Evaluation of the Efficacy and Safety of Lebrikizumab (LY3650150) in Moderate to Severe Atopic Dermatitis (ADvocate1)

Phase 3

Completed

• Conditions: Atopic Dermatitis
• Interventions: Biological: Lebrikizumab; Other: Placebo

• Registration Number: NCT04146363
• Lead Sponsor: Eli Lilly and Company

Brief Summary

This is a randomized, double-blind, placebo-controlled, parallel-group study which is 52 weeks in duration. The study is designed to confirm the safety and efficacy of lebrikizumab as monotherapy for treatment of moderate-to-severe atopic dermatitis utilizing a 16-week induction treatment period and a 36-week long-term maintenance treatment period.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study Start: 2019-09-24
• Study First Submitted: 2019-10-29
• Study First Submitted QC: 2019-10-30
• Study First Posted: 2019-10-31
• Primary Completion: 2021-06-21
• Study Completion: 2022-05-03
• Results First Submitted: 2022-06-20
• Results First Submitted QC: 2022-08-04
• Results First Posted: 2022-08-29
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-02
• Last Update Posted: 2022-11-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 424

Inclusion Criteria

• Male or female adults and adolescents (≥12 years and ≥40 kg)
• Chronic atopic dermatitis (according to American Academy of Dermatology Consensus Criteria) that has been present for ≥1 year before the screening visit
• Eczema Area and Severity Index (EASI) score ≥16 at the baseline visit
• Investigator Global Assessment (IGA) score ≥3 (scale of 0 to 4) at the baseline visit
• ≥10% body surface area (BSA) of atopic dermatitis involvement at the baseline visit
• History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable

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Exclusion Criteria

• Prior treatment with dupilumab or tralokinumab

• Treatment with topical corticosteroids, calcineurin inhibitors or phosphodiesterase-4 inhibitors such as crisaborole within 1 week prior to the baseline visit

• Treatment with any of the following agents within 4 weeks prior to the baseline visit:

  • Immunosuppressive/immunomodulating drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.)
  • Phototherapy and photochemotherapy (PUVA) for AD

• Treatment with the following prior to the baseline visit:

  • An investigational drug within 8 weeks or within 5 half-lives (if known) of baseline, whichever is longer
  • Cell-depleting biologics, including to rituximab, within 6 months of baseline
  • Other biologics within 5 half-lives (if known) or 16 weeks of baseline, whichever is longer

• Treatment with a live (attenuated) vaccine within 12 weeks of the baseline visit or planned during the study

• Uncontrolled chronic disease that might require bursts of oral corticosteroids, e.g., co-morbid severe uncontrolled asthma

• Evidence of active acute or chronic hepatitis

• History of human immunodeficiency virus (HIV) infection or positive HIV serology

• History of malignancy, including mycosis fungoides, within 5 years before the screening visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin

• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lebrikizumab 250 Q2W	Placebo	Induction Period (Baseline-Week 16): 500 milligram (mg) Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 visits followed by a single 250 mg Lebrikizumab injection Q2W from Week 4 until Week 14. Maintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection Q2W until Week 50. For participants who received placebo in the Induction Period, the maintenance loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two 250 mg Lebrikizumab SC injections on Week 18. To maintain the blind, for participants who received Lebrikizumab in the Induction Period, the maintenance loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 18.
Escape Arm (Lebrikizumab Q2W)	Placebo	Maintenance Period (Week 16-Week 52): Blinded loading doses based on prior treatment assignment will be administered, followed by one 250 mg Lebrikizumab SC injection Q2W until Week 50 in an open-label fashion. For participants who received placebo in the Induction Period, the loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two 250 mg Lebrikizumab SC injections on Week 18. To maintain the loading dose blind, for participants who received Lebrikizumab in the Induction Period, the loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 18. For participants who do not maintain an acceptable response during the Maintenance Period and entered the Escape Arm, the loading doses will be administrated at entry and 2 weeks after entry based on the treatment assignment prior to entering escape arm.
Placebo	Placebo	Induction Period (Baseline-Week 16): Two subcutaneous (SC) injections of Placebo as a loading dose at Baseline and Week 2 followed by a single injection every 2 weeks (Q2W) from Week 4 until Week 14. Maintenance Period (Week 16-Week 52): Two placebo SC injections as loading dose on Week 16 and Week 18. One placebo SC injection Q2W until Week 50.
Lebrikizumab 250 Q2W	Lebrikizumab	Induction Period (Baseline-Week 16): 500 milligram (mg) Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 visits followed by a single 250 mg Lebrikizumab injection Q2W from Week 4 until Week 14. Maintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection Q2W until Week 50. For participants who received placebo in the Induction Period, the maintenance loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two 250 mg Lebrikizumab SC injections on Week 18. To maintain the blind, for participants who received Lebrikizumab in the Induction Period, the maintenance loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 18.
Lebrikizumab 250 Q4W	Placebo	Maintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection every 4 weeks (Q4W) on Weeks 20, 24, 28, 32, 36, 40, 44, and 48. One placebo SC injection Q4W on Weeks 22, 26, 30, 34, 38, 42, 46, and 50. For participants who received placebo in the Induction Period, the maintenance loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two placebo injections on Week 18. To maintain the blind, for participants who received Lebrikizumab in the Induction Period, the maintenance loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. Two placebo injections on Week 18
Escape Arm (Lebrikizumab Q2W)	Lebrikizumab	Maintenance Period (Week 16-Week 52): Blinded loading doses based on prior treatment assignment will be administered, followed by one 250 mg Lebrikizumab SC injection Q2W until Week 50 in an open-label fashion. For participants who received placebo in the Induction Period, the loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two 250 mg Lebrikizumab SC injections on Week 18. To maintain the loading dose blind, for participants who received Lebrikizumab in the Induction Period, the loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 18. For participants who do not maintain an acceptable response during the Maintenance Period and entered the Escape Arm, the loading doses will be administrated at entry and 2 weeks after entry based on the treatment assignment prior to entering escape arm.
Lebrikizumab 250 Q4W	Lebrikizumab	Maintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection every 4 weeks (Q4W) on Weeks 20, 24, 28, 32, 36, 40, 44, and 48. One placebo SC injection Q4W on Weeks 22, 26, 30, 34, 38, 42, 46, and 50. For participants who received placebo in the Induction Period, the maintenance loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two placebo injections on Week 18. To maintain the blind, for participants who received Lebrikizumab in the Induction Period, the maintenance loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. Two placebo injections on Week 18

