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A Dose-Finding Study of GSK2894512 Cream in Subjects With Atopic Dermatitis (AD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02564055
Recruitment Status : Completed
First Posted : September 30, 2015
Results First Posted : November 20, 2017
Last Update Posted : November 20, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This study will evaluate the efficacy and safety of two concentrations (0.5 percent [%] and 1%) and two application frequencies (once a day and twice a day) of GSK2894512 cream for the topical treatment in adolescent and adult subjects with atopic dermatitis. Results from this study will be considered when selecting the most appropriate concentration of GSK2894512 cream and application frequency in future clinical studies. This is a multicenter (United States, Canada, and Japan), randomized, double-blind (sponsor-unblind), vehicle-controlled, 6-arm, parallel-group, dose-finding study in adolescent and adult subjects with atopic dermatitis. Two concentrations of GSK2894512 cream (0.5% and 1%) and a vehicle control cream will be equally randomized and evaluated following application to all atopic dermatitis lesions (except on the scalp) once daily (evening) or twice daily (morning and evening) for 12 weeks. This study will consist of 3 periods: up to 4 weeks screening, 12 weeks double-blind treatment, and 4 weeks post-treatment follow-up. The total duration of subject participation will be approximately 16 to 20 weeks. Approximately 270 adolescent and adult males and females subjects with atopic dermatitis will be screened in order to have at least 228 randomized subjects (38 subjects for each of the 6 treatment groups) and approximately 204 evaluable subjects overall. Approximately 30 subjects will be randomized in Japan to achieve at least 24 evaluable Japanese subjects.

Condition or disease Intervention/treatment Phase
Dermatitis, Atopic Drug: GSK2894512 1% Cream Drug: GSK2894512 0.5% Cream Drug: Vehicle cream Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 247 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Study 203121: A Randomized, Blinded, Vehicle-Controlled, Dose-Finding Study of GSK2894512 Cream for the Treatment of Atopic Dermatitis
Study Start Date : December 1, 2015
Actual Primary Completion Date : January 1, 2017
Actual Study Completion Date : January 12, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema

Arm Intervention/treatment
Experimental: GSK2894512 1% cream twice daily
Subjects will apply a thin layer of GSK2894512 1% (10 milligram per gram [mg/g]) topical cream twice daily (morning and evening) for 12 weeks, to all atopic dermatitis lesions (except on the scalp).
Drug: GSK2894512 1% Cream
1.0% (10 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically

Experimental: GSK2894512 1% cream once daily
Subjects will apply a thin layer of GSK2894512 1% (10 mg/g) topical cream once daily (evening) for 12 weeks, to all atopic dermatitis lesions (except on the scalp).
Drug: GSK2894512 1% Cream
1.0% (10 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically

Experimental: GSK2894512 0.5% cream twice daily
Subjects will apply a thin layer of GSK2894512 0.5% (5 mg/g) topical cream twice daily (morning and evening) for 12 weeks, to all atopic dermatitis lesions (except on the scalp).
Drug: GSK2894512 0.5% Cream
0.5% (5 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically

Experimental: GSK2894512 0.5% cream once daily
Subjects will apply a thin layer of GSK2894512 0.5% (5 mg/g) topical cream once daily (evening) for 12 weeks, to all atopic dermatitis lesions (except on the scalp).
Drug: GSK2894512 0.5% Cream
0.5% (5 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically

Placebo Comparator: Vehicle cream twice daily
Subjects will apply a thin layer of vehicle topical cream twice daily (morning and evening) for 12 weeks, to all atopic dermatitis lesions (except on the scalp).
Drug: Vehicle cream
White to off-white vehicle cream base to be applied topically

Placebo Comparator: Vehicle cream once daily
Subjects will apply a thin layer of vehicle topical cream once daily (evening) for 12 weeks, to all atopic dermatitis lesions (except on the scalp).
Drug: Vehicle cream
White to off-white vehicle cream base to be applied topically




Primary Outcome Measures :
  1. Percentage of Participants Who Have an Investigator Global Assessment (IGA) Score of Clear or Almost Clear (0 or 1) at Week 12 and a Minimum 2 Grade Improvement in IGA Score From Baseline to Week 12 for Intent to Treat (ITT) Population [ Time Frame: Baseline and up to Week 12 ]
    The IGA is a clinical tool for assessing the current state/severity of a participant's AD. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines. The percentage of participants who have an IGA score of clear or almost clear at Week 12 and a minimum 2 grade improvement from Baseline to Week 12 in IGA score was presented. . The analysis was performed on ITT Population which comprised of all randomized participants.


