Clinical Effect, Safety and Tolerability of GSK1070806 in Atopic Dermatitis

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

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

Study Overview

• Status: Completed
• Conditions: Dermatitis, Atopic
• Intervention / Treatment: Drug: Placebo; Drug: GSK1070806

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1C3
      • GSK Investigational Site
  • Ontario
    • London, Ontario, Canada, N6A 5R9
      • GSK Investigational Site
    • London, Ontario, Canada, N6H 5L5
      • GSK Investigational Site
• United States
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
      • GSK Investigational Site
  • Florida
    • Miami, Florida, United States, 33155
      • GSK Investigational Site
    • Tampa, Florida, United States, 33613
      • GSK Investigational Site
  • Michigan
    • Troy, Michigan, United States, 48084
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73118
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • GSK Investigational Site
  • Texas
    • San Antonio, Texas, United States, 78218
      • GSK Investigational Site
    • Sugar Land, Texas, United States, 77479
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: GSK1070806; Participants received a single dose of 2 mg/kg GSK1070806 as intravenous infusion on Day 1.	Drug: GSK1070806; GSK1070806 will be administered
Placebo Comparator: Group 1: Placebo; Participants received Placebo as intravenous infusion on Day 1.	Drug: Placebo; Placebo will be administered
Experimental: Group 2: Dupilumab-IR with GSK1070806; Participants received a single dose of 2 mg/kg GSK1070806 as intravenous infusion on Day 1.	Drug: GSK1070806; GSK1070806 will be administered
Placebo Comparator: Group 2: Dupilumab IR with Placebo; Participants received Placebo as intravenous infusion on Day 1.	Drug: Placebo; Placebo will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline (PCFB) in Eczema Area and Severity Index (EASI) Score at Week 12 in Group 1	EASI scoring system is standardized clinical tool for assessment of extent (area) and severity of atopic dermatitis (AD). Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk and lower limbs on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % body surface area with AD in body region: 0 (0%), 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100% The final EASI score was obtained by weight-averaging these 4 scores and scores ranged from 0 to 72, with higher scores= more severe or extensive condition. Posterior Median presented from Bayesian analysis under the hypothetical strategy. The percent change from baseline in the EASI score at week 12 in group 1 is reported here. Data reported as 'Median' refers to 'Posterior Median' and '95% Confidence Interval' refers to '95% Credible Interval'.	Baseline (Day 1) and at Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in EASI Score at Week 12 in Group 1	EASI scoring system is standardized clinical tool for assessment of extent (area) and severity of atopic dermatitis (AD). Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk and lower limbs on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % body surface area with AD in body region: 0 (0%), 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100% The final EASI score was obtained by weight-averaging these 4 scores and scores ranged from 0 to 72, with higher scores= more severe or extensive condition. Posterior Median presented from Bayesian analysis under the hypothetical strategy. The change from baseline in the EASI score at week 12 in group 1 is reported here. Data reported as 'Median' refers to 'Posterior Median' and '95% Confidence Interval' refers to '95% Credible Interval'.	Baseline (Day 1) and at Week 12
Number of Participants Achieving EASI-50, ≥ 50% Reduction in EASI Score at Week 12 in Group 1	EASI scoring system is standardized clinical tool for assessment of extent (area) and severity of atopic dermatitis (AD). Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk and lower limbs on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % body surface area with AD in body region: 0 (0%), 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100% The final EASI score was obtained by weight-averaging these 4 scores and scores ranged from 0 to 72, with higher scores= more severe or extensive condition. The EASI-50 responder is defined as a participant who achieves a ≥ 50% improvement from baseline in the EASI score.	At Week 12
Number of Participants Achieving EASI-75, ≥ 75% Reduction in EASI Score at Week 12 in Group 1	EASI scoring system is standardized clinical tool for assessment of extent (area) and severity of atopic dermatitis (AD). Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk and lower limbs on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % body surface area with AD in body region: 0 (0%), 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100% The final EASI score was obtained by weight-averaging these 4 scores and scores ranged from 0 to 72, with higher scores= more severe or extensive condition. The EASI-75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score.	At Week 12
Number of Participants Achieving EASI-90, ≥ 90% Reduction in EASI Score at Week 12 in Group 1	EASI scoring system is standardized clinical tool for assessment of extent (area) and severity of atopic dermatitis (AD). Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk and lower limbs on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % body surface area with AD in body region: 0 (0%), 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100% The final EASI score was obtained by weight-averaging these 4 scores and scores ranged from 0 to 72, with higher scores= more severe or extensive condition. The EASI-90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the EASI score.	At Week 12
