A Study in Patients With Atopic Eczema to Test How Effective BI 655130 is and How Well it is Tolerated

Study Overview
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Brief Summary
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The primary objective of this trial is to investigate the safety, tolerability and efficacy of BI 655130 in patients with Atopic Dermatitis (AD) following repeated intravenous administrations compared to placebo.

Official Title
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Phase IIa, Multicentre, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Safety, Tolerability and Efficacy of Treatment With BI 655130 in Adult Patients With Moderate to Severe Atopic Dermatitis

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Drug: BI 655130
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated written informed consent in accordance with Good Clinical Practice (GCP) and local legislation prior to the start of any screening procedures Male or female patients, 18 to 75 years of age at screening Diagnosis of atopic dermatitis for at least 1 year Moderate to severe atopic dermatitis defined as: At least 10% Body Surface Area (BSA) of atopic dermatitis involvement at screening and baseline Eczema Area and Severity Index (EASI) of at least 12 at screening and at least 16 at baseline Investigator Global Assessment (IGA) of at least 3 at screening and baseline Documented history of inadequate response to topical corticosteroid as judged by the investigator Willing to use a standard emollient for the duration of the study Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. Exclusion Criteria: Use of topical corticosteroids or other agents for atopic dermatitis within 7 days prior to first dose of trial treatment. Use of systemic corticosteroids or other agents for atopic dermatitis within 4 weeks prior to first dose of trial treatment. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Women who stop nursing before the study drug administration do not need to be excluded from participating; they should refrain from breastfeeding up to 16 weeks after the last study drug administration Patient with a transplanted organ (with exception of a corneal transplant > 12 weeks prior to screening) or who have ever received stem cell therapy (e.g., Prochymal). Any documented active or suspected malignancy or history of malignancy within 5 years prior to the screening visit, except appropriately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix. Use of any restricted medication or any drug considered likely to interfere with the safe conduct of the study, as assessed by the investigator. History of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients. Active systemic infections (Fungal and bacterial disease) during the last 2 weeks prior to first drug administration, per investigator assessment. Relevant chronic or acute infections (exception: common cold) including human immunodeficiency virus (HIV) or viral hepatitis. A patient can be re-screened if the patient was treated and is cured from the acute infection. Active or Latent Tuberculosis (TB): Patients with active tuberculosis are excluded. Patients with a positive QuantiFERON TB test during screening are excluded, unless: Patient had previous diagnosis of active or latent TB and has completed appropriate treatment per local practice/guidelines within the last 3 years and at least 6 months before first administration of trial medication under this protocol (patients may be re-screened once to meet this criterion) Patients with suspected false positive or indeterminate QuantiFERON TB result may be re-tested once If the QuantiFERON TB test result is not available or provides indeterminate results after repeat testing: A tuberculin skin test reaction ≥10mm (≥5mm if receiving ≥15mg/d prednisone or its equivalent) is considered positive. Currently enrolled in another investigational device or drug trial, or less than 30 days or 5 half lives, whichever is longer since ending another investigational device or drug trial(s), or receiving other investigational treatment(s). Evidence of a current or previous disease, medical condition (including chronic alcohol or drug abuse or any condition) other than AD, surgical procedure, psychiatric or social problems, medical examination finding (including vital signs and ECG), or laboratory value at the screening outside the reference range that in the opinion of the investigator is clinically significant and would make the study participant unreliable to adhere to the protocol, comply with all study visits/procedures or to complete the trial, compromise the safety of the patient or compromise the quality of the data. Major surgery (major according to the investigator) performed within 12 weeks prior to first study drug adminstration or planned during the study (e.g. hip replacement, aneurysm removal, stomach ligation). Severe, progressive, or uncontrolled hepatic disease, defined as >3-fold Upper Limit of Normal (ULN) elevation in AST or ALT or alkaline phosphatase, or >2-fold ULN elevation in total bilirubin.