Secondary Outcome Measures :
  1. Mean Change From Baseline in Weekly Average of Daily Itch/Pruritus (Numeric Rating Scale [NRS]) Score [ Time Frame: Baseline and up to Week 12 ]
    NRS is a 11-point tool ranging from 0 (absent) to 10 (worst imaginable) to assess the severity of 11 disease-related signs and symptoms including itching, discoloration, bleeding, oozing, cracking, scaling, flaking, dry/rough, painful, burning, and stinging. Participants were asked to complete the self-administered sign and symptom severity diary containing NRS using a recall period of the past 24 hours. Question 1 of the diary was used to assess itch. Mean change from Baseline to Week 12 in weekly average of daily itch/pruritus based on the NRS was presented using mean and standard deviation (SD). Baseline was defined as the latest assessment prior to first dose and Change from Baseline was defined as post-dose weekly average value minus Baseline value.

  2. Mean Percent Change From Baseline in Weekly Average of Daily Itch/Pruritus NRS Score [ Time Frame: Baseline and up to Week 12 ]
    NRS is a 11-point tool ranging from 0 (absent) to 10 (worst imaginable) to assess the severity of 11 disease-related signs and symptoms including itching, discoloration, bleeding, oozing, cracking, scaling, flaking, dry/rough, painful, burning, and stinging. Participants were asked to complete the self-administered sign and symptom severity diary containing NRS using a recall period of the past 24 hours. Question 1 of the diary was used to assess itch. Mean percent change in weekly average of daily itch/pruritus based on the NRS was presented using mean and SD from Baseline to Week 12. Baseline was defined as the latest assessment prior to first dose and Change from Baseline was defined as post-dose weekly average value minus Baseline value.

  3. Percentage of Participants Who Achieve a Minimum 3- Point Improvement in Itch/Pruritus (NRS) From Baseline to Each Study Visit [ Time Frame: Week 1, 2, 4, 8, 12, 14, 16, early withdrawal (EW) (up to Week 16) ]
    NRS is a 11-point tool ranging from 0 (absent) to 10 (worst imaginable) to assess the severity of 11 disease-related signs and symptoms including itching, discoloration, bleeding, oozing, cracking, scaling, flaking, dry/rough, painful, burning, and stinging. Participants were asked to complete the self-administered sign and symptom severity diary containing NRS using a recall period of the past 24 hours. Question 1 of the diary was used to assess itch. Percentage of participants who achieved a minimum 3-point improvement in itch/pruritus (NRS) from Baseline to each study visit were measured. Baseline was defined as the latest assessment prior to first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

