Dermatitis, Atopic
Conditions
Brief summary
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.
Interventions
DRUGBI 655130
Solution for infusion
DRUGPlacebo
Solution for infusion
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in the Eczema Area and Severity Index (EASI) Score at Week 16 | Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Eczema Area and Severity Index (EASI) at Week 4 | Baseline (day 1) and Week 4 (day 29 ±3 days), up to 32 days. | 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. |
| Percentage Change From Baseline in Eczema Area and Severity Index (EASI) at Week 4 | Baseline (day 1) and Week 4 (day 29 ±3 days), up to 32 days. | 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. |
| Proportion of Patients With a 50% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI50) at Week 4 and 16 | Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days. | 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. |
| Number of Patients With Drug Related Adverse Events (AEs) | Up to 28 weeks, see endpoint description for more details. | 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. |
| Change From Baseline in SCORing of Atopic Dermatitis (SCORAD) at Week 4 | Baseline (day 1) and Week 4 (day 29 ±3 days), up to 32 days. | 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. |
| Change From Baseline in SCORing of Atopic Dermatitis (SCORAD) at Week 16 | Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days. | 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. |
| 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 | 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. 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. |
| Proportion of Patients With a 75% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI75) at Week 4 and 16 | 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. 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. |
Countries
Canada, Japan, United States
Participant flow
Recruitment details
This was a phase IIa multicentre, randomized, double-blind, placebocontrolled, study to evaluate the safety, tolerability and efficacy of treatment with BI 655130 in adult patients with moderate to severe atopic dermatitis.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Intravenous Every 4 Weeks Placebo intravenous (i.v.) infusion once every 4 weeks (q4w) during the double blind period from week 0 to 16 (4 treatments in total). At week 16 patients were assessed based on their Eczema Area and Severity Index (EASI) score, patients with EASI≥75 were classified as responders and patients with EASI\<75 were classified as non-responders. Responders received no further treatment, non-responders were offered an open label treatment with 600 mg Spesolimab (BI 655130) i.v. infusion once every 4 weeks from week 16 to 28 (4 treatments in total, last dose at week 28). End of study was at week 44. | 18 |
| Spesolimab 600 mg Intravenous Every 4 Weeks 600 milligram (mg) Spesolimab (BI 655130) intravenous (i.v.) infusion once every 4 weeks (q4w) during the double blind period from week 0 to 16 (4 treatments in total). At week 16 patients were assessed based on their Eczema Area and Severity Index (EASI) score, patients with EASI≥75 were classified as responders and patients with EASI\<75 were classified as non-responders. Responders received no further treatment, non-responders were offered an open label treatment with 600 mg Spesolimab (BI 655130) i.v. infusion once every 4 weeks from week 16 to 28 (4 treatments in total, last dose at week 28). End of study was at week 44. | 33 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 - Double Blind Period | Adverse Event | 3 | 5 |
| Period 1 - Double Blind Period | Lack of Efficacy | 2 | 1 |
| Period 1 - Double Blind Period | Lost to Follow-up | 1 | 1 |
| Period 1 - Double Blind Period | Protocol Violation | 1 | 1 |
| Period 1 - Double Blind Period | Withdrawal by Subject | 3 | 3 |
| Period 2 - Open Label Period | Adverse Event | 0 | 3 |
| Period 2 - Open Label Period | Lost to Follow-up | 1 | 0 |
| Re-allocation | Not re-allocated to open label period | 2 | 6 |
Baseline characteristics
| Characteristic | Total | Spesolimab 600 mg Intravenous Every 4 Weeks | Placebo Intravenous Every 4 Weeks |
|---|---|---|---|
| Age, Continuous | 39.4 years STANDARD_DEVIATION 15.5 | 43.2 years STANDARD_DEVIATION 15.9 | 32.4 years STANDARD_DEVIATION 12.4 |
| Eczema Area and Severity Index (EASI) Score | 26.50 Score on a scale STANDARD_DEVIATION 9.49 | 26.53 Score on a scale STANDARD_DEVIATION 10.07 | 26.43 Score on a scale STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 27 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Investigator's Global Assessment (IGA) score | 3.3 Score on a scale STANDARD_DEVIATION 0.5 | 3.2 Score on a scale STANDARD_DEVIATION 0.4 | 3.4 Score on a scale STANDARD_DEVIATION 0.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 10 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 17 Participants | 7 Participants |
| SCORing of Atopic Dermatitis (SCORAD) | 61.06 Score on a scale STANDARD_DEVIATION 11.76 | 60.09 Score on a scale STANDARD_DEVIATION 10.36 | 62.82 Score on a scale STANDARD_DEVIATION 14.13 |
| Sex: Female, Male Female | 26 Participants | 15 Participants | 11 Participants |
| Sex: Female, Male Male | 25 Participants | 18 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 33 | 0 / 22 |
| other Total, other adverse events | 10 / 18 | 16 / 33 | 6 / 22 |
| serious Total, serious adverse events | 1 / 18 | 3 / 33 | 3 / 22 |
Outcome results
Primary
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.