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16	Baseline to Week 16	The IGA measures the investigator's global assessment of the participant's overall severity of their Atopic Dermatitis (AD), based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16	Baseline to Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI-75 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe).; The EASI-75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4	Baseline to Week 4	The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 in Adults	Baseline to Week 16	The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2	Baseline to Week 2	The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16	Baseline to Week 16	The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life.
Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline at Week 16	Baseline to Week 16	Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale \[0 (not at all) to 4 (unable to sleep at all)\]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary.
Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1	Baseline to Week 1	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Percentage of Participants From Those With a Pruritus NRS of ≥4-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52	Baseline to Week 52	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16	Baseline to Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe).; The EASI-90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the EASI score.
Percentage of Participants With a Pruritus NRS Score of ≥5-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16	Baseline to Week 16	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2	Baseline to Week 2	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Percent Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16	Baseline, Week 16	The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), \& subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease.; LS Mean was calculated using the ANCOVA model with treatment group and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Percent Change in EASI Score From Baseline to Week 16	Baseline, Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe).; LS Mean was calculated using ANCOVA model with treatment, stratification factors of geographic region, age group, baseline IGA score (IGA 3 versus 4) as fixed factors baseline value as covariate.
Percentage of Participants Achieving EASI-90 From Baseline to Week 4	Baseline to Week 4	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe).; The EASI-90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the EASI score.
Percent Change in Sleep-loss Score From Baseline to Week 16	Baseline, Week 16	Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale \[0 (not at all) to 4 (unable to sleep at all)\]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4	Baseline to Week 4	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Pharmacokinetics (PK): Average Serum Concentration of Lebrikizumab at Week 52	Predose: Baseline, Week 4, Week 16, Week 32, Week 52	PK: Average serum concentration of lebrikizumab at the Week 52 trough timepoint. Serum concentration is a combined measure obtained from Baseline, Week 4, Week 16, Week 32, Week 52 and average measure was reported at week 52.
Percent Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16	Baseline, Week 16	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." Least Squares (LS) Mean was calculated using analysis of covariance (ANCOVA) model with treatment and randomization strata (region, disease severity, age) as fixed factors and baseline value as covariate.
Percentage of Participants With a Pruritus NRS Score of ≥4-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16	Baseline to Week 16	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16	Baseline, Week 16	The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life.; LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Percentage of Participants Achieving ≥4 Point Improvement in DLQI From Baseline to Week 16	Baseline to Week 16	The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life.
Change From Baseline in Sleep-loss Score at Week 16	Baseline, Week 16	Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale \[0 (not at all) to 4 (unable to sleep at all)\]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1	Baseline to Week 1	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2	Baseline to Week 2	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4	Baseline to Week 4	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Percentage of Participants From Those Re-randomized Having Achieved IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 16 Who Continue to Exhibit and IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 52	Baseline to Week 52	The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Change From Baseline in Percent Body Surface Area (BSA) at Week 16	Baseline, Week 16	The BSA affected by AD will be assessed for 4 separate body regions: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. BSA was calculated using the participant's palm using the 1% rule, 1 palm was equivalent to 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 palms for head and neck (10%), 20 palms for upper extremities (20%), 30 palms for trunk, including axilla and groin (30%), 40 palms for lower extremities, including buttocks (40%). Percent of BSA for a body region was calculated as = total number of palms in a body region \* % surface area equivalent to 1 palm. Overall percent BSA of all 4 body regions ranges from 0% to 100 % with higher values representing greater severity of AD.
Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index	Baseline, Week 16	The EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state.; LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16 - Adolescents	Baseline, Week 16	PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Percent Change in SCORAD (Having Achieved EASI-75 at Week 16) From Baseline at Week 52	Baseline, Week 52	The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), \& subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. LS mean was calculated using ANCOVA model with treatment group, baseline value, and stratification factors geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS)	Baseline, Week 16	The EQ-5D-5L is a 2-part measurement. The second part is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Change From Baseline in PROMIS Depression at Week 16 - Adults	Baseline, Week 16	PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. The PROMIS measures will be completed by the participant in the study clinic. PROMIS depression has 8 questions on Emotion Distress-Depression (or Pediatric Depressive Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater depression. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Percentage of Participants From Those Re-randomized Having Achieved EASI-75 at Week 16 Who Continued to Exhibit EASI-75 at Week 52 (EASI-75 Calculated Relative to Baseline EASI Score)	Baseline to Week 52	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI-75 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe).; The EASI-75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score.
Percentage of Participants From Those With a Pruritus NRS of ≥5-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52	Baseline to Week 52	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Change From Baseline in PROMIS Depression at Week 16 - Adolescents	Baseline, Week 16	PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS depression has 8 questions on Emotion Distress-Depression (or Pediatric Depressive Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater depression. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-Reported Comorbid Asthma	Baseline, Week 16	The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/ limitation) scale. The ACQ-5 score is the average of the individual item scores and ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicate lower asthma control.; LS Mean was calculated using ANCOVA with treatment, geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16	Baseline, Week 16	POEM is a 7-item, validated, questionnaire used by the participant to assess disease symptoms over the last week. The participant is asked to respond to 7 questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding and weeping. All 7 answers carry equal weight with a total possible score from 0 to 28 (answers scored as: No days=0; 1# 2 days = 1; 3-4 days = 2; 5#6 days = 3; everyday = 4). A high score is indicative of a poor quality of life. POEM responses will be captured using an electronic diary and transferred into the clinical database. LS Mean was calculated using MMRM model using treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit as covariates, geographic region, age group, baseline IGA (3 versus 4) score as fixed.
Change From Baseline in PROMIS Anxiety at Week 16 - Adults	Baseline, Week 16	PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. The PROMIS measures will be completed by the participant in the study clinic. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-Scores (mean = 50 and a standard deviation = 10) with higher scores representing greater anxiety. LS Mean was calculated using the ANCOVA model with treatment and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors and baseline value as covariate.
Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16 - Adolescents	Baseline, Week 16	The CDLQI questionnaire is designed for use in children (4 to 16 years of age). It consists of 10 items that are grouped into 6 domains: symptoms \& feelings, leisure, school or holidays, personal relationships, sleep, \& treatment. The scoring of each question is: Very much =3; Quite a lot = 2; Only a little = 1; Not at all = 0. CDLQI total score is calculated by summing all 10 items responses and has a range of 0 to 30 (higher scores are indicative of greater impairment).; LS Mean was calculated using MMRM model which includes treatment, baseline value, visit, the interaction of the baseline value-by-visit as covariates, the interaction of treatment by-visit, geographic region, age group, and baseline IGA (3 versus 4) score as fixed factors.