  4. Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score [ Time Frame: Week 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    The EASI scoring system is a standard clinical tool for assessing the severity of AD that takes into account the overall severity of erythema, infiltration/papulation, excoriation, and lichenification, as well as the extent of BSA affected with AD. These 4 clinical signs were graded on a 4-point scale (0 [absent] to 3 [severe]) for each of the 4 specified body regions (head and neck, upper extremities, lower extremities, and trunk). Body area involvement ranged from 0 (0%) to 6 (90-100%). Total EASI score was calculated as a sum of scores of all 4 specified body region. Range for EASI total score is 0 (absent) to 72 (severe). Baseline was defined as the latest assessment prior to first dose and change from Baseline was defined as post dose visit value minus Baseline value. Mean change from Baseline was presented in the form of mean and SD. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  5. Mean Percent Change From Baseline in EASI Score [ Time Frame: Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    The EASI scoring system is a standard clinical tool for assessing the severity of AD that takes into account the overall severity of erythema, infiltration/papulation, excoriation, and lichenification, as well as the extent of BSA affected with AD. These 4 clinical signs were graded on a 4-point scale (0 [absent] to 3 [severe]) for each of the 4 specified body regions (head and neck, upper extremities, lower extremities, and trunk). Body area involvement ranged from 0 (0%) to 6 (90-100%). Total EASI score was calculated as a sum of scores of all 4 specified body region. Range for EASI total score is 0 (absent) to 72 (severe). Baseline was defined as the latest assessment prior to first dose and change from Baseline was defined as post dose visit value minus Baseline value. Mean percent change from Baseline was presented in the form of mean and SD. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  6. Percentage of Participants With a Minimum 2-grade Improvement in IGA Score From Baseline to Each Visit [ Time Frame: Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    The IGA is a clinical tool for assessing the current state/severity of a participant's AD. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines. IGA is made without reference to previous scores. The percentage of participants with a minimum 2-grade improvement in IGA score from Baseline at Week 1, Week 2, Week 4, Week 8, Week 12, Week 14 (follow up 1), Week 16 (follow up 2) and early withdrawal (EW) visit was presented in the form of mean and SD. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  7. Percentage of Participants With an IGA Score of 0 or 1 at Each Visit [ Time Frame: Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    The IGA is a clinical tool for assessing the current state/severity of a participant's AD. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines. IGA is made without reference to previous scores. The percentage of participants with an IGA score of 0 or 1 at Week 1, Week 2, Week 4, Week 8, Week 12, Week 14 (follow up 1), Week 16 (follow up 2) and EW visit was presented in the form of mean and SD. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  8. Percentage of Participants With >=50 Percent Improvement From Baseline in EASI [ Time Frame: Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    The EASI scoring system is a standard clinical tool for assessing the severity of AD that takes into account the overall severity of erythema, infiltration/papulation, excoriation, and lichenification, as well as the extent of BSA affected with AD. These 4 clinical signs were graded on a 4-point scale for each of the 4 specified body regions (head and neck, upper extremities, lower extremities, and trunk). Percentage of participants with >=50 percent improvement in EASI score from Baseline to Week 1, Week 2, Week 4, Week 8, Week 12, Week 14 (follow up 1), Week 16 (follow up 2) and EW were presented and statistical analysis was performed using a repeated measures factorial logistic regression model. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  9. Percentage of Participants With >=75 Percent Improvement From Baseline in EASI [ Time Frame: Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    The EASI scoring system is a standard clinical tool for assessing the severity of AD that takes into account the overall severity of erythema, infiltration/papulation, excoriation, and lichenification, as well as the extent of BSA affected with AD. These 4 clinical signs were graded on a 4-point scale for each of the 4 specified body regions (head and neck, upper extremities, lower extremities, and trunk). Percentage of participants with >=75 percent improvement in EASI score from Baseline to Week 1, Week 2, Week 4, Week 8, Week 12, Week 14 (follow up 1), Week 16 (follow up 2) and EW were presented and statistical analysis was performed using a repeated measures factorial logistic regression model. