Efficacy and Safety of Dupilumab in Participants ≥12 to <18 Years of Age, With Moderate-to-severe Atopic Dermatitis

Dermatitis, Atopic Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Dupilumab Monotherapy in Patients ≥12 to <18 Years of Age, With Moderate-to-severe Atopic Dermatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03054428
• Other study ID #: R668-AD-1526
• Secondary ID: 2015-004458-16
• Status: Completed
• Phase: Phase 3
• Start date: March 21, 2017
• Est. completion date: June 5, 2018

Study information

• Verified date: July 2019
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study was to demonstrate the efficacy of dupilumab as a monotherapy in participants ≥12 years to <18 years of age with moderate-to-severe atopic dermatitis (AD). The secondary objective of the study was to assess the safety of dupilumab as a monotherapy in participants ≥12 years to <18 years of age with moderate-to-severe AD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 251
• Est. completion date: June 5, 2018
• Est. primary completion date: April 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

Inclusion Criteria:

• Male or female =12 to <18 years of age at time of screening visit

• Diagnosis of AD according to the American Academy of Dermatology consensus criteria at screening visit

• IGA =3 at screening and baseline visit

• EASI =16 at the screening and baseline visit

• Baseline Pruritus NRS average score for maximum itch intensity =4

• =10% BSA of AD involvement at the screening and baseline visits

• With documented recent history (within 6 months before the screening visit) of inadequate response to topical AD medication(s) or for whom topical treatments is medically inadvisable

Exclusion Criteria:

• Participation in a prior dupilumab clinical study

• Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 2 weeks before the baseline visit

• Having used immunosuppressive/immunomodulating drugs within 4 weeks before the baseline visit

• Body weight <30 kg at baseline

• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the baseline visit

• Known or suspected immunodeficiency, known history of human immunodeficiency virus (HIV) infection or HIV seropositivity at the screening visit, established diagnosis of HBV infection or HBV seropositivity at screening, established diagnosis of HCV infection or HCV seropositivity at screening

• History of malignancy before the baseline visit

• Diagnosed active endoparasitic infections or at high risk of these infections

• Patient is female who is pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study

• Patient is female of childbearing potential and sexually active, who is unwilling to use adequate methods of contraception throughout the duration of the study and for 120 days after the last dose of study drug

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Dermatitis
• Dermatitis, Atopic
• Dermatitis, Dermatitis Atopic
• Disease, Eczematous Skin
• Diseases Genetic, Genetic
• Diseases Inborn, Skin
• Eczema
• Eczema, Skin Diseases, Skin
• Hypersensitivity
• Hypersensitivity, Immediate
• Hypersensitivity, Immune System Diseases
• Immune System Diseases
• Moderate-to-Severe Atopic Dermatitis
• Skin Diseases
• Skin Diseases, Eczematous

Intervention

Drug:
• Dupilumab
Subcutaneous injection among the different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.
• Placebo
Subcutaneous injection among the different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.