Number of Participants With Investigator Global Assessment (IGA) Score of 0 or 1 at Week 12 in Group 1	The Investigator Global Assessment (IGA) is a clinical tool for assessing the current state/severity of a participant's atopic dermatitis. It is a static 5-point morphological assessment of overall disease severity determined by the investigator, sub-investigator, or trained healthcare professional with required qualifications on a scale of 0 to 4 where, 0-clear, 1-almost clear, 2-mild, 3-moderate, and 4- severe. Higher score indicates severity of disease. A Responder is defined as a participant who had an IGA score of 0 or 1 at each visit.	At Week 12
Percent Change From Baseline in EASI Score at Week 12 in Group 2	EASI scoring system is standardized clinical tool for assessment of extent (area) and severity of atopic dermatitis (AD). Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk and lower limbs on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % body surface area with AD in body region: 0 (0%), 1=1-9%; 2=10-29%; 3=30-49%; 4=50-69%; 5=70-89%; 6=90-100% The final EASI score was obtained by weight-averaging these 4 scores and scores ranged from 0 to 72, with higher scores= more severe or extensive condition. NA indicate that data is not available since only one participant was analyzed, therefore Standard Deviation (SD) was not derived.	Baseline (Day 1) and at Week 12
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) - Groups 1 and 2	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and other situations as per investigator's medical or scientific judgment.	Up to Week 24
Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline - Groups 1 and 2	Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate (PR) and body temperature were measured after resting for at least 5 minutes in semi-supine position. PCI ranges- SBP (millimeters of mercury[mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), PR (beats per minute): <40 (low) or >110 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants with worst case results relative to PCI criteria and who had values "to high" are reported here. Participants with a missing baseline value are assumed to have a within range value.	Up to Week 24
Number of Participants With Worst Case 12-lead Electrocardiogram (ECG) Post-Baseline Relative to Baseline - Groups 1 and 2	Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Participants with clinically significant changes relative to baseline are reported here. Clinically significant findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.	Up to Week 24
Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline - Groups 1 and 2	Urine samples were collected to assess urine glucose, bilirubin, protein, occult blood, Leukocyte Esterase and ketones using dipstick method. Participants with clinically significant changes relative to baseline are reported here. Clinically significant findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline was defined as the latest pre-dose assessment.	Up to Week 24
Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline - Groups 1 and 2	Blood samples were collected for analysis of chemistry parameters. PCI ranges were >3*Upper limit of normal (ULN) units per liter (U/L)(Alanine Aminotransferase [ALT]), >3*ULN (U/L) (Aspartate Aminotransferase ([AST]), >2*ULN (Alkaline Phosphatase [ALP]) (U/L), >2*ULN (micromoles per liter) (bilirubin), <3 or >6.5 mmol/L (potassium), <130 or >160 mmol/L (sodium), <1.5 or >3.25 mmol/L (Corrected Calcium) and >40 mmol/L (Urea). Participants with worst case results relative to PCI criteria and who had values "to high" are reported here. Participants with a missing baseline value are assumed to have a within range value.	Up to Week 24
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline - Groups 1 and 2	Blood samples were collected for analysis of hematology parameters. The ranges for the hematology parameters are as follows: Hematocrit [High >0.54 Proportion of red blood cells in blood, Low <0.1 Proportion of red blood cells in blood], Haemoglobin [Higher: > 185 grams/Litre (g/L) Low: less than (<) 100 g/L ], Lymphocytes [<0.8 10^9/L], Neutrophils [<1.5 10^9/L], Platelets [High: > 999 10^9/ L and Low: < 100 10^9/ L] and White blood cells [Low:<2 10^9/L]. Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' & 'To High', so the percentages may not add to 100%.	Up to Week 25
Number of Participants With Anti-drug Antibodies (ADA)- Groups 1 and 2	Serum samples were analyzed for the presence of antibodies using a validated assay method. The treatment emergent ADA assay results up to week 24 are reported.	Up to Week 24

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2021
• Primary Completion (Actual): December 19, 2022
• Study Completion (Actual): March 13, 2023

Study Registration Dates

• First Submitted: July 14, 2021
• First Submitted That Met QC Criteria: July 14, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Estimated): August 28, 2025
• Last Update Submitted That Met QC Criteria: August 6, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Eczema activity severity index; GSK1070806
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Dermatitis, Atopic; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs; GSK1070806
• Other Study ID Numbers: 215253

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No