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  10. Mean Change From Baseline in Total Severity Score (TSS) [ Time Frame: Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    A target lesion of at least 3 centimeter square (cm^2) was selected at Baseline. The severity of the following signs: erythema, induration/papulation, lichenification, oozing/crusting, and scaling was assessed on a 4-point scale ranging from 0 (absent) to 3 (severe), with higher values indicating greater severity of symptoms. TSS (maximum score 15) was calculated based on these signs. Mean change from Baseline in TSS at Week 1, Week 2, Week 4, Week 8, Week 12, Week 14 (follow up 1), Week 16 (follow up 2) and EW visit was presented using mean and SD. Baseline value was defined as the latest assessment prior to first dose and change from Baseline was defined as post dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  11. Mean Percent Change From Baseline in TSS [ Time Frame: Week 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    A target lesion of at least 3 cm^2 was selected at Baseline. The severity of the following signs: erythema, induration/papulation, lichenification, oozing/crusting, and scaling was assessed on a 4-point scale ranging from 0 (absent) to 3 (severe) , with higher values indicating greater severity of symptoms. TSS (maximum score 15) was calculated based on these signs. Mean percent change from Baseline in TSS at Week 1, Week 2, Week 4, Week 8, Week 12, Week 14 (follow up 1), Week 16 (follow up 2) and EW visit was presented using mean and SD. Baseline value was defined as the latest assessment prior to first dose and change from Baseline was defined as post dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  12. Mean Change From Baseline in Individual Signs of TSS [ Time Frame: Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    The severity of the following signs: erythema, induration/papulation, lichenification, oozing/crusting, and scaling was assessed on a 4-point scale ranging from 0 (absent) to 3 (severe) and TSS (maximum score 15) was calculated based on these signs. Mean change from Baseline in individual signs of TSS was presented using mean and SD. Baseline value was defined as the latest assessment prior to first dose and change from Baseline was defined as post dose visit value minus Baseline value. If the participant had more than 3 missing days during the week, then the weekly average was not calculated and treated as missing data and excluded from the analysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  13. Mean Percent Change From Baseline in Individual Signs of TSS [ Time Frame: Week 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    The severity of the following signs: erythema, induration/papulation, lichenification, oozing/crusting, and scaling was assessed on a 4-point scale ranging from 0 (absent) to 3 (severe) and TSS (maximum score 15) was calculated based on these signs. Mean percent change from Baseline in individual signs of TSS was presented using mean and SD. Baseline value was defined as the latest assessment prior to first dose and change from Baseline was defined as post dose visit value minus Baseline value. NA indicates that data were not available. If the participant had more than 3 missing days during the week, then the weekly average was not calculated and treated as missing data and excluded from the analysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  14. Mean Change From Baseline in Body Surface Area (Percent BSA) [ Time Frame: Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    The extent of BSA affected by AD is a general indicator of disease severity and the assessment of BSA with AD was performed separately for four body surface regions: the head (h), the upper extremities (u), the trunk (t) and the lower extremities (l), corresponding to 10, 20, 30, and 40 percent of the total body area, respectively. Mean change from Baseline in percent BSA was presented using mean and SD at Week 1, Week 2, Week 4, Week 8, Week 12, Week 14 (follow up 1), Week 16 (follow up 2) and EW visit. Baseline was defined as the latest assessment prior to first dose and change from Baseline was defined as post dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  15. Mean Change From Baseline in IGA Score [ Time Frame: Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16) ]
    The IGA is a clinical tool for assessing the current state/severity of a participant's AD. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines. IGA is made without reference to previous scores. Score ranges from 0 (clear) to 4 (severe). Higher values represent a severe disease. Mean change from Baseline in IGA score was presented using mean and SD at Week 1, Week 2, Week 4, Week 8, Week 12, Week 14 (follow up 1), Week 16 (follow up 2) and EW visit. Baseline was defined as the latest assessment prior to first dose and change from Baseline was defined as post dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  16. Percentage of Participants Who Have an IGA Score of Clear or Almost Clear (0 or 1) and a Minimum 2 Grade Improvement in IGA Score From Baseline to Each Study Visit [ Time Frame: Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to week 16) ]
    The IGA is a clinical tool for assessing the current state/severity of a participant's AD. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines. IGA is made without reference to previous scores. The percentage of participants who have an IGA score of clear or almost clear and a minimum 2 grade improvement from Baseline to each study visit in IGA score was presented. The statistical analysis was performed using a repeated measures factorial logistic regression model with covariates for dose, frequency of administration, and study day as well as a dose by frequency interaction term. The analysis was performed on ITT Population which comprised of all randomized participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category title).