Trial Locations

Locations (94)

Latvian Dermatology Institute; 🇱🇻 Riga, Latvia

JSC "CD8 Alergology Clinic"; 🇱🇹 Kaunas, Lithuania

Sant Joan de Deu Serveis En Salut Mental; 🇪🇸 SANT BOI DE Llobrega, Barcelona, Spain

Twoja Przychodnia - Szczecinskie Centrum Medyczne; 🇵🇱 Szczecin, West Pomeranian, Poland

Wallace Medical Group, Inc.; 🇺🇸 Beverly Hills, California, United States

Johnson Dermatology; 🇺🇸 Fort Smith, Arkansas, United States

California Dermatology & Clinical Research Institute; 🇺🇸 Encinitas, California, United States

Belle Aimee Skincare Clinic; 🇺🇸 Fountain Valley, California, United States

Dermatology Research Associates; 🇺🇸 Los Angeles, California, United States

Lynn Health Science Institute; 🇺🇸 Oklahoma City, Oklahoma, United States

ACRC Studies; 🇺🇸 San Diego, California, United States

Central Connecticut Dermatology; 🇺🇸 Cromwell, Connecticut, United States

St. Francis Medical Institute; 🇺🇸 Clearwater, Florida, United States

Community Research Foundation Inc; 🇺🇸 Miami, Florida, United States

IACT Health - VHC; 🇺🇸 Columbus, Georgia, United States

The Indiana Clinical Trials Center; 🇺🇸 Plainfield, Indiana, United States

Skin Sciences, PLLC; 🇺🇸 Louisville, Kentucky, United States

MediSearch Clinical Trials; 🇺🇸 Saint Joseph, Missouri, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

St Joseph Dermatology and Vein Clinic; 🇺🇸 Saint Joseph, Michigan, United States

JDR Dermatology Research; 🇺🇸 Las Vegas, Nevada, United States

ALLCUTIS Research; 🇺🇸 Portsmouth, New Hampshire, United States

Icahn Sch of Med at Mt. Sinai; 🇺🇸 New York, New York, United States

Wake Research Associates; 🇺🇸 Raleigh, North Carolina, United States

Sadick Research Group; 🇺🇸 New York, New York, United States

Clinical Research Institute; 🇺🇸 Medford, Oregon, United States

Vital Prospects Clinical Research Institute, P.C.; 🇺🇸 Tulsa, Oklahoma, United States

