescents with Atopic Dermatitis or Asthma. Am J Clin Dermatol. 2021 Jan;22(1):101-115. doi: 10.1007/s40257-020-00577-1.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2015
• Primary Completion (Anticipated): August 19, 2026
• Study Completion (Anticipated): August 19, 2026

Study Registration Dates

• First Submitted: November 11, 2015
• First Submitted That Met QC Criteria: November 19, 2015
• First Posted (Estimate): November 23, 2015

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Eczema
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: R668-AD-1434; 2015-001396-40 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No