Study 203121: A Randomized, Blinded, Vehicle-Controlled, Dose-Finding Study of GSK2894512 Cream for the Treatment of Atopic Dermatitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 247
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
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).
干预措施: GSK2894512 1% Cream (Drug)
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).
干预措施: GSK2894512 1% Cream (Drug)
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).
干预措施: GSK2894512 0.5% Cream (Drug)
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).
干预措施: GSK2894512 0.5% Cream (Drug)
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).
干预措施: Vehicle cream (Drug)
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).
干预措施: Vehicle cream (Drug)
结局指标
主要结局
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
时间窗: 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.
次要结局
- Mean Percent Change From Baseline in Weekly Average of Daily Itch/Pruritus NRS Score(Baseline and up to Week 12)
- Mean Change From Baseline in Weekly Average of Daily Itch/Pruritus (Numeric Rating Scale [NRS]) Score(Baseline and up to Week 12)
- Percentage of Participants Who Achieve a Minimum 3- Point Improvement in Itch/Pruritus (NRS) From Baseline to Each Study Visit(Week 1, 2, 4, 8, 12, 14, 16, early withdrawal (EW) (up to Week 16))
- Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score(Week 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16))
- Mean Percent Change From Baseline in EASI Score(Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16))
- Percentage of Participants With a Minimum 2-grade Improvement in IGA Score From Baseline to Each Visit(Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16))
- Percentage of Participants With an IGA Score of 0 or 1 at Each Visit(Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16))
- Percentage of Participants With >=50 Percent Improvement From Baseline in EASI(Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16))
- Percentage of Participants With >=75 Percent Improvement From Baseline in EASI(Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16))
- Mean Change From Baseline in Total Severity Score (TSS)(Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16))
- Mean Percent Change From Baseline in TSS(Week 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16))
- Mean Change From Baseline in Individual Signs of TSS(Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16))
- Mean Change From Baseline in Body Surface Area (Percent BSA)(Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16))
- Mean Change From Baseline in IGA Score(Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16))
- Mean Percent Change From Baseline in Individual Signs of TSS(Week 1, 2, 4, 8, 12, 14, 16, EW (up to Week 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(Weeks 1, 2, 4, 8, 12, 14, 16, EW (up to week 16))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs(Weeks 1, 2, 4, 8, 12, 14, EW (up to week 14))
- Number of Participants With Reported Tolerability Score of 0 to 4 Over Time(Week 1, 2, 4, 8, 12, 14, EW (up to Week 14))
- Change From Baseline in Total T Lymphocytes (Lympho), B Lympho, Natural Killer (NK) Lymphocytes and Treg (Foxp3) Levels(Week, 4, 8 and 12)
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Week 1, 2, 4, 8, 12, 14, EW (up to week 14))
- Change From Baseline in Albumin and Total Protein(Week 1, 2, 4, 8, 12, 14, EW (up to week 14))
- Number of Participants With Chemistry Data of Potential Clinical Importance(Week 2, 4, 8, 12, 14, EW (up to week 14))
- Change From Baseline in Alkaline Phosphatase (Alk.Phosph.), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT)(Week 2, 4, 8, 12, 14, EW (up to week 14))
- Change From Baseline in Pulse Rate(Week 1, 2, 4, 8, 12, 14, EW (up to week 14))
- Change From Baseline in Temperature(Week 1, 2, 4, 8, 12, 14, EW (up to week 14))
- Number of Participants With Vital Signs of Potential Clinical Importance(Baseline, Week 2, 4, 8, 12, 14, EW (up to week 14))
- Change From Baseline in Direct and Total Bilirubin, Creatinine and Urate(Week 2, 4, 8, 12, 14, EW (up to week 14))
- Change From Baseline in Calcium, Chloride, Carbon Dioxide (CO2), Glucose, Potassium, Sodium, Blood Urea Nitrogen (BUN)(Week 2, 4, 8, 12, 14, EW (up to week 14))
- Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet, Leukocytes Count(Week 2, 4, 8, 12, 14, EW (up to week 14))
- Change From Baseline in Hematocrit Levels(Week 2, 4, 8, 12, 14, EW (up to week 14))
- Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC)(Week 2, 4, 8, 12, 14, EW (up to week 14))
- Change From Baseline in Mean Corpuscle Hemoglobin (MCH)(Week 2, 4, 8, 12, 14, EW (up to week 14))
- Change From Baseline in Mean Corpuscle Volume (MCV)(Week 2, 4, 8, 12, 14, EW (up to week 14))
- Number of Participants With Immunopheotyping Data Outside the Reference Range(Baseline, Week, 4, 8, 12 and post-screen (up to Week 16))
- Change From Baseline in Erythrocyte Count(Weeks 2, 4, 8, 12, 14, EW (week up to 14))
- Number of Participants With Hematology Data of Potential Clinical Importance(Baseline, Week 2, 4, 8, 12, 14, early withdrawal, and post screen (up to Week 16))
- Number of Participants With Abnormal Electrocardiogram (ECG) Findings(Baseline, Week 1, 12, 14, EW ( up to Week 14), post-screen)
- Change From Baseline in Immunoglobin (Ig) A, IgG and IgM Levels(Week, 4, 8 and 12)
- Number of Participants With Immunoglobulin Data Outside the Reference Range(Baseline, Week, 4, 8, 12, post-screen (up to Week 16))