Back to resultsA Study to Determine the Safety and Tolerability of Dupilumab (REGN668/SAR231893) in Patients Aged ≥6 to <18 Years With Atopic Dermatitis (Eczema)
Primary Purpose
Atopic Dermatitis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Dupilumab
Sponsored by
About this trial
This is an interventional treatment trial for Atopic Dermatitis focused on measuring Eczema
Eligibility Criteria
Key Inclusion Criteria:
- Male or female patients ≥6 to <18 years of age with a diagnosis of 1. Atopic Dermatitis whose disease cannot be adequately controlled with topical medications
Minimum disease severity, as defined by Investigator's Global Assessment (IGA)
- IGA = 3 or 4 in adolescents ≥12 to <18 year of age
- IGA = 4 in children ≥6 to <12 years of age
Key Exclusion Criteria:
- Recent treatment (within specific time windows before the baseline visit) with systemic immunosuppressive agents for eg. Systemic corticosteroids, live (attenuated) vaccines and other investigational drugs including biologics
History of any of the following infections:
- Any systemic infection requiring treatment within 4 weeks before the baseline visit
- Superficial skin infections within 1 week before the baseline visit
- Known history of HIV infection
- History of seropositivity to hepatitis B or C screening tests
- History of clinical endoparasitosis (ie, helminthic infection) within 12 months before the baseline visit, or high risk of helminthic infection, unless subsequent medical assessments (e.g. stool exam, blood tests, etc.) have ruled out the possibility of parasite infection/infestation
- History of malignancy within 5 years before the baseline visit
- Persistent (confirmed by repeated tests ≥2 weeks apart) elevated transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) more than 3 times the upper limit of normal (ULN) during the screening period
- Presence of any severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's participation in the study
- Presence of skin comorbidities that may interfere with study assessments
- Females patients who are pregnant or breastfeeding
- Female patients who are of reproductive potential and are sexually active, who are unwilling to use adequate methods of contraception
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Arm Description
Cohort 1 will receive dupilumab dosing regimen 1
Cohort 2 will receive dupilumab dosing regimen 2
Outcomes
Primary Outcome Measures
Pharmacokinetics (PK) of Dupilumab: Maximum Plasma Concentration Observed (Cmax) After Single Administration
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.
PK of Dupilumab: Area Under the Plasma Concentration Versus Time Curve (AUClast) After Single Administration
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.
PK of Dupilumab: Trough Dupilumab Concentration in Serum (Ctrough) Before 3rd and 4th Repeated Dose
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.
Secondary Outcome Measures
Percent Reduction From Baseline in Eczema Area and Severity Index (EASI) at Week 12
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).
Percent Reduction From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 12
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 values were imputed by LOCF.
Percent Reduction From Baseline in Pruritus Numerical Rating Scale (NRS) at Week 12
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.
Percentage of Subjects With Investigator Global Assessment (IGA) Score of "0" or "1" (Clear or Almost Clear) at 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.
Percent Reduction From Baseline in Body Surface Area (BSA) at 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.
Full Information
NCT ID
NCT02407756
First Posted
March 31, 2015
Last Updated
November 24, 2020
Sponsor
Regeneron Pharmaceuticals
Collaborators
Sanofi
1. Study Identification
Unique Protocol Identification Number
NCT02407756
Brief Title
A Study to Determine the Safety and Tolerability of Dupilumab (REGN668/SAR231893) in Patients Aged ≥6 to <18 Years With Atopic Dermatitis (Eczema)
Official Title
A Phase 2a Study Investigating the Safety, Pharmacokinetics, Immunogenicity, and Exploratory Efficacy of Dupilumab in Patients Aged ≥6 to <18 Years With Atopic Dermatitis
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
March 31, 2015 (Actual)
Primary Completion Date
March 31, 2016 (Actual)
Study Completion Date
March 31, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
Collaborators
Sanofi
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis
Keywords
Eczema
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
78 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Cohort 1 will receive dupilumab dosing regimen 1
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Cohort 2 will receive dupilumab dosing regimen 2
Intervention Type
Drug
Intervention Name(s)
Dupilumab
Other Intervention Name(s)
REGN668(SAR231893)
Primary Outcome Measure Information:
Title
Pharmacokinetics (PK) of Dupilumab: Maximum Plasma Concentration Observed (Cmax) After Single Administration
Description
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.
Time Frame
Day 2, 4, 8, 15, 22, 29, 36, 43, and 50
Title
PK of Dupilumab: Area Under the Plasma Concentration Versus Time Curve (AUClast) After Single Administration
Description
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.
