To Assess the Safety and Activity of GBR 830, Compared to Placebo, in Adults With Moderate-to-severe Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of GBR 830 on biomarkers in atopic dermatitis to enable further studies in this indication.

Official Title
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A Phase IIa, Double-Blind, Randomised, Placebo-controlled, Exploratory Study to Evaluate the Safety, Biological Activity and Pharmacokinetics of GBR 830 in Adults With Moderate-to-Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Biological: GBR 830
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years or older Atopic dermatitis involvement that of at least 10% body surface area Exclusion Criteria: Treatment with systemic corticosteroids within 4 weeks before randomization, and topical steroids, tacrolimus and/or pimecrolimus within 1 week before the randomization (except emollients, and mild steroids (class 6 or 7) Any cell-depleting agents including but not limited to rituximab: within 6 months prior to the baseline visit or until lymphocyte and CD 19+ lymphocyte counts return to normal, whichever is longer. Other biologics: within 5 half-lives or 8 weeks prior to the baseline visit, whichever is longer. Allergen immunotherapy within 6 months before the baseline visit. Patient with history of serious local infection and systemic infection Patient with history or current evidence of diseases such as tuberculosis, malignant disease, other inflammatory or autoimmune disease or HIV or Hepatitis B or C positive.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GBR 830<br>Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart. | Biological: GBR 830<br> <br> |
| Placebo Comparator: Placebo<br>Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart. | Biological: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | A treatment-emergent adverse event (TEAE) was defined as any new adverse event (AEs) or worsening of an existing condition after administration of the study drug up to and including the follow-up visit. | 16 weeks | 
| Change From Baseline in Thickness of Lesional Skin Biopsies | Epidermal thickness was assessed in Hematoxylin and Eosin stained sections of lesional skin biopsies on Day 1 (baseline), Day 29, and Day 71. | Day 1, before dosing (baseline), and Day 29 and Day 71, after dosing. | 
| Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies | Ratio of post-baseline/baseline value of messenger ribonucleic acid (mRNA) expression in lesional skin biopsies is reported. | 71 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Eczema Area and Severity Index (EASI) Clinical Scores From Baseline | In EASI, four disease characteristics of atopic dermatitis (erythema, edema/papulation, excoriation, and lichenification) are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the four body regions (Head and neck, trunk, arms, and legs). The assigned percentages of body surface area (BSA) for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs, respectively. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin in that area: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD. | Day 4, Day 29, Day 57, Day 71 | 
| Percentage of Participants Who Achieved an Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 | The IGA is an assessment scale used in clinical studies to determine severity of AD based on a 5-point scale ranging from 0 (clear) to 4 (severe/very severe). | Day 4, Day 29, Day 57, Day 71 | 
| Pharmacokinetics of GBR 830 in Terms of Cmax After First and Second Dose. | Pharmacokinetics in terms of Cmax (maximum observed concentration after second [last] dosing interval) was estimated after the first and second dose. | Blood samples were collected on Day 1 and Day 29: pre-dose (15 mins), end of infusion (1 hour) and 1.5, 2, 72, and 504 hours post start of infusion | 
| Pharmacokinetics of GBR 830 in Terms of AUC0-tau After the First and Second Dose. | Pharmacokinetics in terms of AUC0-tau [Trapezoid calculation of area under the serum drug concentration-time curve from time zero (pre dose time point of the infusion) to the end of the dosing interval] was estimated. | Blood samples were collected on Day 1 and Day 29: pre-dose (15 mins), end of infusion (1 hour) and 1.5, 2, 72, and 504 hours post start of infusion | 
| Number of Participants Positive or Negative for Anti-drug Antibodies (ADA) to GBR 830 to Evaluate Immunogenicity | Blood samples were collected at time points to detect anti-drug antibodies (ADAs) to GBR 830, as per procedures similar to collection of PK samples. Antibodies of GBR 830 were detected and confirmed using a validated enzyme-linked immunosorbent assay (ELISA) method. | Samples collected for immunogenicity analysis at Baseline (pre-dose), and at Day 15, Day 29 (pre-dose), Day 57, and Day 85. |