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NCT02407756

A Study to Determine the Safety and Tolerability of Dupilumab (REGN668/SAR231893) in Patients Aged ≥6 to <18 Years With Atopic Dermatitis (Eczema)

Completed Phase 2 Results posted Last updated 27 November 2020
What this trial tests

Phase 2 trial testing Dupilumab in Atopic Dermatitis in 78 participants. Completed in 31 March 2016.

Timeline
31 March 2015
Primary endpoint
31 March 2016
31 March 2016

Quick facts

Lead sponsorRegeneron Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment78
Start date31 March 2015
Primary completion31 March 2016
Estimated completion31 March 2016
Sites26 locations across United Kingdom, Germany, Poland, Hungary, Canada, Czechia

Drugs / interventions tested

Conditions studied

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

Adults 6 to 17, any sex, with Atopic Dermatitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pharmacokinetics (PK) of Dupilumab: Maximum Plasma Concentration Observed (Cmax) After Single Administration Primary · Day 2, 4, 8, 15, 22, 29, 36, 43, and 50

Peak dupilumab concentration in serum following single dose administration. Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of the study drug.

GroupValue95% CI
Dupilumab 2mg/kg: Adolescents9.91± 2.15
Dupilumab 2mg/kg: Children14.3± 5.9
Dupilumab 4mg/kg: Adolescents23.1± 8.71
Dupilumab 4mg/kg: Children32.4± 7.04
PK of Dupilumab: Area Under the Plasma Concentration Versus Time Curve (AUClast) After Single Administration Primary · Day 2, 4, 8, 15, 22, 29, 36, 43, and 50

Mean AUC estimates were calculated using mean concentration data at each time point, using a non-compartmental approach (NCA). Calculated AUClast (computed from time zero to the time of the last positive concentration) are presented. Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of the study drug.

GroupValue95% CI
Dupilumab 2mg/kg: Adolescents104± NA
Dupilumab 2mg/kg: Children160± NA
Dupilumab 4mg/kg: Adolescents362± NA
Dupilumab 4mg/kg: Children330± NA
PK of Dupilumab: Trough Dupilumab Concentration in Serum (Ctrough) Before 3rd and 4th Repeated Dose Primary · Pre-dose on Day 71 and Day 85

Analysis was performed on PK analysis set that included all treated subjects who received the study medication and had at least 1 quantified (non-missing) result for dupilumab concentration following the first dose of study drug.

Day 71
GroupValue95% CI
Dupilumab 2mg/kg: Adolescents10.4± 7.16
Dupilumab 2mg/kg: Children17.2± 8.44
Dupilumab 4mg/kg: Adolescents32.8± 18.9
Dupilumab 4mg/kg: Children42.1± 19.4
Day 85
GroupValue95% CI
Dupilumab 2mg/kg: Adolescents18.5± 12.4
Dupilumab 2mg/kg: Children28± 12.9
Dupilumab 4mg/kg: Adolescents58.8± 24.4
Dupilumab 4mg/kg: Children60.3± 36.3
Percent Reduction From Baseline in Eczema Area and Severity Index (EASI) at Week 12 Secondary · Baseline to Week 12 (one week after last dose)

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 to 72 points, with the higher scores reflecting the worse severity of AD. Analysis was performed on safety analysis set (SAF) that included all subjects who received any study drug. Data after rescue treatment use during the Part B period were set to missing, then missing values were imputed by last observation carried forward (LOCF

GroupValue95% CI
Dupilumab 2mg/kg: Adolescents-66.4± 29.25
Dupilumab 2mg/kg: Children-76.2± 25.48
Dupilumab 4mg/kg: Adolescents-69.7± 24.48
Dupilumab 4mg/kg: Children-63.4± 25.37
Percent Reduction From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 12 Secondary · Baseline to Week 12 (one week after last dose)

SCORAD is a clinical tool for assessing the severity of atopic dermatitis developed by the European Task Force on Atopic Dermatitis ("Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis". Dermatology (Basel) 186 (1): 23-31. 1993). Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 \[absent disease\] to 103 \[severe disease\]). Analysis was performed on SAF. Data after rescue treatment use during the Part B period were set to missing, then missing val

GroupValue95% CI
Dupilumab 2mg/kg: Adolescents-47.7± 27.27
Dupilumab 2mg/kg: Children-57.5± 23.1
Dupilumab 4mg/kg: Adolescents-43.4± 25.38
Dupilumab 4mg/kg: Children-46.9± 24.31
Percent Reduction From Baseline in Pruritus Numerical Rating Scale (NRS) at Week 12 Secondary · Baseline to Week 12 (one week after last dose)

Pruritus NRS scale is an assessment tool that is used to report the intensity of subject's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Subjects were asked the following question: how would a subject rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Analysis was performed on SAF. Data after rescue treatment use during the Part B period were set to missing, then missing values were imputed by LOCF.

GroupValue95% CI
Dupilumab 2mg/kg: Adolescents-30.8± 68.35
Dupilumab 2mg/kg: Children-41.6± 35.32
Dupilumab 4mg/kg: Adolescents-37.6± 34.42
Dupilumab 4mg/kg: Children-39.6± 40.88
Percentage of Subjects With Investigator Global Assessment (IGA) Score of "0" or "1" (Clear or Almost Clear) at Week 12 Secondary · Week 12

IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Analysis was performed on SAF. Subjects with rescue treatment usage during the Part B period were specified as non-responders from the time the rescue was used.

GroupValue95% CI
Dupilumab 2mg/kg: Adolescents10
Dupilumab 2mg/kg: Children16.7
Dupilumab 4mg/kg: Adolescents35
Dupilumab 4mg/kg: Children21.1
Percent Reduction From Baseline in Body Surface Area (BSA) at Week 12 Secondary · Baseline to Week 12

Body surface area affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined. Analysis was performed on SAF.

GroupValue95% CI
Dupilumab 2mg/kg: Adolescents-61± 31.08
Dupilumab 2mg/kg: Children-70± 31.93
Dupilumab 4mg/kg: Adolescents-60.4± 34.04
Dupilumab 4mg/kg: Children-50± 30.8

Adverse events — posted to ClinicalTrials.gov

Time frame: All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dupilumab 2mg/kg: Adolescents
Serious: 1/20 (5%)
Deaths: 0/20
Dupilumab 2mg/kg: Children
Serious: 0/18 (0%)
Deaths: 0/18
Dupilumab 4 mg/kg: Adolescents
Serious: 1/20 (5%)
Deaths: 0/20
Dupilumab 4 mg/kg: Children
Serious: 2/19 (11%)
Deaths: 0/19

Serious adverse events (5 terms)

ReactionSystemDupilumab 2mg/kg: Adolesce…Dupilumab 2mg/kg: ChildrenDupilumab 4 mg/kg: Adolesc…Dupilumab 4 mg/kg: Children
PalpitationsCardiac disorders
Dermatitis atopicSkin and subcutaneous tissue disorders
Staphylococcal skin infectionInfections and infestations
Arthritis bacterialInfections and infestations
Dermatitis infectedInfections and infestations
Other adverse events (99 terms — click to expand)