Time Frame
Day 2, 4, 8, 15, 22, 29, 36, 43, and 50
Title
PK of Dupilumab: Trough Dupilumab Concentration in Serum (Ctrough) Before 3rd and 4th Repeated Dose
Description
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.
Time Frame
Pre-dose on Day 71 and Day 85
Secondary Outcome Measure Information:
Title
Percent Reduction From Baseline in Eczema Area and Severity Index (EASI) at Week 12
Description
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).
Time Frame
Baseline to Week 12 (one week after last dose)
Title
Percent Reduction From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 12
Description
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 values were imputed by LOCF.
Time Frame
Baseline to Week 12 (one week after last dose)
Title
Percent Reduction From Baseline in Pruritus Numerical Rating Scale (NRS) at Week 12
Description
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.
Time Frame
Baseline to Week 12 (one week after last dose)
Title
Percentage of Subjects With Investigator Global Assessment (IGA) Score of "0" or "1" (Clear or Almost Clear) at Week 12
Description
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.
Time Frame
Week 12
Title
Percent Reduction From Baseline in Body Surface Area (BSA) at Week 12
Description
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.
Time Frame
Baseline to Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Male or female patients ≥6 to <18 years of age with a diagnosis of 1. Atopic Dermatitis whose disease cannot be adequately controlled with topical medications
Minimum disease severity, as defined by Investigator's Global Assessment (IGA)
IGA = 3 or 4 in adolescents ≥12 to <18 year of age
IGA = 4 in children ≥6 to <12 years of age
Key Exclusion Criteria:
Recent treatment (within specific time windows before the baseline visit) with systemic immunosuppressive agents for eg. Systemic corticosteroids, live (attenuated) vaccines and other investigational drugs including biologics
History of any of the following infections:
Any systemic infection requiring treatment within 4 weeks before the baseline visit
Superficial skin infections within 1 week before the baseline visit
Known history of HIV infection
History of seropositivity to hepatitis B or C screening tests
History of clinical endoparasitosis (ie, helminthic infection) within 12 months before the baseline visit, or high risk of helminthic infection, unless subsequent medical assessments (e.g. stool exam, blood tests, etc.) have ruled out the possibility of parasite infection/infestation
History of malignancy within 5 years before the baseline visit
Persistent (confirmed by repeated tests ≥2 weeks apart) elevated transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) more than 3 times the upper limit of normal (ULN) during the screening period
Presence of any severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's participation in the study
Presence of skin comorbidities that may interfere with study assessments
Females patients who are pregnant or breastfeeding
Female patients who are of reproductive potential and are sexually active, who are unwilling to use adequate methods of contraception
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
City
Markham
State/Province
Ontario
Country
Canada
City
Peterborough
State/Province
Ontario
Country
Canada
City
Waterloo
State/Province
Ontario
Country
Canada
City
Windsor
State/Province
Ontario
Country
Canada
City
Kutna Hora
Country
Czechia
City
Prague
Country
Czechia
City
Dresden
Country
Germany
City
Frankfurt
Country
Germany
City
Gera
Country
Germany
City
Hamburg
Country
Germany
City
Kiel
Country
Germany
City
Luebeck
Country
Germany
City
Muenster
Country
Germany
City
Munich
Country
Germany
City
Tuebingen
Country
Germany
City
Kaposvar
Country
Hungary
City
Miskolc
Country
Hungary
City
Szeged
Country
Hungary
City
Szolnok
Country
Hungary
City
Katowice
Country
Poland
City
Krakow
Country
Poland
City
Lodz
Country
Poland
City
Warszawa
Country
Poland
City
Wroclaw
Country
Poland
City
Manchester
Country
United Kingdom
City
Sheffield
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
35567671
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.
Results Reference
derived
PubMed Identifier
31595499
Citation
Cork MJ, Thaci D, Eichenfield LF, Arkwright PD, Hultsch T, Davis JD, Zhang Y, Zhu X, Chen Z, Li M, Ardeleanu M, Teper A, Akinlade B, Gadkari A, Eckert L, Kamal MA, Ruddy M, Graham NMH, Pirozzi G, Stahl N, DiCioccio AT, Bansal A. 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. Br J Dermatol. 2020 Jan;182(1):85-96. doi: 10.1111/bjd.18476. Epub 2019 Oct 8.
Results Reference
derived
Learn more about this trial
A Study to Determine the Safety and Tolerability of Dupilumab (REGN668/SAR231893) in Patients Aged ≥6 to <18 Years With Atopic Dermatitis (Eczema)
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