  17. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: Weeks 1, 2, 4, 8, 12, 14, EW (up to week 14) ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function. Treatment emergent AEs (TEAE) is defined as AE occurred on or after study treatment start date and on or before last visit. Number of participants with AEs and serious TEAEs were presented. The analysis was performed on Safety population which comprised of all participants who receive at least one dose of study treatment.

  18. Number of Participants With Reported Tolerability Score of 0 to 4 Over Time [ Time Frame: Week 1, 2, 4, 8, 12, 14, EW (up to Week 14) ]
    Participants were asked to use a 5-point tolerability scale from 0 (none) to 4 (severe) to assess the presence and degree of burning/stinging and itching at the application sites that has generally been experienced following application of the study treatment. The score represented an 'average' across all application sites. A score of 3 or 4 was reported as an AE. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

  19. Change From Baseline in Albumin and Total Protein [ Time Frame: Week 1, 2, 4, 8, 12, 14, EW (up to week 14) ]
    Blood samples were collected to evaluate change from Baseline in albumin and total protein values at Baseline throughout the 12 weeks of study treatment and follow up visit 1 at Week 14. Baseline values were taken at Day 1 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  20. Change From Baseline in Alkaline Phosphatase (Alk.Phosph.), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) [ Time Frame: Week 2, 4, 8, 12, 14, EW (up to week 14) ]
    Blood samples were collected to evaluate change from Baseline in Alk.phosph., ALT, AST and GGT values at Baseline throughout the 12 weeks of study treatment and follow up visit 1 at Week 14. Baseline values were taken at Day 1 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  21. Change From Baseline in Direct and Total Bilirubin, Creatinine and Urate [ Time Frame: Week 2, 4, 8, 12, 14, EW (up to week 14) ]
    Blood samples were collected to evaluate change from Baseline in direct and total bilirubin, creatinine and urate values at Baseline throughout the 12 weeks of study treatment and follow up visit 1 at Week 14. Baseline values were taken at Day 1 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  22. Change From Baseline in Calcium, Chloride, Carbon Dioxide (CO2), Glucose, Potassium, Sodium, Blood Urea Nitrogen (BUN) [ Time Frame: Week 2, 4, 8, 12, 14, EW (up to week 14) ]
    Blood samples were collected to evaluate change from Baseline in calcium, chloride, CO2, glucose, potassium, sodium and BUN values at Baseline throughout the 12 weeks of study treatment and follow up visit 1 at Week 14. Baseline values were taken at Day 1 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  23. Number of Participants With Chemistry Data of Potential Clinical Importance [ Time Frame: Week 2, 4, 8, 12, 14, EW (up to week 14) ]
    Blood samples were collected from participants for evaluation of clinical chemistry parameters by Potential Clinical Importance Criteria from Baseline to Week 14, EW and any visit post-screen. The vital signs included alk.phosph., ALT, AST, bilirubin, calcium, CO2, creatinine, glucose and potassium. Baseline was defined as the latest assessment prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

  24. Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet, Leukocytes Count [ Time Frame: Week 2, 4, 8, 12, 14, EW (up to week 14) ]
    Blood samples were collected to evaluate change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet and leukocytes and values at Baseline throughout the 12 weeks of study treatment and follow up visit 1 at Week 14. Baseline values were taken at Day 1 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  25. Change From Baseline in Hematocrit Levels [ Time Frame: Week 2, 4, 8, 12, 14, EW (up to week 14) ]
    Blood samples were collected to evaluate change from Baseline in hematocrit and values at Baseline throughout the 12 weeks of study treatment and follow up visit 1 at Week 14. Baseline values were taken at Day 1 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  26. Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) [ Time Frame: Week 2, 4, 8, 12, 14, EW (up to week 14) ]
    Blood samples were collected to evaluate change from Baseline in hemoglobin and MCHC and values at Baseline throughout the 12 weeks of study treatment and follow up visit 1 at Week 14. Baseline values were taken at Day 1 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  27. Change From Baseline in Mean Corpuscle Hemoglobin (MCH) [ Time Frame: Week 2, 4, 8, 12, 14, EW (up to week 14) ]
    Blood samples were collected to evaluate change from Baseline in MCH and values at Baseline throughout the 12 weeks of study treatment and follow up visit 1 at Week 14. Baseline values were taken at Day 1 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  28. Change From Baseline in Mean Corpuscle Volume (MCV) [ Time Frame: Week 2, 4, 8, 12, 14, EW (up to week 14) ]
    Blood samples were collected to evaluate change from Baseline in MCV and values at Baseline throughout the 12 weeks of study treatment and follow up visit 1 at Week 14. Baseline values were taken at Day 1 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  29. Change From Baseline in Erythrocyte Count [ Time Frame: Weeks 2, 4, 8, 12, 14, EW (week up to 14) ]
    Blood samples were collected to evaluate change from Baseline in erythrocytes and values at Baseline throughout the 12 weeks of study treatment and follow up visit 1 at Week 14. Baseline values were taken at Day 1 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  30. Number of Participants With Hematology Data of Potential Clinical Importance [ Time Frame: Baseline, Week 2, 4, 8, 12, 14, early withdrawal, and post screen (up to Week 16) ]
    Blood samples were collected from participants for evaluation of hematology parameters by Potential Clinical Importance Criteria from Baseline to Week 14, EW and any visit post-screen. The vital signs included hematocrit, hemoglobin, lymphocytes, neutrophils, platelet and leukocytes. Baseline was defined as the latest assessment prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