Clinical Partners, LLC; 🇺🇸 Johnston, Rhode Island, United States

Bellaire Dermatology; 🇺🇸 Bellaire, Texas, United States

Progressive Clinical Research; 🇺🇸 San Antonio, Texas, United States

Premier Clinical Research; 🇺🇸 Spokane, Washington, United States

The St. George Hospital; 🇦🇺 Kogarah, New South Wales, Australia

Holdsworth House Medical Practice; 🇦🇺 Sydney, New South Wales, Australia

Skin & Cancer Foundation Australia; 🇦🇺 Westmead, New South Wales, Australia

The Skin Centre; 🇦🇺 Benowa, Queensland, Australia

Emeritus Research; 🇦🇺 Camberwell, Victoria, Australia

Eastern Clinical Research Unit; 🇦🇺 Box Hill, Victoria, Australia

Skin Health Institute Inc.; 🇦🇺 Carlton, Victoria, Australia

Sinclair Dermatology; 🇦🇺 East Melbourne, Victoria, Australia

Fremantle Dermatology; 🇦🇺 Fremantle, Western Australia, Australia

Burswood Dermatology; 🇦🇺 Victoria Park, Western Australia, Australia

CARe Clinic; 🇨🇦 Red Deer, Alberta, Canada

CCA Medical Research; 🇨🇦 Ajax, Ontario, Canada

Skin Health; 🇨🇦 Cobourg, Ontario, Canada

The Centre for Dermatology; 🇨🇦 Richmond Hill, Ontario, Canada

Kliiniliste uuringute Keskus OU; 🇪🇪 Tartu, Estonia

CHU DIJON - Hopital le Bocage; 🇫🇷 Dijon Cedex, France

Hopital Larrey; 🇫🇷 Toulouse cedex 9, France

Korea University Ansan Hospital; 🇰🇷 Ansan-si, Gyeonggi-do, Korea, Republic of

Pusan National University Hospital; 🇰🇷 Pusan, Korea, Korea, Republic of

Hanyang University Medical Center; 🇰🇷 Seoul, Korea, Korea, Republic of

Ajou University Hospital; 🇰🇷 Suwon-si, Kyung Gi-Do, Korea, Korea, Republic of

Ulsan University Hospital; 🇰🇷 Ulsan, Korea, Korea, Republic of

Soon Chun Hyang University Seoul Hospital; 🇰🇷 Seoul, Yongsan-gu, Korea, Republic of

Incheon St. Mary's Hospital; 🇰🇷 Incheon, Korea, Republic of

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Konkuk University Medical Center; 🇰🇷 Seoul, Korea, Republic of

Chungang University Hospital; 🇰🇷 Seoul, Korea, Republic of

Hallym University Kangnam Sacred Heart Hospital; 🇰🇷 Seoul, Korea, Republic of

Clinic of Dermatology and STD; 🇱🇻 Riga, Latvia

Health Center 4, Affiliate Diagnostic Center; 🇱🇻 Riga, Latvia

Health and Aesthetics LTD; 🇱🇻 Riga, Latvia

Smite Aija - Practice in Dermatology Venereology; 🇱🇻 Talsi, Latvia

Hospital of Lithuanian University of Health Sciences Kauno klinikos; 🇱🇹 Kaunas, Lithuania

Jsc Renmeda; 🇱🇹 Vilnius, Lithuania

JSC "Center for Diagnosis and Treatment of Allergic Diseases"; 🇱🇹 Vilnius, Lithuania

Inlita (Santaros CTC); 🇱🇹 Vilnius, Lithuania

Vilnius University Hospital Santaros klinikos; 🇱🇹 Vilnius, Lithuania

Diamond Clinic; 🇵🇱 Krakow, Malopolskie, Poland

Alergo-Med Specjalistyczna Przychodnia Lekarska Sp Z O.O.; 🇵🇱 Tarnow, Malopolska, Poland

Centrum Medyczne Angelius Provita; 🇵🇱 Katowice, Slaskie, Poland

GynCentrum Sp z o.o.; 🇵🇱 Katowice, Poland

Specjalistyczny Osrodek Alergologiczno-Internistyczny ALL-ME; 🇵🇱 Krakow, Poland

Samodzielny Publiczny Szpital Kliniczny nr 1; 🇵🇱 Lublin, Poland

Centrum Alergologii Teresa Hofman; 🇵🇱 Poznan, Poland

CityClinic Przychodnia Lekarsko-Psychologiczna; 🇵🇱 Wroclaw, Poland

Hospital De Basurto; 🇪🇸 Bilbao, Vizcaya, Spain

Hospital General Universitario Alicante; 🇪🇸 Alicante, Spain

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Infanta Leonor; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen Macarena; 🇪🇸 Sevilla, Spain

Hopital Saint-Louis; 🇫🇷 Paris, Cedex 10, France

CHU de Bordeaux Hopital Saint Andre; 🇫🇷 Bordeaux Cedex, France

Cabinet Médical; 🇫🇷 Martigues, France

Oregon Medical Research Center; 🇺🇸 Portland, Oregon, United States

ForCare Clinical Research; 🇺🇸 Tampa, Florida, United States

Dermatology and Dermatologic Surgery; 🇨🇦 Ottawa, Ontario, Canada

Veracity Clinical Research Pty Ltd; 🇦🇺 Woolloongabba, Queensland, Australia

Beacon Clinical Research, LLC; 🇺🇸 Quincy, Massachusetts, United States

Children's Hospital, Affiliate of Vilnius University Hospital Santaros klinikos; 🇱🇹 Vilnius, Lithuania

Centralny Szpital Kliniczny MSWiA; 🇵🇱 Warszawa, Mazowieckie, Poland

Zespol Naukowo - Leczniczy "Iwolang" Sp. z o.o.; 🇵🇱 Iwonicz Zdroj, Wojewodztwo Podkarpackie, Poland

Clinical Research Group Sp. z o.o.; 🇵🇱 Warszawa, Poland