Clinical Effect, Safety and Tolerability of GSK1070806 in Atopic Dermatitis

Phase 1

Completed

Conditions: Dermatitis, Atopic

Interventions: Drug: GSK1070806
Drug: Placebo

Registration Number: NCT04975438

Lead Sponsor: GlaxoSmithKline

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34

Inclusion Criteria

Not provided

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: GSK1070806	GSK1070806	Participants received a single dose of 2 mg/kg GSK1070806 as intravenous infusion on Day 1.
Group 1: Placebo	Placebo	Participants received Placebo as intravenous infusion on Day 1.
Group 2: Dupilumab-IR with GSK1070806	GSK1070806	Participants received a single dose of 2 mg/kg GSK1070806 as intravenous infusion on Day 1.
Group 2: Dupilumab IR with Placebo	Placebo	Participants received Placebo as intravenous infusion on Day 1.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline (PCFB) in Eczema Area and Severity Index (EASI) Score at Week 12 in Group 1	Baseline (Day 1) and at Week 12	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'.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Achieving EASI-90, ≥ 90% Reduction in EASI Score at Week 12 in Group 1	At Week 12	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.
Percent Change From Baseline in EASI Score at Week 12 in Group 2	Baseline (Day 1) and at Week 12	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.
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline - Groups 1 and 2	Up to Week 25	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%.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) - Groups 1 and 2	Up to Week 24	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.
Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline - Groups 1 and 2	Up to Week 24	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.
Number of Participants With Worst Case 12-lead Electrocardiogram (ECG) Post-Baseline Relative to Baseline - Groups 1 and 2	Up to Week 24	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.
Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline - Groups 1 and 2	Up to Week 24	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.
Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline - Groups 1 and 2	Up to Week 24	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.
Number of Participants With Anti-drug Antibodies (ADA)- Groups 1 and 2	Up to Week 24	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.
Number of Participants With Investigator Global Assessment (IGA) Score of 0 or 1 at Week 12 in Group 1	At Week 12	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.
Change From Baseline in EASI Score at Week 12 in Group 1	Baseline (Day 1) and at Week 12	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'.
Number of Participants Achieving EASI-75, ≥ 75% Reduction in EASI Score at Week 12 in Group 1	At Week 12	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.
Number of Participants Achieving EASI-50, ≥ 50% Reduction in EASI Score at Week 12 in Group 1	At Week 12	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.