Locations

Country	Name	City	State
Canada	Regeneron Investigational Site	Calgary	Alberta
Canada	Regeneron Investigational Site	Markham	Ontario
Canada	Regeneron Investigational Site	Ottawa	Ontario
Canada	Regeneron Investigational Site	Peterborough	Ontario
Canada	Regeneron Research Site	Richmond Hill	Ontario
Canada	Regeneron Investigational Site	Surrey	British Columbia
Canada	Regeneron Investigational Site	Surrey	British Columbia
Canada	Regeneron Investigational Site	Windsor	Ontario
Canada	Regeneron Investigational Site	Winnipeg	Manitoba
United States	Regeneron Investigational Site	Bakersfield	California
United States	Regeneron Investigational Site	Bellaire	Texas
United States	Regeneron Investigational Site	Bexley	Ohio
United States	Regeneron Investigational Site	Birmingham	Alabama
United States	Regeneron Investigational Site	Boston	Massachusetts
United States	Regeneron Investigational Site	Boston	Massachusetts
United States	Regeneron Investigational Site	Centennial	Colorado
United States	Regeneron Investigational Site	Chapel Hill	North Carolina
United States	Regeneron Investigational Site	Charleston	South Carolina
United States	Regeneron Investigational Site	Chicago	Illinois
United States	Regeneron Investigational Site	Denver	Colorado
United States	Regeneron Investigational Site	Evansville	Indiana
United States	Regeneron Investigational Site	Forest Hills	New York
United States	Regeneron Investigational Site	Gilbert	Arizona
United States	Regeneron Investigational Site	Indianapolis	Indiana
United States	Regeneron Investigational Site	Long Beach	California
United States	Regeneron Investigational Site	Macon	Georgia
United States	Regeneron Investigational Site	New York	New York
United States	Regeneron Investigational Site	Norfolk	Virginia
United States	Regeneron Investigational Site	Philadelphia	Pennsylvania
United States	Regeneron Investigational Site	Plainfield	Indiana
United States	Regeneron Investigational Site	Plymouth	Minnesota
United States	Regeneron Investigational Site	Portland	Oregon
United States	Regeneron Investigational Site	Portland	Oregon
United States	Regeneron Investigational Site	Rochester	New York
United States	Regeneron Investigational Site	Rockville	Maryland
United States	Regeneron Investigational Site	Rolling Hills Estates	California
United States	Regeneron Investigational Site	Saint Louis	Missouri
United States	Regeneron Investigational Site	San Antonio	Texas
United States	Regeneron Investigational Site	San Diego	California
United States	Regeneron Investigational Site	Sandy Springs	Georgia
United States	Regeneron Investigational Site	Santa Rosa	California
United States	Regeneron Investigational Site	Seattle	Washington
United States	Regeneron Investigational Site	Tampa	Florida
United States	Regeneron Investigational Site	Tulsa	Oklahoma
United States	Regeneron Investigational Site	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Investigator's Global Assessment (IGA) 0 or 1 (and Reduction From Baseline of =2 Points) at Week 16	IGA is an assessment scale used to determine severity of atopic dermatitis (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 was an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA "0" or "1" and a reduction from baseline of =2 points at Week 16 were reported. [Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered non-responder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).]	Baseline and Week 16
Primary	Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (=75% Improvement From Baseline) at Week 16	The EASI score was used to measure the severity and extent of 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 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI--75 responders were the participants who achieved =75% overall improvement in EASI score from baseline to Week 16. [Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered nonresponder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).]	Baseline and Week 16
Secondary	Percent Change From Baseline in EASI Score at Week 16	The Eczema Area and Severity Index (EASI) score was used to measure the severity and extent of 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 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. [Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.]	Baseline and Week 16
Secondary	Percent Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score at Week 16	Peak Pruritus NRS is an assessment tool used by subjects to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3) /3. [Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]	Baseline and Week 16
Secondary	Percentage of Participants With Improvement (Reduction =3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16	Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, participants achieving a reduction of =3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]	Baseline to Week 16
Secondary	Percentage of Participants With Improvement (Reduction =4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16	Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, participants achieving a reduction of =4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]	Baseline to Week 16
Secondary	Percentage of Participants With EASI-50 (=50% Improvement From Baseline) at Week 16	The EASI score was used to measure the severity and extent of AD and measured 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 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved =50% overall improvement in EASI score at Week 16. [Values after first rescue treatment used were set to missing. Participants with missing value at Week 16 were considered as a non-responder].	Baseline and Week 16
Secondary	Percentage of Participants With EASI-90 (=90% Improvement From Baseline) at Week 16	The EASI score was used to measure the severity and extent of AD and measured 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 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-90 responders were the participants who achieved =90% overall improvement in EASI score at Week 16. [Values after first rescue treatment used were set to missing. Participants with missing value at week 16 were considered as a non-responder.]	Baeline and Week 16
Secondary	Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction =3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline	Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, participants achieving a reduction of =3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]	Baseline up to week 16
Secondary	Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction =4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline	Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" [For this endpoint, subjects achieving a reduction of =4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.]	Baseline up to Week 16
Secondary	Change From Baseline in Percent Body Surface Area (BSA) at Week 16	BSA 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.	Baseline and Week 16
Secondary	Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16	The SCORAD index is a clinical tool for assessing the severity of atopic dermatitis. 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).	Baseline and Week 16
Secondary	Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Total Score at Week 16	The CDLQI is a 10-item questionnaire used to measure how much a participant's skin problem had affected the participant's quality of life (QOL) over a recall period of the past week. The questionnaire consists of 10 items. For each item the scale is rated as follows: 0 = Not at all = Not relevant; 1 = Only a little; 2 = Quite a lot; 3 = Very much = Yes = Prevents school. The CDLQI total score is the sum of the score of each question with a maximum of 30 and a minimum of 0. The higher the score, the greater the impact is on the QOL.	Baseline and Week 16
Secondary	Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16	The POEM is a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults with atopic eczema. The format is subject response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on symptom frequency during the past week (ie, 0 = 'no days', 1 = '1 to 2 days', 2 = '3 to 4 days', 3 = '5 to 6' days, and 4 = 'every day'). The total score is the sum of the 7 items which is ranged from 0 to 28; a high score is indicative of a poor quality of life (QOL).	Baseline and Week 16
Secondary	Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 16	Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Particpants were asked the following question for maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.	Baseline and Week 16
Secondary	Percent Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 4	Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question for maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.	Baseline and Week 4
Secondary	Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) at Week 16	The HADS is 14-item questionnaire with two subscales: anxiety & depression. Each item is rated on a 4-point scale (0-3). A person could score between 0 & 21 for each subscale (anxiety & depression). A high score is indicative of a poor state. Scores of 11 or more on either subscale are considered a 'definite case' of psychological morbidity, while scores of 8 to 10 represents 'probable case' & 0 to 7 'not a case'. The total score was the sum of the 2 sub-scores; therefore, the full range of possible values for the reported data is 0-42.	Baseline and Week 16
Secondary	Percentage of Participants With Improvement (Reduction =4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline at Week 4	Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question for maximum itch intensity: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours?" For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.	Baseline and Week 4
Secondary	Percentage of Participants With Skin-infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Through Week 16	Any untoward medical occurrence in a subject who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study (Week 16)). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.	Baseline through Week 16
Secondary	Percentage of Participants With Serious TEAEs Through Week 16	Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study (Week 28)). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.	Baseline through Week 16