Clinical trial NCT02564042: A Dose-Finding Study of GSK2894512 Cream in Subjects With Plaque Psoriasis
Official title: Study 203120: A Randomized, Blinded, Vehicle-Controlled, Dose-Finding Study of GSK2894512 Cream for the Treatment of Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis
Keywords: Double blind
Dose-finding
Vehicle-Controlled
GSK2894512
Plaque Psoriasis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-09-30
Enrollment: 227
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: 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
timeFrame: Baseline and up to Week 12
Secondary outcomes:
measure: Percentage of Participants With >=75 Percent Improvement in Psoriasis Area and Severity Index (PASI) From Baseline to Each Study Visit
timeFrame: Baseline and up to Week 16
measure: Percentage of Participants With a Minimum 2 Grade Improvement in PGA Score From Baseline to Each Study Visit
timeFrame: Baseline and up to Week 16
measure: Percentage of Participants With a PGA Score of 0 or 1 at Each Study Visit
timeFrame: Up to Week 16
measure: Mean Change in Percent of BSA Affected With Psoriasis From Baseline to Each Study Visit
timeFrame: Baseline and up to Week 16
measure: Mean Change in PASI Score From Baseline to Each Study Visit
timeFrame: Baseline and up to Week 16
measure: PGA Scores at Each Study Visit
timeFrame: Up to Week 16
measure: Mean Change in PGA Score From Baseline to Each Study Visit
timeFrame: Baseline and up to Week 16
measure: Mean Change in Individual Target Lesion Grading Scores From Baseline to Each Study Visit
timeFrame: Baseline and up to Week 16
measure: Mean Change in Weekly Average Itch/Pruritus Numeric Rating Scale (NRS) From Baseline to Each Study Visit
timeFrame: Baseline and up to Week 16
measure: Percentage of Participants Who Achieved a PGA Score of 0 or 1 and a Minimum 2 Grade Improvement From Baseline to Each Study Visit
timeFrame: Baseline and up to Week 16
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Up to Week 16
measure: Number of Participants With Reported Local Tolerability Scores
timeFrame: Up to Week 14
measure: Change From Baseline in Albumin and Protein Level
timeFrame: Baseline and up to Week 14
measure: Change From Baseline in Alkaline Phosphatase (Alk Phos), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Levels.
timeFrame: Baseline and up to Week 14
measure: Change From Baseline in Direct Bilirubin (Bil), Bilirubin (Bil), Creatinine and Urate.
timeFrame: Baseline and up to Week 14
measure: Change From Baseline in Calcium, Chloride, Carbon Dioxide (CO2), Glucose, Potassium, Sodium and Urea Levels
timeFrame: Baseline and up to Week 14
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocyte Count
timeFrame: Baseline and up to Week 14
measure: Change From Baseline in Hematocrit Levels
timeFrame: Baseline and up to Week 14
measure: Change From Baseline in Hemoglobin (Hgb) Level and Erythrocyte Mean Corpuscular Hgb Concentration (MCHC)
timeFrame: Baseline and up to Week 14
measure: Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin Level
timeFrame: Baseline and up to Week 14
measure: Change From Baseline in Erythrocyte Mean Corpuscular Volume
timeFrame: Baseline and up to Week 14
measure: Change From Baseline in Erythrocyte Count
timeFrame: Baseline and up to Week 14
measure: Number of Participants With Chemistry Data of Potential Clinical Importance
timeFrame: Up to Week 14
measure: Number of Participants With Hematology Data of Clinical Importance
timeFrame: Up to Week 14
measure: Change From Baseline in Immunoglobulin (Ig) A, IgG and IgM Levels
timeFrame: Baseline and up to Week 12
measure: Number of Participants With Ig Data Outside the Reference Range
timeFrame: Up to Week 12
measure: Number of Participants With Immunophenotyping Data Outside the Reference Range
timeFrame: Up to Week 12
measure: Change From Baseline in Immunophenotype Data
timeFrame: Baseline and up to Week 12
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Baseline and up to Week 14
measure: Change From Baseline in Pulse Rate
timeFrame: Baseline and up to Week 14
measure: Change From Baseline in Temperature
timeFrame: Baseline and up to Week 14
measure: Number of Participants With Vital Signs of Clinical Importance
timeFrame: Up to Week 14
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
timeFrame: Up to Week 14
Other outcomes:
Locations:
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: North Logan
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Plainfield
country: United States
facility: GSK Investigational Site
state: Indiana
city: Overland Park
country: United States
facility: GSK Investigational Site
state: Kansas
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Fort Gratiot Township
country: United States
facility: GSK Investigational Site
state: Michigan
city: High Point
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Johnston
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Goodlettsville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Webster
country: United States
facility: GSK Investigational Site
state: Texas
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Surrey
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Hamilton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Markham
country: Canada
facility: GSK Investigational Site
state: Ontario
city: North Bay
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Oakville
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Peterborough
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Richmond Hill
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Waterloo
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kumamoto
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: