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Study to Determine the Safety and Effectiveness of Dupilumab for Treatment of Atopic Dermatitis (AD)

Phase 2
Completed
Conditions
Atopic Dermatitis (AD)
Interventions
Drug: Placebo
Drug: Dupilumab
Other: Background treatment
Registration Number
NCT01979016
Lead Sponsor
Regeneron Pharmaceuticals
Brief Summary

The primary objective of the study was to assess the efficacy of Dupilumab, compared to placebo, in adult patients with moderate-to-severe atopic dermatitis (AD).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
54
Inclusion Criteria
  1. Male or female, 18 years or older;
  2. Chronic AD that had been present for at least 3 years before the screening visit;
  3. Patients with documented recent history (within 6 months before the screening visit) of inadequate response to out-patient treatment with topical medications, or for whom topical treatments were otherwise inadvisable;
  4. Willing and able to comply with all clinic visits and study-related procedures.
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Exclusion Criteria
  1. Prior participation in a Dupilumab clinical trial;

  2. Treatment with an investigational drug within 8 weeks or within 5 half-lives before the baseline visit;

  3. The following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, will likely require such treatment(s) during the first 4 weeks of study treatment:

    • Systemic corticosteroids;
    • Immunosuppressive/immunomodulating drugs;
    • Phototherapy for AD;
  4. Treatment with topical corticosteroids, tacrolimus and/or pimecrolimus within 1 week before the baseline visit;

  5. Treatment with certain biologics;

  6. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks before the baseline visit;

  7. Planned major surgical procedure during the participant's participation in this study;

  8. Participant was a member of the investigational team or his/her immediate family;

  9. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit

  10. Pregnant or breast-feeding women or women planning to become pregnant or breastfeed during the study;

Note: The information 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.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo qwPlaceboTwo subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection once weekly (qw) from Week 1 to Week 15.
Placebo qwBackground treatmentTwo subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection once weekly (qw) from Week 1 to Week 15.
Dupilumab 200 mg qwDupilumabTwo subcutaneous injections of Dupilumab 200 milligram (mg) (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Dupilumab 200 mg qwBackground treatmentTwo subcutaneous injections of Dupilumab 200 milligram (mg) (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15.
Primary Outcome Measures
NameTimeMethod
Percent Change From Baseline in the Eczema Area Severity Index Score (EASI) to Week 16Baseline to Week 16

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) 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 medication use were set to missing and missing values imputed by last observation carried forward (LOCF).

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" at Week 16Week 16

IGA was 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 was an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were considered as non-responders.

Percentage of Participants Who Achieved IGA Score Reduction From Baseline of ≥2 Points at Week 16Baseline to Week 16

IGA was 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. Participants with reduction in IGA score from baseline of ≥2 points at Week 16 were reported. Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were treated as non-responders.

Absolute Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16Baseline to Week 16

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

Percent Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16Baseline to Week 16

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

Absolute Change From Baseline in EASI Score to Week 16Baseline to 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. Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16Baseline to Week 16

SCORAD was 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.) were assessed and scored. Total score ranged from 0 (absent disease) to 103 (severe disease). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16Baseline to Week 16

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). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16Baseline to Week 16

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 ranged from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50, EASI-75 and EASI-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% respectively, overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.

Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16Baseline to Week 16

SCORAD was 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.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). SCORAD-50, SCORAD-75 and SCORAD-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% respectively, overall improvement in SCORAD score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing SCORAD score at Week 16 were counted as non-responders.

Absolute Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16Baseline to Week 16

POEM was a 7-item questionnaire that assessed disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Percent Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16Baseline to Week 16

POEM was a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16Baseline to Week 16

Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

Changes From Baseline in GISS Cumulative Score to Week 16Baseline to Week 16

Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).Values after first rescue medication use were set to missing and missing values were imputed by LOCF.

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