A Study in Patients With Atopic Eczema to Test How Effective BI 655130 is and How Well it is Tolerated
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Spesolimab i.v. |
Drug: BI 655130
Solution for infusion
Other Names:
|
| Placebo Comparator: Placebo i.v. |
Drug: Placebo
Solution for infusion
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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) in both the double blind period as well as the open label period. Double blind period: Baseline to the last study drug administration date + REP (16 weeks). For patients who initiated the open label treatment the REP was shortened to the date of first open label treatment administration. Up to a total time frame of 28 weeks. Open label period: Week 16 to the last study drug administration date + REP (16 weeks), or end-of-study date, whichever occurred earlier. Up to a total time frame of 28 weeks (up to Week 44).
- 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.
- 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.
- 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."
Eligibility Criteria
Criteria
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:
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At least 10% Body Surface Area (BSA) of atopic dermatitis involvement at screening and baseline
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Eczema Area and Severity Index (EASI) of at least 12 at screening and at least 16 at baseline
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Investigator Global Assessment (IGA) of at least 3 at screening and baseline
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Documented history of inadequate response to topical corticosteroid as judged by the investigator
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Willing to use a standard emollient for the duration of the study
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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:
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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.
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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).
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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.
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Use of any restricted medication or any drug considered likely to interfere with the safe conduct of the study, as assessed by the investigator.
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History of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients.
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Active systemic infections (Fungal and bacterial disease) during the last 2 weeks prior to first drug administration, per investigator assessment.
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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.
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Active or Latent Tuberculosis (TB):
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Patients with active tuberculosis are excluded.
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Patients with a positive QuantiFERON TB test during screening are excluded, unless:
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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)
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Patients with suspected false positive or indeterminate QuantiFERON TB result may be re-tested once
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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.
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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).
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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.
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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).
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Center for Dermatology and Plastic Surgery | Scottsdale | Arizona | United States | 85260 |
| 2 | Clinical Physiology Associates | Fort Myers | Florida | United States | 33912 |
| 3 | Finlay Medical Research Corp | Miami | Florida | United States | 33126 |
| 4 | University of South Florida | Tampa | Florida | United States | 33612 |
| 5 | ForCare Clinical Research, Inc. | Tampa | Florida | United States | 33613 |
| 6 | The Indiana Clinical Trials Center, PC | Plainfield | Indiana | United States | 46168 |
| 7 | Unity Clinical Research | Oklahoma City | Oklahoma | United States | 73118 |
| 8 | Dermatology Treatment and Research Center, PA | Dallas | Texas | United States | 75230 |
| 9 | Progressive Clinical Research | San Antonio | Texas | United States | 78213 |
| 10 | Center for Clinical Studies | Webster | Texas | United States | 77598 |
| 11 | University of Alberta Hospital (University of Alberta) | Edmonton | Alberta | Canada | T6G 2B7 |
| 12 | NewLab Clinical Research Inc. | St. John's | Newfoundland and Labrador | Canada | A1C 2H5 |
| 13 | Innovaderm Research Inc. | Montreal | Quebec | Canada | H2X 2V1 |
| 14 | Aichi Medical University Hospital | Aichi, Nagakute | Japan | 480-1195 | |
| 15 | National Hospital Organization Kyushu Medical Center | Fukuoka, Fukuoka | Japan | 810-8563 | |
| 16 | Kurume University Hospital | Fukuoka, Kurume | Japan | 830-0011 | |
| 17 | Hosui General Medical Clinic | Hokkaido, Sapporo | Japan | 064-0807 | |
| 18 | Tennocho Ekimae Dermatology and Allergology | Kanagawa, Yokohama | Japan | 240-0004 | |
| 19 | University Hospital Kyoto Prefectural University of Medicine | Kyoto, Kyoto | Japan | 602-8566 | |
| 20 | Nagasaki University Hospital | Nagasaki, Nagasaki | Japan | 852-8501 | |
| 21 | Osaka City University Hospital | Osaka, Osaka | Japan | 545- 8586 | |
| 22 | Tokyo Medical University Hachioji Medical Center | Tokyo, Hachioji | Japan | 193-0998 | |
| 23 | Showa University Hospital | Tokyo, Shinagawa-ku | Japan | 142-8666 |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 1368-0032