A Randomized, Double-Blind, Placebo-Controlled Study to Demonstrate the Efficacy and Long-Term Safety of Dupilumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 740
- Primary Endpoint
- Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 16
Study Overview
Brief Summary
The primary objective of the study was to demonstrate the efficacy of Dupilumab administered concomitantly with topical corticosteroid (TCS) through Week 16 in adult participants with moderate-to-severe atopic dermatitis (AD) compared to placebo administered concomitantly with TCS.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Chronic AD that had been present for at least 3 years before the screening visit;
- •Documented recent history (within 6 months before the screening visit) of inadequate response to a sufficient course of out-patient treatment with topical AD medication(s).
Exclusion Criteria
- •Participation in a prior Dupilumab clinical trial;
- •Important side effects of topical medication (e.g. intolerance to treatment, hypersensitivity reactions, significant skin atrophy, systemic effects), as assessed by the investigator or treating physician;
- •Having used any of the following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, was likely to require such treatment(s) during the first 2 weeks of study treatment:
- •Immunosuppressive/immunomodulating drugs (e.g, systemic steroids, cyclosporine, mycophenolate-mofetil, Janus kinase inhibitors, interferon-gamma [IFN-γ], azathioprine, methotrexate, etc.);
- •Phototherapy for AD;
- •Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit;
- •History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening;
- •Positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody at the screening visit;
- •Active or acute infection requiring systemic treatment within 2 weeks before baseline visit;
- •Known or suspected history of immunosuppression;
- •Pregnant or breastfeeding women, or planning to become pregnant or breastfeed during the participant's participation in this study.
- •Note: The eligibility criteria listed above is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial therefore not all inclusion/ exclusion criteria are listed.
Arms & Interventions
Placebo qw
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection weekly (qw) from Week 1 to Week 51.
Intervention: Placebo (for Dupilumab) (Drug)
Placebo qw
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection weekly (qw) from Week 1 to Week 51.
Intervention: Topical Corticosteroid (TCS) (Other)
Dupilumab 300 mg q2w
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab every 2 weeks (q2w) from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Intervention: Dupilumab (Drug)
Dupilumab 300 mg q2w
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab every 2 weeks (q2w) from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Intervention: Placebo (for Dupilumab) (Drug)
Dupilumab 300 mg q2w
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab every 2 weeks (q2w) from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.
Intervention: Topical Corticosteroid (TCS) (Other)
Dupilumab 300 mg qw
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Intervention: Dupilumab (Drug)
Dupilumab 300 mg qw
Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 51.
Intervention: Topical Corticosteroid (TCS) (Other)
Outcomes
Primary Outcomes
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 16
Time Frame: Baseline to Week 16
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). Participants with IGA score "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported.
Secondary Outcomes
- Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52(Baseline to Week 52)
- Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 52(Baseline to Week 52)
- Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 52(Baseline to Week 52)
- Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16(Baseline to Week 16)
- Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16(Baseline to Week 16)
- Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16(Baseline to Week 16)
- Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16(Baseline to Week 16)
- Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 52(Baseline to Week 52)
- Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4(Baseline to Week 4)
- Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52(Baseline to Week 52)
- Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 2(Baseline to Week 2)
- Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16(Baseline to Week 16)
- Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 24(Baseline to Week 24)
- Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2(Baseline to Week 2)
- Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16(Baseline to Week 16)
- Percent Change From Baseline in Total Global Individual Signs Score (GISS) to Week 16(Baseline to Week 16)
- Proportion of Topical Atopic Dermatitis Medication-Free Days Through Week 52(Baseline to Week 52)
- Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 52(Baseline to Week 52)
- Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 52(Baseline to Week 52)
- Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16(Baseline to Week 16)
- Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 16(Baseline to Week 16)
- Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16(Baseline to Week 16)
- Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16(Baseline to Week 16)
- Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16(Baseline to Week 16)
- Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 52(Baseline to Week 52)
- Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 52(Baseline to Week 52)
- Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 52(Baseline to Week 52)
- Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 52(Baseline to Week 52)
- Number of Flares Through Week 52(Baseline up to Week 52)
- Number of Serious Treatment Emergent Adverse Events (TEAEs) Leading to Study Drug Discontinuation Through Week 52(Baseline up to Week 52)
- Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Week 52(Baseline up to Week 52)
- Number of Skin Infection TEAEs (Excluding Herpetic Infections) From Baseline Through Week 52(Baseline up to Week 52)
- Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52(Baseline up to Week 52)
- Number of Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52(Baseline up to Week 52)