  31. Change From Baseline in Total T Lymphocytes (Lympho), B Lympho, Natural Killer (NK) Lymphocytes and Treg (Foxp3) Levels [ Time Frame: Week, 4, 8 and 12 ]
    Blood samples were collected to evaluate change from Baseline in total T lympho, B lympho, T and B NK cells and (Foxp3) values at Baseline throughout the 12 weeks of study treatment. The immunophenotyping parameters included cluster of differentiation (CD)19, CD3, CD3+CD8+, CD3+CD4+, CD16+CD56+, CD3+CD4+CD25+CD127, CD3+CD4+foxP3+CD25+CD127 and T and NK lympho. CD3, CD3+CD8+ and CD3+CD4+ were also evaluated by using treg flow cytometry (cyto). Baseline was defined as the latest assessment prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  32. Number of Participants With Immunopheotyping Data Outside the Reference Range [ Time Frame: Baseline, Week, 4, 8, 12 and post-screen (up to Week 16) ]
    Blood samples were collected from participants for evaluation of immunophenotyping parameters by Potential Clinical Importance Criteria at Baseline, Week 4, Week 8, Week 12 nd any visit post-screen. The immunophenotyping parameters included CD 19, CD3, CD3+CD8+, CD3+CD4+, CD16+CD56+, CD3+CD4+CD25+CD127, CD3+CD4+foxP3+CD25+CD127 and T and NK lympho. CD3, CD3+CD8+ and CD3+CD4+ were also evaluated by using treg flow cyto. Baseline was defined as the latest assessment prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

  33. Change From Baseline in Immunoglobin (Ig) A, IgG and IgM Levels [ Time Frame: Week, 4, 8 and 12 ]
    Blood samples were collected to evaluate change from Baseline in IgA, IgG, IM values at Baseline throughout the 12 weeks of study treatment. Baseline values were taken at Day 1 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  34. Number of Participants With Immunoglobulin Data Outside the Reference Range [ Time Frame: Baseline, Week, 4, 8, 12, post-screen (up to Week 16) ]
    Blood samples were collected from participants for evaluation of immunoglobulin data outside the reference range at Baseline, Week 4, Week 8, Week 12 and any visit post-screen. The immunoglobulin parameters included IgA, IgG and Ig M. Baseline was defined as the latest assessment prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

  35. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: Week 1, 2, 4, 8, 12, 14, EW (up to week 14) ]
    SBP and DBP were measured from Baseline up to follow up Visit 1 at Week 14 in semi-supine position after at least 5 minutes of rest. The Baseline value was taken at Day 1 and change from Baseline was defined as post dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  36. Change From Baseline in Pulse Rate [ Time Frame: Week 1, 2, 4, 8, 12, 14, EW (up to week 14) ]
    Pulse rate were measured from Baseline up to follow up Visit 1 at Week 14 in semi-supine position after at least 5 minutes of rest. The Baseline value was taken at Day 1 and change from Baseline was defined as post dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  37. Change From Baseline in Temperature [ Time Frame: Week 1, 2, 4, 8, 12, 14, EW (up to week 14) ]
    Temperature were measured from Baseline up to follow up Visit 1 at Week 14 in semi-supine position after at least 5 minutes of rest. The Baseline value was taken at Day 1 and change from Baseline was defined as post dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and SD were measured.

  38. Number of Participants With Vital Signs of Potential Clinical Importance [ Time Frame: Baseline, Week 2, 4, 8, 12, 14, EW (up to week 14) ]
    Blood samples were collected from participants for evaluation of vital signs by Potential Clinical Importance Criteria from Baseline to Week 14, EW and any visit post-screen. The vital signs included SBP, DBP and pulse rate. Baseline was defined as the latest assessment prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