Time frame: Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days.
Population: Full Analysis Set (FAS): All participants who were randomised, received at least one dose during the trial, and had a baseline measurement for the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Intravenous Every 4 Weeks | Percentage Change From Baseline in the Eczema Area and Severity Index (EASI) Score at Week 16 | -12.3 Percent change | Standard Error 14.3 |
| Spesolimab 600 mg Intravenous Every 4 Weeks | Percentage Change From Baseline in the Eczema Area and Severity Index (EASI) Score at Week 16 | -37.9 Percent change | Standard Error 9.8 |
p-value: 0.149290% CI: [-54.9, 3.7]Mixed Models Analysis
Secondary
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.
Time frame: Baseline (day 1) and Week 4 (day 29 ±3 days), up to 32 days.
Population: Full Analysis Set (FAS): All participants who were randomised, received at least one dose during the trial, and had a baseline measurement for the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Intravenous Every 4 Weeks | Absolute Change From Baseline in Eczema Area and Severity Index (EASI) at Week 4 | -7.0 Change in score on a scale | Standard Error 3 |
| Spesolimab 600 mg Intravenous Every 4 Weeks | Absolute Change From Baseline in Eczema Area and Severity Index (EASI) at Week 4 | -6.3 Change in score on a scale | Standard Error 2.2 |
p-value: 0.861390% CI: [-5.7, 7]Mixed Models Analysis
Secondary
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.
Time frame: Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days.
Population: Full Analysis Set (FAS): All participants who were randomised, received at least one dose during the trial, and had a baseline measurement for the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Intravenous Every 4 Weeks | Change From Baseline in SCORing of Atopic Dermatitis (SCORAD) at Week 16 | -10.7 Change in score on a scale | Standard Error 10 |
| Spesolimab 600 mg Intravenous Every 4 Weeks | Change From Baseline in SCORing of Atopic Dermatitis (SCORAD) at Week 16 | -25.5 Change in score on a scale | Standard Error 6.8 |
p-value: 0.226690% CI: [-35.2, 5.5]Mixed Models Analysis
Secondary
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.
Time frame: Baseline (day 1) and Week 4 (day 29 ±3 days), up to 32 days.
Population: Full Analysis Set (FAS): All participants who were randomised, received at least one dose during the trial, and had a baseline measurement for the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Intravenous Every 4 Weeks | Change From Baseline in SCORing of Atopic Dermatitis (SCORAD) at Week 4 | -13.3 Change in score on a scale | Standard Error 7 |
| Spesolimab 600 mg Intravenous Every 4 Weeks | Change From Baseline in SCORing of Atopic Dermatitis (SCORAD) at Week 4 | -13.2 Change in score on a scale | Standard Error 5.2 |
p-value: 0.9990% CI: [-14.6, 14.8]Mixed Models Analysis
Secondary
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.
Time frame: Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days.
Population: Full Analysis Set (FAS): All participants who were randomised, received at least one dose during the trial, and had a baseline measurement for the primary endpoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo Intravenous Every 4 Weeks | 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 | Week 4 | 1 Participants |
| Placebo Intravenous Every 4 Weeks | 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 | Week 16 | 0 Participants |
| Spesolimab 600 mg Intravenous Every 4 Weeks | 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 | Week 4 | 2 Participants |
| Spesolimab 600 mg Intravenous Every 4 Weeks | 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 | Week 16 | 3 Participants |
Comparison: Risk difference at week 490% CI: [-0.159, 0.12]
Comparison: Risk difference at week 1690% CI: [-0.05, 0.207]
Secondary
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.
