Clinical Effect, Safety and Tolerability of GSK1070806 in Atopic Dermatitis

Study Overview
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Brief Summary
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This study will evaluate efficacy and safety of GSK1070806 in moderate to severe atopic dermatitis (AtD) participants.

Official Title
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A Phase Ib, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study of the Clinical Effect, Safety and Tolerability of a Single Intravenous Infusion of GSK1070806 in Moderate to Severe Atopic Dermatitis Patients

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Drug: GSK1070806
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Moderate to severe AtD (confirmed by a dermatologist) according to the Hannifin and Rajka criteria or Eichenfield revised criteria. Onset of AtD symptoms occurring at least 6 months prior to Screening, with stable disease for at least 1 month prior to Screening. Eczema Activity Severity Index greater than or equal to (>=)16; Investigator Global Assessment score >=3. Group 1- Biologic Naïve: Topical First Line Treatment: Documented recent history (within 6 months before Screening) of: a) either an inadequate response (IR) to out-patient treatment with at least one topical treatment (intermittent topical corticosteroid, topical calcineurin inhibitor), topical inhibitors or Phosphodiesterase 4 inhibitor (Crisaborole); b) or that topical treatments were otherwise not recommended. Group 2- Dupilumab-Inadequate Responder: Documented history of an IR to dupilumab: a) either following at least 16 weeks of treatment according to the Investigator's judgement; b) or intolerant to dupilumab owing to adverse events. Exclusion Criteria: Other than AtD, the presence of a significant skin morbidity that will influence the Investigator's ability to assess the severity of the disease (e.g. psoriasis, confirmed or suspected cutaneous T-cell lymphoma, autoimmune bullous disease, fixed drug reaction and Stevens Johnson Syndrome). Participants with any uncontrolled medical conditions, other than AtD, that in the opinion of the investigator puts the participant at unacceptable risk or will likely interfere with study assessments or data integrity. Other medical conditions should be stable at the time of screening and be expected to remain stable for the duration of the study. Treatment with biologic agents (investigational and marketed monoclonal antibodies) within 12 weeks or 5 pharmacokinetic half-lives (whichever is longer) prior dosing on Day 1. Treatment with Janus Activated Kinase inhibitors (e.g. baricitinib, upadacitinib) within 4 weeks or 5 half-lives (whichever is longer) prior to dosing on Day 1. Mycophenolate mofetil, azathioprine, methotrexate, or calcineurin inhibitors within 4 weeks of Screening.

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: Group 1: Biologic Naïve participants receiving GSK1070806<br> | Drug: GSK1070806<br>* GSK1070806 will be administered<br>|
| Placebo Comparator: Group 1: Biologic Naïve participants receiving Placebo<br> | Drug: Placebo<br>* Placebo will be administered<br>|
| Experimental: Group 2: Dupilumab inadequate responders receiving GSK1070806<br> | Drug: GSK1070806<br>* GSK1070806 will be administered<br>|
| Placebo Comparator: Group 2: Dupilumab inadequate responders receiving Placebo<br> | Drug: Placebo<br>* Placebo will be administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from Baseline in Eczema Area and Severity Index (EASI) at Week 12 in Group 1 | EASI is an investigator-assessed measure that is used to assess the extent (area) and severity of AtD. The range of the scale is 0-72, with a higher score indicating greater severity. | Baseline and at Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in EASI at Week 12 in Group 1 | EASI is an investigator-assessed measure that is used to assess the extent (area) and severity of AtD. The range of the scale is 0-72, with a higher score indicating greater severity. | Baseline and at Week 12 | 
| Percentage of participants achieving >=50/75/90 percent reduction in EASI from Baseline at Week 12 in Group 1 |  | Baseline to Week 12 | 
| Investigator Global Assessment (IGA) Score of 0 or 1 at Week 12 in Group 1 | IGA for AtD is a measure of overall disease severity at the time of assessment. It is measured on a 5 point scale where, 0=Clear; 1= Almost clear; 2=Mild disease; 3=Moderate disease; 4=Severe disease. | At Week 12 | 
| Percent Change from Baseline in EASI at Week 12 in Group 2 | EASI is an investigator-assessed measure that is used to assess the extent (area) and severity of AtD. The range of the scale is 0-72, with a higher score indicating greater severity. | Baseline and at Week 12 | 
| Number of Participants with Serious Adverse Events (SAEs) and Adverse Events (AEs) - Groups 1 and 2 |  | Up to Week 24 | 
| Number of Participants with Clinically Significant findings in Vital signs, 12-lead Electrocardiogram (ECG) and Laboratory Parameters- Groups 1 and 2 |  | Up to Week 24 | 
| Number of Participants With Positive Anti-drug Antibodies (ADA)- Groups 1 and 2 |  | Up to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eczema activity severity index, GSK1070806