  39. Number of Participants With Abnormal Electrocardiogram (ECG) Findings [ Time Frame: Baseline, Week 1, 12, 14, EW ( up to Week 14), post-screen ]
    Single measurements of 12-lead ECGs were obtained at Baseline , Week 1, Week 12, Week 14 (follow up 1), EW and at any time post-screen using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc). Baseline was defined as the latest assessment prior to the first dose. For multiple ECGs at one visit, or "Any visit post-screen", a participant was categorized as "Abnormal" if >=1 assessment was abnormal. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female between 12 and 65 years of age inclusive, at the time of signing the informed consent
  • Diagnosis of atopic dermatitis according to Hanifin and Rajka criteria and having active inflammation.
  • Body surface area involvement >=5% and <=35%, excluding scalp, at Screening and Baseline.
  • An IGA of atopic dermatitis score of >=3 at Baseline.
  • At least one target lesion that measure at least 3 centimetre (cm) х 3 cm in size at Screening and Baseline and must be representative of the subject's disease state, but not located on the hands, feet, or genitalia.
  • A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: 1) Pre-menopausal females with one of the following procedures documented: tubal ligation; hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; bilateral oophorectomy. 2) Post-menopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone and estradiol levels consistent with menopause and falling into the central laboratory's postmenopausal reference range is confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt are required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment; Reproductive potential and agrees to follow one of the options listed in the modified list of highly effective methods for avoiding pregnancy in females of reproductive potential from 30 days prior to the first dose of study medication and until after the last dose of study medication and completion of the follow-up visit.

Exclusion Criteria:

  • Unstable course of atopic dermatitis (spontaneously improving or rapidly deteriorating) as determined by the investigator over the previous 4 weeks prior to Baseline.
  • Concurrent conditions and history of other diseases: 1) Immunocompromized (eg, lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich Syndrome) or have a history of malignant disease within 5 years before the baseline visit; 2) Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks before the baseline visit; 3) Active acute bacterial, fungal, or viral (eg, herpes simplex, herpes zoster, chicken pox) skin infection within 1 week before the baseline visit; 4) Any other concomitant skin disorder (eg, generalized erythroderma such as Netherton's Syndrome, or psoriasis); pigmentation, or extensive scarring that in the opinion of the investigator may interfere with the evaluation of AD lesions or compromise subject safety; 5) Presence of AD lesions only on the hands or feet without prior history of involvement of other classical areas of involvement such as the face or the folds; 6) Other types of eczema.
  • A history or ongoing serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, may interfere with the subject's completion of the study.
  • Known hypersensitivity to study treatment excipients.
  • Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result within 3 months of screening.
  • Liver function tests: alanine aminotransferase (ALT) >=2x upper limit of normal (ULN); alkaline phosphatase and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • QTc >=450 milliseconds (msec) or QTc >=480 msec for subjects with bundle branch block.

NOTES: The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), with machine over-read. The QTc should be based on a single ECG obtained over a brief recording period. If QTc is outside of the threshold value, triplicate ECGs may be performed with the QTc values averaged.

  • Ultraviolet (UV) light therapy or prolonged exposure to natural or artificial sources of UV radiation (eg, sunlight or tanning booth) within 4 weeks prior to the baseline visit and/or intention to have such exposure during the study, which is thought by the investigator to potentially impact the subject's atopic dermatitis.
  • Used any of the following treatments within the indicated washout period before the baseline visit: 12 weeks or 5 half-lives (whichever is longer) - biologic agents (eg, 18 weeks for omalizumab); 8 weeks - cyclosporin, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg, mycophenolate or tacrolimus); 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogs; 2 weeks - topical treatments: corticosteroids, calcineurin inhibitors, or coal tar (on the body); 2 weeks - immunizations; sedating antihistamines (non sedating antihistamines are permitted); 1 week - topical antibiotics, antibacterial cleansing body wash/soap or diluted sodium hypochlorite "bleach" baths.
  • Participated in a clinical study and received an investigational product within the following time period prior to the baseline visit: 4 weeks, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer).
  • History of alcohol or other substance abuse within the last 2 years.
  • Participated in a previous study using GSK2894512 (or WBI-1001).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02564055


Locations
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Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02564055    
Other Study ID Numbers: 203121
First Posted: September 30, 2015    Key Record Dates
Results First Posted: November 20, 2017
Last Update Posted: November 20, 2017
Last Verified: August 2017
Keywords provided by GlaxoSmithKline:
Vehicle-Controlled
GSK2894512
Double blind
Dose-finding
Atopic Dermatitis
Additional relevant MeSH terms:
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Dermatitis, Atopic
Dermatitis
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases