Clinical trial NCT02612454: Study to Assess the Long-term Safety of Dupilumab Administered in Participants ≥6 Months to <18 Years of Age With Atopic Dermatitis (AD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Atopic Dermatitis
Keywords: Eczema
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2015-11-23
Enrollment: 880
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Rate of treatment-emergent adverse events (TEAEs) per participant year from baseline through the last study visit
timeFrame: Baseline up to week 272
measure: Number of participants with at least one TEAE per participant year from baseline through the last study visit
timeFrame: Baseline up to week 272
measure: OPTIONAL SUB-STUDY: Pharmacokinetic (PK) of dupilumab: Peak concentration (Cmax)
timeFrame: Up to week 16
measure: OPTIONAL SUB-STUDY: PK of dupilumab: Trough concentration (Ctrough)
timeFrame: Up to week 16
measure: OPTIONAL SUB-STUDY: Incidence of TEAEs during the 12-week PFP treatment period and during entire sub-study
timeFrame: Up to week 16
measure: OPTIONAL SUB-STUDY: Incidence of SAEs during the 12-week PFP treatment period and during entire sub-study
timeFrame: Up to week 16
Secondary outcomes:
measure: Number of treatment-emergent serious adverse events (SAEs) from baseline through the last study visit
timeFrame: Baseline up to week 272
measure: Incidence of TEAEs of special interest from baseline through the last study visit
timeFrame: Baseline up to week 272
measure: 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
timeFrame: Baseline up to week 272
measure: 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
timeFrame: Baseline up to week 272
measure: Change from baseline in EASI score at all in-clinic visits post-baseline
timeFrame: Baseline up to week 272
measure: Percent change from baseline in EASI at all in-clinic visits post-baseline
timeFrame: Baseline up to week 272
measure: Change from baseline in Body Surface Area (BSA) affected by AD (BSA) at all in-clinic visits post-baseline
timeFrame: Baseline up to week 272
measure: Percent change from baseline in SCORing Atopic Dermatitis (SCORAD) at all in-clinic visits post-baseline
timeFrame: Baseline up to week 272
measure: 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
timeFrame: Baseline up to week 272
measure: 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
timeFrame: Baseline up to week 272
measure: 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
timeFrame: Baseline to week 260
measure: 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
timeFrame: Baseline to week 260
measure: Number of AD flares during the study
timeFrame: Baseline to week 272
measure: Annualize event rate of AD flares during the study
timeFrame: Baseline to week 272
measure: Proportion of participants with at least one flare during the study
timeFrame: Baseline to week 272
measure: Proportion of well-controlled weeks
timeFrame: Baseline to week 272
measure: OPTIONAL SUB-STUDY: Incidence and titer of treatment-emergent anti-drug antibodies (ADA) (PFP Sub-Study)
timeFrame: Up to 16 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Regeneron Investigational Site
state: Alabama
city: Gilbert
country: United States
facility: Regeneron Investigational Site
state: Arizona
city: Bakersfield
country: United States
facility: Regeneron Investigational Site
state: California
city: Long Beach
country: United States
facility: Regeneron Investigational Site
state: California
city: Los Angeles
country: United States
facility: Regeneron Investigational Site
state: California
city: Mission Viejo
country: United States
facility: Regeneron Investigational site
state: California
city: Orange
country: United States
facility: Regeneron Investigational Site
state: California
city: Palo Alto
country: United States
facility: Regeneron Investigational Site
state: California
city: Rolling Hills Estates
country: United States
facility: Regeneron Investigational Site
state: California
city: San Diego
country: United States
facility: Regeneron Investigational Site
state: California
city: Centennial
country: United States
facility: Regeneron Investigational Site
state: Colorado
city: Washington
country: United States
facility: Regeneron Investigational Site
state: District of Columbia
city: Coral Gables
country: United States
facility: Regeneron Investigational Site
state: Florida
city: Tampa
country: United States
facility: Regeneron Investigational Site
state: Florida
city: Tampa
country: United States
facility: Regeneron Investigational Site
state: Florida
city: Columbus
country: United States
facility: Regeneron Investigational Site
state: Georgia
city: Macon
country: United States
facility: Regeneron Investigational Site
state: Georgia
city: Sandy Springs
country: United States
facility: Regeneron Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Regeneron Investigational Site
state: Illinois
city: Skokie
country: United States
facility: Regeneron Investigational Site
state: Illinois
city: Plainfield
country: United States
