Clinical Effect, Safety and Tolerability of GSK1070806 in Atopic Dermatitis

Phase 1CompletedNCT04975438

GlaxoSmithKline34 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Dermatitis, Atopic

Interventions

GSK1070806DRUG

GSK1070806 will be administered

PlaceboDRUG

Placebo will be administered

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (11)

GSK Investigational Site

North Little Rock, Arkansas, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

Outcomes

Primary Outcomes

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'.

Time frame: Baseline (Day 1) and at Week 12

Secondary Outcomes

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'.

Time frame: Baseline (Day 1) and at Week 12

Number of Participants Achieving EASI-50, ≥ 50% Reduction in EASI Score at Week 12 in Group 1

Data from ClinicalTrials.gov

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GSK Investigational Site

Troy, Michigan, United States

GSK Investigational Site

Oklahoma City, Oklahoma, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Sugar Land, Texas, United States

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

London, Ontario, Canada

...and 1 more locations

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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%.

Time frame: 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.

Time frame: Up to Week 24