ReactionSystemDupilumab 2mg/kg: Adolesce…Dupilumab 2mg/kg: ChildrenDupilumab 4 mg/kg: Adolesc…Dupilumab 4 mg/kg: Children
NasopharyngitisInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
Dermatitis atopicSkin and subcutaneous tissue disorders
Abdominal pain upperGastrointestinal disorders
VomitingGastrointestinal disorders
NauseaGastrointestinal disorders
PyrexiaGeneral disorders
Dermatitis infectedInfections and infestations
InfluenzaInfections and infestations
RhinitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
DizzinessNervous system disorders
HeadacheNervous system disorders
Rhinitis allergicRespiratory, thoracic and mediastinal disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
CyanosisCardiac disorders
EosinophiliaBlood and lymphatic system disorders
Conjunctivitis allergicEye disorders
Dermoid cystCongenital, familial and genetic disorders
Aphthous stomatitisGastrointestinal disorders
CheilitisGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
ChillsGeneral disorders
Chest painGeneral disorders
Mouth ulcerationGastrointestinal disorders
Injection site urticariaGeneral disorders
Injection site swellingGeneral disorders
Injection site irritationGeneral disorders
Injection site erythemaGeneral disorders
Feeling of body temperature changeGeneral disorders
Food allergyImmune system disorders
Bacterial disease carrierInfections and infestations
Acute tonsillitisInfections and infestations
HypersensitivityImmune system disorders
Allergic oedemaImmune system disorders
Gastrointestinal infectionInfections and infestations
ConjunctivitisInfections and infestations
Croup infectiousInfections and infestations

Most-reported serious reactions: Palpitations, Dermatitis atopic, Staphylococcal skin infection, Arthritis bacterial, Dermatitis infected.

Data from ClinicalTrials.gov NCT02407756 adverse events section.

Sponsor's own description

The primary objective of the study is to characterize the safety and pharmacokinetics (PK) of dupilumab in pediatric patients with moderate-to-severe atopic dermatitis (AD) (for adolescents ≥12 to \<18 years of age) or severe AD (for children ≥6 to \<12 years of age). The secondary objective of the study is to explore the immunogenicity and efficacy of dupilumab in pediatric patients with moderate-to-severe AD (for adolescents ≥12 to \<18 years of age) or severe AD (for children ≥6 to \<12 years of age).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Pathophysiology of atopic dermatitis: Clinical implications.
    Kim J, Kim BE, Leung DYM. · · 2019 · cited 368× · PMID 30819278 · DOI 10.2500/aap.2019.40.4202
  2. Immunologic, microbial, and epithelial interactions in atopic dermatitis.
    Brunner PM, Leung DYM, Guttman-Yassky E. · · 2018 · cited 129× · PMID 29126710 · DOI 10.1016/j.anai.2017.09.055
  3. Dupilumab in adolescents with uncontrolled moderate-to-severe atopic dermatitis: results from a phase IIa open-label trial and subsequent phase III open-label extension.
    Cork MJ, Thaçi D, Eichenfield LF, Arkwright PD, et al · · 2020 · cited 108× · PMID 31595499 · DOI 10.1111/bjd.18476
  4. Dupilumab Provides Favorable Safety and Sustained Efficacy for up to 3 Years in an Open-Label Study of Adults with Moderate-to-Severe Atopic Dermatitis.
    Beck LA, Thaçi D, Deleuran M, Blauvelt A, et al · · 2020 · cited 94× · PMID 32557382 · DOI 10.1007/s40257-020-00527-x
  5. 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).
    Blauvelt A, Guttman-Yassky E, Paller AS, Simpson EL, et al · · 2022 · cited 73× · PMID 35567671 · DOI 10.1007/s40257-022-00683-2
  6. A review of dupilumab in the treatment of atopic diseases.
    Thibodeaux Q, Smith MP, Ly K, Beck K, et al · · 2019 · cited 59× · PMID 30785362 · DOI 10.1080/21645515.2019.1582403
  7. Dupilumab provides favourable long-term safety and efficacy in children aged ≥ 6 to < 12 years with uncontrolled severe atopic dermatitis: results from an open-label phase IIa study and subsequent phase III open-label extension study.
    Cork MJ, Thaçi D, Eichenfield LF, Arkwright PD, et al · · 2021 · cited 52× · PMID 32969489 · DOI 10.1111/bjd.19460
  8. Moderate-to-severe atopic dermatitis in adolescents treated with dupilumab: A multicentre Italian real-world experience.
    Stingeni L, Bianchi L, Antonelli E, Caroppo ES, et al · · 2022 · cited 40× · PMID 35412683 · DOI 10.1111/jdv.18141

Verify or expand the search:

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Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02407756.

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