Time frame: Up to 28 weeks, see endpoint description for more details.
Population: Double blind period: Safety Analysis Set (SAF): patients who were randomised, and received at least one dose during the trial.~Re-allocation treatment period: This patient set includes all randomized patients who received at least one dose of study drug and received study medication after re-allocation visit (i.e., after Week 16 visit).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Intravenous Every 4 Weeks | Number of Patients With Drug Related Adverse Events (AEs) | Double blind treatment period | 6 Participants |
| Placebo Intravenous Every 4 Weeks | Number of Patients With Drug Related Adverse Events (AEs) | Re-allocation treatment period | 0 Participants |
| Spesolimab 600 mg Intravenous Every 4 Weeks | Number of Patients With Drug Related Adverse Events (AEs) | Double blind treatment period | 4 Participants |
| Spesolimab 600 mg Intravenous Every 4 Weeks | Number of Patients With Drug Related Adverse Events (AEs) | Re-allocation treatment period | 2 Participants |
Secondary
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.
Time frame: Baseline (day 1) and Week 4 (day 29 ±3 days), up to 32 days.
Population: Full Analysis Set (FAS): All participants who were randomised, received at least one dose during the trial, and had a baseline measurement for the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Intravenous Every 4 Weeks | Percentage Change From Baseline in Eczema Area and Severity Index (EASI) at Week 4 | -21.6 Percent change | Standard Error 11.3 |
| Spesolimab 600 mg Intravenous Every 4 Weeks | Percentage Change From Baseline in Eczema Area and Severity Index (EASI) at Week 4 | -23.8 Percent change | Standard Error 8.3 |
p-value: 0.875490% CI: [-25.8, 21.4]Mixed Models Analysis
Secondary
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.
Time frame: Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days.
Population: Full Analysis Set (FAS): All participants who were randomised, received at least one dose during the trial, and had a baseline measurement for the primary endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Intravenous Every 4 Weeks | Proportion of Patients With a 50% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI50) at Week 4 and 16 | Week 4 | 0.333 Proportion of patients |
| Placebo Intravenous Every 4 Weeks | Proportion of Patients With a 50% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI50) at Week 4 and 16 | Week 16 | 0.056 Proportion of patients |
| Spesolimab 600 mg Intravenous Every 4 Weeks | Proportion of Patients With a 50% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI50) at Week 4 and 16 | Week 4 | 0.303 Proportion of patients |
| Spesolimab 600 mg Intravenous Every 4 Weeks | Proportion of Patients With a 50% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI50) at Week 4 and 16 | Week 16 | 0.303 Proportion of patients |
Comparison: Risk difference at week 490% CI: [-0.254, 0.176]
Comparison: Risk difference at week 1690% CI: [0.053, 0.396]
Secondary
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.
Time frame: Baseline (day 1) and Week 16 (day 113 ±3 days), up to 116 days.
Population: Full Analysis Set (FAS): All participants who were randomised, received at least one dose during the trial, and had a baseline measurement for the primary endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Intravenous Every 4 Weeks | Proportion of Patients With a 75% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI75) at Week 4 and 16 | Week 4 | 0.111 Proportion of patients |
| Placebo Intravenous Every 4 Weeks | Proportion of Patients With a 75% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI75) at Week 4 and 16 | Week 16 | 0.056 Proportion of patients |
| Spesolimab 600 mg Intravenous Every 4 Weeks | Proportion of Patients With a 75% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI75) at Week 4 and 16 | Week 4 | 0.091 Proportion of patients |
| Spesolimab 600 mg Intravenous Every 4 Weeks | Proportion of Patients With a 75% Improvement From Baseline in Eczema Area and Severity Index (EASI)(EASI75) at Week 4 and 16 | Week 16 | 0.152 Proportion of patients |
Comparison: Risk difference at week 490% CI: [-0.204, 0.117]
Comparison: Risk difference at week 1690% CI: [-0.08, 0.232]