A Long-term Study of Baricitinib (LY3009104) With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis That Are Not Controlled With Cyclosporine or for Those Who Cannot Take Oral Cyclosporine Because it is Not Medically Advisable

Phase 3

Completed

• Conditions: Atopic Dermatitis
• Interventions: Drug: Baricitinib; Drug: Placebo; Drug: Topical corticosteroid

• Registration Number: NCT03428100
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The purpose of this study is to determine the efficacy and safety of baricitinib in combination with topical corticosteroids in participants with moderate to severe atopic dermatitis who have experienced failure to cyclosporine or are intolerant to, or have contraindication to cyclosporine.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-02-05
• Study First Submitted QC: 2018-02-05
• Study First Posted: 2018-02-09
• Study Start: 2018-05-15
• Primary Completion: 2019-11-25
• Results First Submitted: 2020-11-26
• Results First Submitted QC: 2021-01-15
• Results First Posted: 2021-01-19
• Study Completion: 2023-04-20
• Status Verified: 2024-04-15
• Last Update Submitted: 2024-04-18
• Last Update Posted: 2024-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 463

Inclusion Criteria

• Have been diagnosed with moderate to severe Atopic Eczema (Atopic Dermatitis) for at least 12 months.
• Have had inadequate response to existing topical (applied to the skin) medications within 6 months preceding screening.
• Are willing to discontinue certain treatments for eczema (such as systemic and topical treatments during a washout period).
• Agree to use emollients daily.
• Have a medical contraindication to cyclosporine, or had intolerance and/or unacceptable toxicity or inadequate response to cyclosporine in the past.

Exclusion Criteria

• Are currently experiencing or have a history of other concomitant skin conditions (e.g., psoriasis or lupus erythematosus), or a history of erythrodermic, refractory, or unstable skin disease that requires frequent hospitalizations and/or intravenous treatment for skin infections.

• A history of eczema herpeticum within 12 months, and/or a history of 2 or more episodes of eczema herpeticum in the past.

• Participants who are currently experiencing a skin infection that requires treatment, or are currently being treated, with topical or systemic antibiotics.

• Have any serious illness that is anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring (e.g., unstable chronic asthma).

• Have been treated with the following therapies:

  • Monoclonal antibody for less than 5 half-lives prior to randomization.
  • Received prior treatment with any oral Janus kinase (JAK) inhibitor less than 4 weeks prior to randomization.
  • Received oral corticosteroids within 4 weeks prior to randomization or parenteral corticosteroids administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization or are anticipated to require parenteral injection of corticosteroids during the study.
  • Have had an intra-articular corticosteroid injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization.

• Have high blood pressure characterized by a repeated systolic blood pressure >160 millimeters of mercury (mm Hg) or diastolic blood pressure >100 mm Hg.

• Have had major surgery within the past eight weeks or are planning major surgery during the study.

• Have experienced any of the following within 12 weeks of screening: venous thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.

• Have a history of recurrent (≥ 2) VTE or are considered at high risk of VTE as deemed by the investigator.

• Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, lymphoproliferative disease or neuropsychiatric disorders or any other serious and/or unstable illness.

• Have a current or recent and/or clinically serious viral, bacterial, fungal, or parasitic infection including but not limited to herpes zoster, tuberculosis.

• Have specific laboratory abnormalities related to thyroid, renal and liver function, or blood cells.

• Have received certain treatments that are contraindicated.

• Pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2 mg Baricitinib	Placebo	2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
2 mg Baricitinib	Topical corticosteroid	2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
Placebo	Placebo	Placebo administered orally once daily in combination with topical corticosteroids. Additional Placebo administered orally to maintain the blind.
LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders)	Placebo	2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib (Responders/Partial Responders)	Placebo	2 mg Baricitinib rerandomized to 1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib (Responders/Partial Responders)	Topical corticosteroid	2 mg Baricitinib rerandomized to 1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
4 mg Baricitinib	Baricitinib	4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
4 mg Baricitinib	Placebo	4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
4 mg Baricitinib	Topical corticosteroid	4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
1 mg Baricitinib	Topical corticosteroid	1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
Placebo	Topical corticosteroid	Placebo administered orally once daily in combination with topical corticosteroids. Additional Placebo administered orally to maintain the blind.
LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders)	Topical corticosteroid	2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
1 mg Baricitinib	Placebo	1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
Long Term Extension(LTE) Substudy 4mg Baricitinib to 4mg Baricitinib (Responders/Partial Responders)	Placebo	4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
Long Term Extension(LTE) Substudy 4mg Baricitinib to 4mg Baricitinib (Responders/Partial Responders)	Topical corticosteroid	4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 4 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy	Topical corticosteroid	4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy	Placebo	2 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy	Placebo	1 mg administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Placebo	2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Topical corticosteroid	2 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Placebo	1 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Topical corticosteroid	1 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Placebo to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Placebo	Placebo rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders)	Placebo	4 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders)	Topical corticosteroid	4 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy	Topical corticosteroid	2 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Placebo (Responders/Partial Responders) - Did Not Enter Substudy	Placebo	Placebo administered orally once daily (continued previous dose) in combination with topical corticosteroids. Additional placebo administered orally to maintain the blind.
LTE Placebo to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Placebo	Placebo rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy	Topical corticosteroid	1 mg administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Placebo (Responders/Partial Responders) - Did Not Enter Substudy	Topical corticosteroid	Placebo administered orally once daily (continued previous dose) in combination with topical corticosteroids. Additional placebo administered orally to maintain the blind.
LTE 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Placebo	4 mg administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Placebo	2 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Placebo	1 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 4 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy	Placebo	4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Baricitinib	4 mg administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Topical corticosteroid	4 mg administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Topical corticosteroid	1 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Baricitinib	2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Topical corticosteroid	2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Baricitinib	1 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Placebo to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Topical corticosteroid	Placebo rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Placebo to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Topical corticosteroid	Placebo rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
1 mg Baricitinib	Baricitinib	1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
2 mg Baricitinib	Baricitinib	2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
Long Term Extension(LTE) Substudy 4mg Baricitinib to 4mg Baricitinib (Responders/Partial Responders)	Baricitinib	4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders)	Baricitinib	4 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders)	Baricitinib	2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib (Responders/Partial Responders)	Baricitinib	2 mg Baricitinib rerandomized to 1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 4 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy	Baricitinib	4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy	Baricitinib	2 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy	Baricitinib	1 mg administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Baricitinib	2 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Baricitinib	1 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Placebo to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Baricitinib	Placebo rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.
LTE Placebo to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy	Baricitinib	Placebo rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (Placebo, 2 mg or 4 mg Baricitinib)	Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving EASI75 (Placebo, 1 mg Baricitinib)	Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.; Missing values were imputed using Non-Responder Imputation (NRI), where non-responders were participants who permanently discontinue, are rescued, or are without at least 1 post-baseline observation.
Percentage of Participants Achieving EASI90	Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 (no disease) to 72 (severe disease). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score.
Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement	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 Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)	Week 16	The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.
Percent Change From Baseline in EASI Score	Baseline, Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 (no disease) to 72 (severe disease).; Least Squares Mean (LSM) were calculated using mixed model repeated measures (MMRM) model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline score and baseline score-by-visit-interaction as fixed continuous effects.
Percentage of Participants Achieving IGA of 0 or 1 With a >=2-point Improvement	Week 24	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 Achieving EASI50	Week 16	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 (no disease) to 72 (severe disease). The EASI50 is defined as a ≥ 50% improvement from baseline in the EASI score.
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment	Week 16	Percentage of participants developing skin infections requiring antibiotic treatment.
Mean Number of Days Without Topical Corticosteroids (TCS) Use	Week 16	The ANCOVA model includes treatment, region, and baseline disease severity (IGA) as factors.
Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)	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 a visual analogue scales (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.; The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.
Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)	Baseline, Week 16	The ADSS is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep due to itch, frequency of waking due to itch, and difficulty getting back to sleep last night due to itch. Item 2 frequency of waking last night is reported by selecting the number of times they woke up each night, ranging from 0 to 29 times, where the higher a number indicates a worse outcome. The ADSS is designed to be completed daily, using a daily diary, with respondents thinking about sleep "last night." Each item is scored individually.; LS Mean were calculated using an MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in Skin Pain NRS	Baseline, Week 16	Skin Pain NRS is a participant-administered,11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Overall severity of a participant's skin pain is indicated by selecting the number, using a daily diary, that best describes the worst level of skin pain in the past 24 hours.; LS Mean were calculated using MMRM model includes treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Percentage of Participants Achieving EASI75	Week 52	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.
