Study 203120: A Randomized, Blinded, Vehicle-Controlled, Dose-Finding Study of GSK2894512 Cream for the Treatment of Plaque Psoriasis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 227
- 试验地点
- 1
- 主要终点
- Percentage of Participants Who Have a Physician Global Assessment (PGA) Score of 0 or 1 at Week 12 and a Minimum 2-grade Improvement in PGA Score From Baseline to Week 12
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 subjects with plaque psoriasis. Results from this study will be considered when selecting the most appropriate concentration of GSK2894512 cream and dosing frequency in future clinical safety and efficacy studies. This is a multicenter (United States, Canada, and Japan), randomized, double-blind (sponsor-unblind), vehicle-controlled, 6-arm, parallel-group, dose-finding study. Two concentrations of GSK2894512 cream (0.5% and 1%) and a vehicle control cream will be equally randomized and evaluated following application to all psoriasis 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 adult males and females subjects with plaque psoriasis 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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female between 18 to 65 years of age inclusive, at the time of signing the informed consent.
- •Confirmed clinical diagnosis of chronic stable plaque psoriasis for >=6 months.
- •Body surface area involvement >=1% and <=15%, excluding scalp, at Screening and Baseline.
- •A PGA of psoriasis score >=2 at Baseline.
- •One target plaque located on the trunk or proximal parts of extremities (excluding knees, elbows, and intertriginous areas) that is at least 3 (centimetre) cm х 3 cm in size at Screening and Baseline with a severity representative of the subject's overall disease.
- •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 (at least five terminal half-lives OR until any continuing pharmacologic effect has ended, whichever is longer) after the last dose of study medication and completion of the follow-up visit.
排除标准
- •Any sign of infection of any of the psoriatic lesions.
- •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 the study treatment excipients, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation.
- •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, or positive hepatitis C antibody test result within 3 months of screening.
- •Liver function tests: alanine aminotransferase >=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 psoriasis.
- •Used any of the following treatments within the indicated washout period before the baseline visit: 1) 12 weeks or 5 half-lives (whichever is longer) - biologic agents (eg, 24 weeks for alefacept, 12 weeks for etanercept, 15 weeks for ustekinumab); 2) 12 weeks - oral retinoids (eg, acitretin or isotretinoin); 3) 8 weeks - cyclosporin, interferon, methotrexate, other systemic immunosuppressive or immunomodulating agents, or psoralen plus UVA light treatment; 4) 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogs; 5) 2 weeks - immunizations; drugs known to possibly worsen psoriasis, such as beta-blockers (eg, propranolol), lithium, iodides, angiotensin-converting enzyme inhibitors, and indomethacin, unless on a stable dose for >12 weeks; 6) 2 weeks - topical treatments: corticosteroids, immunomodulators, anthralin (dithranol), Vitamin D derivatives, retinoids, or coal tar (used on the body).
- •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
Vehicle cream twice daily
Subjects will apply a thin layer of vehicle topical cream twice daily (morning and evening) for 12 weeks, to all psoriasis lesions (except on the scalp).
干预措施: Vehicle cream (Drug)
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 psoriasis 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 psoriasis 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 psoriasis 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 psoriasis lesions (except on the scalp).
干预措施: GSK2894512 0.5% Cream (Drug)
Vehicle cream once daily
Subjects will apply a thin layer of vehicle topical cream once daily (evening) for 12 weeks, to all psoriasis 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 a Physician Global Assessment (PGA) Score of 0 or 1 at Week 12 and a Minimum 2-grade Improvement in PGA Score From Baseline to Week 12
时间窗: Baseline and up to Week 12
The PGA is a clinical tool for assessing the current state/severity of a participant's psoriasis. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, plaque thickness, and scaling as guidelines. Each assessment was made as a visual 'average' of the severity of all treated areas at the time of the assessment. The scores ranged from 0 to 4 where 0 = Clear, 1 = Almost Clear, 2 = Mild, 3 = Moderate and 4=Severe. The percentage of responders that is, participants who achieved a PGA score of 0 or 1 and a minimum 2-grade improvement from Baseline were summarized. Baseline was defined as the latest assessment prior to the first dose. The analysis was performed on modified intent-to-treat (mITT) Population which comprised of all randomized participants except those enrolled at center ID 220008.
次要结局
- Percentage of Participants With >=75 Percent Improvement in Psoriasis Area and Severity Index (PASI) From Baseline to Each Study Visit(Baseline and up to Week 16)
- Percentage of Participants With a Minimum 2 Grade Improvement in PGA Score From Baseline to Each Study Visit(Baseline and up to Week 16)
- Mean Change in PGA Score From Baseline to Each Study Visit(Baseline and up to Week 16)
- Mean Change in Weekly Average Itch/Pruritus Numeric Rating Scale (NRS) From Baseline to Each Study Visit(Baseline and up to Week 16)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs(Up to Week 16)
- Change From Baseline in Calcium, Chloride, Carbon Dioxide (CO2), Glucose, Potassium, Sodium and Urea Levels(Baseline and up to Week 14)
- Change From Baseline in Immunoglobulin (Ig) A, IgG and IgM Levels(Baseline and up to Week 12)
- Change From Baseline in Immunophenotype Data(Baseline and up to Week 12)
- Mean Change in PASI Score From Baseline to Each Study Visit(Baseline and up to Week 16)
- PGA Scores at Each Study Visit(Up to Week 16)
- Number of Participants With Reported Local Tolerability Scores(Up to Week 14)
- Change From Baseline in Albumin and Protein Level(Baseline and up to Week 14)
- Change From Baseline in Alkaline Phosphatase (Alk Phos), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Levels.(Baseline and up to Week 14)
- Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocyte Count(Baseline and up to Week 14)
- Change From Baseline in Hematocrit Levels(Baseline and up to Week 14)
- Percentage of Participants With a PGA Score of 0 or 1 at Each Study Visit(Up to Week 16)
- Change From Baseline in Hemoglobin (Hgb) Level and Erythrocyte Mean Corpuscular Hgb Concentration (MCHC)(Baseline and up to Week 14)
- Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin Level(Baseline and up to Week 14)
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Baseline and up to Week 14)
- Change From Baseline in Pulse Rate(Baseline and up to Week 14)
- Mean Change in Percent of BSA Affected With Psoriasis From Baseline to Each Study Visit(Baseline and up to Week 16)
- Change From Baseline in Direct Bilirubin (Bil), Bilirubin (Bil), Creatinine and Urate.(Baseline and up to Week 14)
- Number of Participants With Hematology Data of Clinical Importance(Up to Week 14)
- Change From Baseline in Temperature(Baseline and up to Week 14)
- Mean Change in Individual Target Lesion Grading Scores From Baseline to Each Study Visit(Baseline and up to Week 16)
- Percentage of Participants Who Achieved a PGA Score of 0 or 1 and a Minimum 2 Grade Improvement From Baseline to Each Study Visit(Baseline and up to Week 16)
- Change From Baseline in Erythrocyte Mean Corpuscular Volume(Baseline and up to Week 14)
- Number of Participants With Chemistry Data of Potential Clinical Importance(Up to Week 14)
- Number of Participants With Immunophenotyping Data Outside the Reference Range(Up to Week 12)
- Change From Baseline in Erythrocyte Count(Baseline and up to Week 14)
- Number of Participants With Ig Data Outside the Reference Range(Up to Week 12)
- Number of Participants With Vital Signs of Clinical Importance(Up to Week 14)
- Number of Participants With Abnormal Electrocardiogram (ECG) Findings(Up to Week 14)