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spesolimab<br>i.v. | Drug: BI 655130<br>* Solution for infusion<br>* Other names: Spesolimab;|
| Placebo Comparator: Placebo<br>i.v. | Drug: Placebo<br>* Solution for infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in the Eczema Area and Severity Index (EASI) Score at Week 16 | Percentage change from baseline in the Eczema Area and Severity Index (EASI) Score at Week 16. The EASI score assesses the extent of disease at four body sites and measures four clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale of zero to three. The EASI score confers a maximum of 72 and evaluates two dimensions of Atopic Dermatitis (AD): disease extent and clinical signs. The suggested severity strata for the EASI are as follows: 0 = clear; 0.1-1.0 = almost clear; 1.1-7.0 = mild; 7.1-21.0 = moderate; 21.1-50.0 = severe; 50.1-72.0 = very severe. Restricted maximum likelihood(REML)-based Mixed Model Repeated Measures (MMRM) including fixed, categorical effects of treatment, visit, and Asian/Non-Asian (yes/no) as well as the treatment-by-visit interaction, and continuous, fixed covariates of baseline endpoint and baseline-by-visit interaction. Unstructured covariance matrix was used. | Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Drug Related Adverse Events (AEs) | Number of patients with drug related Adverse Events (AEs) reported separately in both for the double blind period as well as the re-allocation treatment period. Double blind period: Baseline (week 1) to the last study drug administration date (week 12) + Residual effects period (REP, 16 weeks). For patients who initiated the re-allocation treatment period the REP was shortened to the date of first re-allocation treatment period treatment administration. Up to a total time frame of 28 weeks. Re-allocation treatment period: Week 1 of re-allocation treatment period to the last study drug administration date (week 12 of re-allocation treatment period) + REP (16 weeks), or end-of-study date, whichever occurred earlier. Up to a total time frame of 28 weeks. | Up to 28 weeks, see endpoint description for more details. | 
| Absolute Change From Baseline in Eczema Area and Severity Index (EASI) at Week 4 | Absolute change from baseline in the Eczema Area and Severity Index (EASI) Score at Week 4. The EASI score assesses the extent of disease at four body sites and measures four clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale of zero to three. The EASI score confers a maximum of 72 and evaluates two dimensions of Atopic Dermatitis (AD): disease extent and clinical signs. The suggested severity strata for the EASI are as follows: 0 = clear; 0.1-1.0 = almost clear; 1.1-7.0 = mild; 7.1-21.0 = moderate; 21.1-50.0 = severe; 50.1-72.0 = very severe. Restricted maximum likelihood(REML)-based Mixed Model Repeated Measures (MMRM) including fixed, categorical effects of treatment, visit, and Asian/Non-Asian (yes/no) as well as the treatment-by-visit interaction, and continuous, fixed covariates of baseline endpoint and baseline-by-visit interaction. Unstructured covariance matrix was used. | Baseline (day 1) and Week 4 (day 29 ±3 days), up to 32 days. | 
| Percentage Change From Baseline in Eczema Area and Severity Index (EASI) at Week 4 | Percentage change from baseline in the Eczema Area and Severity Index (EASI) Score at Week 4. The EASI score assesses the extent of disease at four body sites and measures four clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale of zero to three. The EASI score confers a maximum of 72 and evaluates two dimensions of Atopic Dermatitis (AD): disease extent and clinical signs. The suggested severity strata for the EASI are as follows: 0 = clear; 0.1-1.0 = almost clear; 1.1-7.0 = mild; 7.1-21.0 = moderate; 21.1-50.0 = severe; 50.1-72.0 = very severe. Restricted maximum likelihood(REML)-based Mixed Model Repeated Measures (MMRM) including fixed, categorical effects of treatment, visit, and Asian/Non-Asian (yes/no) as well as the treatment-by-visit interaction, and continuous, fixed covariates of baseline endpoint and baseline-by-visit interaction. Unstructured covariance matrix was used. | Baseline (day 1) and Week 4 (day 29 ±3 days), up to 32 days. | 