Percentage of Participants Achieving IGA of 0	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 Achieving SCORAD90	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 a visual analogue scales (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. The SCORAD90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the SCORAD score.
Change From Baseline in SCORAD	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 were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in Body Surface Area (BSA) Affected	Baseline, Week 16	The BSA affected by AD will be assessed for 4 separate body regions and is collected as part of the EASI assessment: 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. The overall total percentage will be reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1\*BSAhead and neck + 0.3\*BSAtrunk + 0.2\* BSAupper limbs + 0.4\*BSAlower limbs.; LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline on the Hospital Anxiety Depression Scale (HADS)	Baseline, Week 16	The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 item questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.'; LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in the Dermatology Life Quality Index (DLQI)	Baseline, Week 16	The DLQI is a simple, participant-administered,10 question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The recall period of this scale is over the last "week." Response categories include "not at all," "a little," "a lot," and "very much," with corresponding scores of 0, 1, 2, and 3, respectively, and unanswered or "not relevant" responses scored as "0." Scores range from 0 to 30 ("no impact on participant's life" to "extremely large effect on participant's life"), and a 4-point change from baseline is considered as the minimal clinically important difference threshold.; LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Mean Gram Quantity of Low and Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights)	Week 16	Average weights of full tubes were used to determine the dispensed weights for each region. Returned tubes were weighed with cap without carton to determine the amount of TCS in grams (g) used at each visit. Analysis was done via analysis of variance (ANOVA), with geographic region, baseline disease severity, and treatment as factors in the model.
Percent Change From Baseline in Itch NRS	Baseline, Week 16	The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.; LS Means were calculated using MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.
Percent Change From Baseline in Itch NRS at Week 24	Baseline, Week 24	The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.; LS Means were calculated using MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.
Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)	Baseline, Week 16	The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life.; LS Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by visit-interactions as fixed continuous effects.
Change From Baseline in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm	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 Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline in the Patient Global Impression of Severity - Atopic Dermatitis (PGI-S-AD) Score	Baseline, Week 16	The PGI-S-AD is a single-item question asking the participant how they would rate their overall AD symptoms over the past 24 hours, using a daily diary. The 5 categories of responses are "(0) no symptoms", "(1) very mild", "(2) mild" "(3) moderate", and "(4) severe."; LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire	Baseline, Week 16	The WPAI-AD participant questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. The WPAI-AD consists of 6 items grouped in 4 domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment, that range from 0% to 100%, with higher values indicating greater impairment.; LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)	Baseline, Week 16	EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (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 Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interactions as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)	Week 68	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 Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)	Week 104	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 Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)	Week 68	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.
Percentage of Participants With a Response of IGA 0 or 1 Assessed at Week 104 - Participants Not Entered Into Substudy (All Participants)	Week 104	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. All missing values were imputed using mLOCF.
Time to Retreatment (Time to IGA ≥3) Randomized Downtitration (All Patients Entering the Substudy)	Week 52 Up to Week 200	Participants who entered the Substudy and relapsed with an IGA ≥3.
Percent Change From Baseline in Itch NRS at Week 52	Baseline, Week 52	The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.; LS Means were calculated using MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.
Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)	Week 68	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. All missing values were imputed using modified last observation carried forward (mLOCF).
Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)	Week 104	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.
Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)	Week 68	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. All missing values were imputed using modified last observation carried forward (mLOCF).
Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)	Week 104	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. All missing values were imputed using mLOCF.
Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at Week 68 Participants Not Entered Into Substudy (All Participants)	Week 68	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. All missing values were imputed using mLOCF.
Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)	Week 104	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. All missing values were imputed using modified last observation carried forward (mLOCF).
Percentage of Participants With a Response of IGA 0 or 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)	Week 68	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. All missing values were imputed using mLOCF.
Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at Week 104 Participants Not Entered Into Substudy (All Participants)	Week 104	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. All missing values were imputed using mLOCF.
Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)	Week 104	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. All missing values were imputed using mLOCF.
Percentage of Participants With a Response of IGA 0 or 1 Assessed at Week 68 - Participants Not Entered Into Substudy (All Participants)	Week 68	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. All missing values were imputed using mLOCF.
Percentage of Participants With A Response of EASI75 Assessed at Week 68 - Participants Not Entered Into Substudy (All Participants)	Week 68	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.
Percentage of Participants With A Response of EASI75 Assessed at Week 104 - Participants Not Entered Into Substudy (All Participants)	Week 104	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 (no disease) to 72 (severe disease). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.

Trial Locations

Locations (103)

Universitätsklinikum Graz; 🇦🇹 Graz, Steiermark, Austria

Universitätsklinik Innsbruck; 🇦🇹 Innsbruck, Tyrol, Austria

KA Rudolfstiftung; 🇦🇹 Wien, Austria

AKH; 🇦🇹 Wien, Austria

Sozialmed. Zentrum Ost - Donauspital; 🇦🇹 Wien, Austria

Cliniques Universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

Universitair Ziekenhuis Brussel; 🇧🇪 Brussel, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

UZ Leuven - Campus Sint-Rafaël; 🇧🇪 Leuven, Belgium

Cedoes Centro Diagnostico Pequisa Osteoporose E Santo Ltd; 🇧🇷 Vitoria, ES, Brazil

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