facility: Regeneron Investigational site
state: Indiana
city: Rockville
country: United States
facility: Regeneron Investigational Site
state: Maryland
city: Boston
country: United States
facility: Regeneron Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Regeneron Investigational Site
state: Massachusetts
city: Ypsilanti
country: United States
facility: Regeneron Investigational Site
state: Michigan
city: Plymouth
country: United States
facility: Regeneron Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: Regeneron Investigational Site
state: Missouri
city: Forest Hills
country: United States
facility: Regeneron Investigational Site
state: New York
city: New York
country: United States
facility: Regeneron Investigational Site
state: New York
city: Rochester
country: United States
facility: Regeneron Investigational Site
state: New York
city: Gahanna
country: United States
facility: Regeneron Investigational Site
state: Ohio
city: Portland
country: United States
facility: Regeneron Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: Regeneron Investigational site
state: Pennsylvania
city: Charleston
country: United States
facility: Regeneron Investigational Site
state: South Carolina
city: North Charleston
country: United States
facility: Regeneron Investigational Site
state: South Carolina
city: Bellaire
country: United States
facility: Regeneron Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: Regeneron Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Regeneron Investigational Site
state: Texas
city: Norfolk
country: United States
facility: Regeneron Investigational Site
state: Virginia
city: Seattle
country: United States
facility: Regeneron Investigational Site
state: Washington
city: Calgary
country: Canada
facility: Regeneron Investigational Site
state: Alberta
city: Surrey
country: Canada
facility: Regeneron Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Regeneron Investigational Site
state: Manitoba
city: Markham
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Peterborough
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Waterloo
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: Regeneron Investigational Site
state: Quebec
city: Kutna Hora
country: Czechia
facility: Regeneron Investigational Site
city: Prague
country: Czechia
facility: Regeneron Investigational Site
city: Ústí Nad Labem
country: Czechia
facility: Regeneron Investigational Site
city: Tuebingen
country: Germany
facility: Regeneron Study Site
state: Baden-Wuerttemberg
city: Frankfurt
country: Germany
facility: Regeneron Investigational Site
state: Hessen
city: Muenster
country: Germany
facility: Regeneron Investigational Site
state: North Rhine-Westphal
city: Dresden
country: Germany
facility: Regeneron Investigational Site
state: Sachsen
city: Gera
country: Germany
facility: Regeneron Investigational Site
city: Hamburg
country: Germany
facility: Regeneron Investigational Site
city: Muenchen
country: Germany
facility: Regeneron Study Site
city: Munich
country: Germany
facility: Regeneron Investigational Site
city: Szolnok
country: Hungary
facility: Regeneron Investigational Site
state: Jasz-Nagykun-Szolnok
city: Kaposvar
country: Hungary
facility: Regeneron Investigational Site
city: Miskolc
country: Hungary
facility: Regeneron Investigational Site
city: Szeged
country: Hungary
facility: Regeneron Investigational Site
city: Wroclaw
country: Poland
facility: Regeneron Investigational Site
state: Dolnoslaskie
city: Wrocław
country: Poland
facility: Regeneron Investigational Site
state: Dolnoslaskie
city: Ostrowiec Świętokrzyski
country: Poland
facility: Regeneron Investigational Site
state: Kielce
city: Krakow
country: Poland
facility: Regeneron Investigational Site
state: Malopolska
city: Kraków
country: Poland
facility: Regeneron Investigational Site
state: Malopolska
city: Katowice
country: Poland
facility: Regeneron Investigational Site
state: Slaskie
city: Białystok
country: Poland
facility: Regeneron Investigational Site
city: Bydgoszcz
country: Poland
facility: Regeneron Investigational Site
city: Chorzow
country: Poland
facility: Regeneron Investigational Site
city: Gdańsk
country: Poland
facility: Regeneron Investigational Site
city: Katowice
country: Poland
facility: Regeneron Investigational Site
city: Kraków
country: Poland
facility: Regeneron Investigational Site
city: Lodz
country: Poland
facility: Regeneron Investigational Site
city: Warszawa
country: Poland
facility: Regeneron Investigational Site
city: Warszawa
country: Poland
facility: Regeneron Investigational Site
city: Warszawa
country: Poland
facility: Regeneron Investigational Site
city: Warszawa
country: Poland
facility: Regeneron Investigational Site
city: London
country: United Kingdom
facility: Regeneron Investigational Site
state: Greater London
city: Manchester
country: United Kingdom
facility: Regeneron Investigational Site
state: Lancashire
city: Sheffield
country: United Kingdom
facility: Regeneron Investigational Site
state: South Yorkshire
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.