| Proportion of Patients With a 50% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI50) at Week 4 and 16 | Proportion of patients with a 50% improvement from baseline in Eczema Area and Severity Index (EASI)(EASI50) at Week 4 and 16. The EASI score assesses the extent of disease at four body sites and measures four clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale of zero to three. The EASI score confers a maximum of 72 and evaluates two dimensions of Atopic Dermatitis (AD): disease extent and clinical signs. The suggested severity strata for the EASI are as follows: 0 = clear; 0.1-1.0 = almost clear; 1.1-7.0 = mild; 7.1-21.0 = moderate; 21.1-50.0 = severe; 50.1-72.0 = very severe. | Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days. | 
| Proportion of Patients With a 75% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI75) at Week 4 and 16 | Proportion of patients with a 75% improvement from baseline in Eczema Area and Severity Index (EASI)(EASI75) at Week 4 and 16. The EASI score assesses the extent of disease at four body sites and measures four clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale of zero to three. The EASI score confers a maximum of 72 and evaluates two dimensions of Atopic Dermatitis (AD): disease extent and clinical signs. The suggested severity strata for the EASI are as follows: 0 = clear; 0.1-1.0 = almost clear; 1.1-7.0 = mild; 7.1-21.0 = moderate; 21.1-50.0 = severe; 50.1-72.0 = very severe. | Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days. | 
| Change From Baseline in SCORing of Atopic Dermatitis (SCORAD) at Week 4 | SCORing of Atopic Dermatitis (SCORAD). Extent (A): rule of 9 was used to calculate body surface area affected by AD. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed from none=0to severe=3. Severity scores summed to B (0-18). Subjective symptoms (C): pruritus and sleep, each of these 2 were scored by participant/caregiver using visual analogue scale from 0 to 10, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7*B/2 + C; range from 0 to 103; higher values of SCORAD=worse outcome. REML-based MMRM including fixed, categorical effects of treatment, visit, and Asian/Non-Asian as well as the treatment-by-visit interaction, and continuous, fixed covariates of baseline endpoint and baseline-by-visit interaction. Unstructured covariance matrix was used. | Baseline (day 1) and Week 4 (day 29 ±3 days), up to 32 days. | 
| Change From Baseline in SCORing of Atopic Dermatitis (SCORAD) at Week 16 | SCORing of Atopic Dermatitis (SCORAD). Extent (A): rule of 9 was used to calculate body surface area affected by AD. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed from none=0to severe=3. Severity scores summed to B (0-18). Subjective symptoms (C): pruritus and sleep, each of these 2 were scored by participant/caregiver using visual analogue scale from 0 to 10, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7*B/2 + C; range from 0 to 103; higher values of SCORAD=worse outcome. REML-based MMRM including fixed, categorical effects of treatment, visit, and Asian/Non-Asian as well as the treatment-by-visit interaction, and continuous, fixed covariates of baseline endpoint and baseline-by-visit interaction. Unstructured covariance matrix was used. | Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days. | 
| Number of Patients Achieving at Least a 2-grade Reduction From Baseline to Clear (0) or Almost Clear (1) in Investigator's Global Assessment (IGA) at Week 4 and 16 | Number of patients achieving at least a 2-grade reduction from baseline to clear (0) or almost clear (1) in Investigator's Global Assessment (IGA) at Week 4 and 16. IGA score allows investigators to assess the overall disease severity at one given time point. It is a 5-point scale with: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe. The overall IGA score includes the assessment of erythema, induration/papulation, lichenification, and oozing/crusting. For the first three sections the following scale will be used: None, Barely Perceptible (Minimal for lichenification), Slight but Definite, Clearly Perceptible or Marked. For oozing/crusting the available answers are None or Present. | Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days. |