A Dose-Finding Study of GSK2894512 Cream in Subjects With Plaque Psoriasis

NCT02564042 | Completed Phase 2 Results DMC

• 1 other identifier: 203120
• Study Type: interventional
• Target: 227
• Locations: 3 countries
• Sites: 46

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.

Conditions

Psoriasis

Keywords

Double blind; Dose-finding; Vehicle-Controlled; GSK2894512; Plaque Psoriasis

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  Baseline and up to Week 12

Secondary Outcomes (33)

• 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

• Percentage of Participants With a PGA Score of 0 or 1 at Each Study Visit

  Up to Week 16

• Mean Change in Percent of BSA Affected With Psoriasis From Baseline to Each Study Visit

  Baseline and up to Week 16

• Mean Change in PASI Score From Baseline to Each Study Visit

  Baseline and up to Week 16

Study Arms (6)

GSK2894512 1% cream twice daily

EXPERIMENTAL

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).

Drug: GSK2894512 1% Cream

GSK2894512 1% cream once daily

EXPERIMENTAL

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).

Drug: GSK2894512 1% Cream

GSK2894512 0.5% cream twice daily

EXPERIMENTAL

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).

Drug: GSK2894512 0.5% Cream

GSK2894512 0.5% cream once daily

EXPERIMENTAL

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).

Drug: GSK2894512 0.5% Cream

Vehicle cream twice daily

PLACEBO COMPARATOR

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).

Drug: Vehicle cream

Vehicle cream once daily

PLACEBO COMPARATOR

Subjects will apply a thin layer of vehicle topical cream once daily (evening) for 12 weeks, to all psoriasis lesions (except on the scalp).

Drug: Vehicle cream

Interventions

GSK2894512 1% Cream DRUG

1.0% (10 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically

GSK2894512 1% cream once daily; GSK2894512 1% cream twice daily

GSK2894512 0.5% Cream DRUG

0.5% (5 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically

GSK2894512 0.5% cream once daily; GSK2894512 0.5% cream twice daily

Vehicle cream DRUG

White to off-white vehicle cream base to be applied topically

Vehicle cream once daily; Vehicle cream twice daily

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (46)

GSK Investigational Site

San Diego, California, 92123, United States

Location

GSK Investigational Site

North Logan, Connecticut, 06032, United States

Location

GSK Investigational Site

Miami, Florida, 33142, United States

Location

GSK Investigational Site

Chicago, Illinois, 60612, United States

Location

GSK Investigational Site

Plainfield, Indiana, 46168, United States

Location

GSK Investigational Site

Overland Park, Kansas, 66215, United States

Location

GSK Investigational Site

Louisville, Kentucky, 40217, United States

Location

GSK Investigational Site

Fort Gratiot Township, Michigan, 48059, United States

Location

GSK Investigational Site

High Point, North Carolina, 27262, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19103, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15213, United States

Location

GSK Investigational Site

Johnston, Rhode Island, 02919, United States

Location

GSK Investigational Site

Goodlettsville, Tennessee, 37072, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Houston, Texas, 77004, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Webster, Texas, 77598, United States

Location

GSK Investigational Site

Seattle, Washington, 98101, United States

Location

GSK Investigational Site

Surrey, British Columbia, V3R 6A7, Canada

Location

GSK Investigational Site

Hamilton, Ontario, L8N 1V6, Canada

Location

GSK Investigational Site

Markham, Ontario, L3P1X2, Canada

Location

GSK Investigational Site

North Bay, Ontario, P1B 3Z7, Canada

Location

GSK Investigational Site

Oakville, Ontario, L6J 7W5, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K2G 6E2, Canada

Location

GSK Investigational Site

Peterborough, Ontario, K9J5K2, Canada

Location

GSK Investigational Site

Richmond Hill, Ontario, L4B 1A5, Canada

Location

GSK Investigational Site

Waterloo, Ontario, N2J 1C4, Canada

Location

GSK Investigational Site

Windsor, Ontario, N8W 1E6, Canada

Location

GSK Investigational Site

Windsor, Ontario, N8W 5L7, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2K 4L5, Canada

Location

GSK Investigational Site

Québec, Quebec, G1V4X7, Canada

Location

GSK Investigational Site

Fukuoka, 813-0044, Japan

Location

GSK Investigational Site

Fukuoka, 819-0373, Japan

Location

GSK Investigational Site

Hokkaido, 006-0022, Japan

Location

GSK Investigational Site

Hokkaido, 066-0021, Japan

Location

GSK Investigational Site

Hokkaido, 066-0064, Japan

Location

GSK Investigational Site

Kanagawa, 221-0825, Japan

Location

GSK Investigational Site

Kumamoto, 861-3101, Japan

Location

GSK Investigational Site

Osaka, 572-0838, Japan

Location

GSK Investigational Site

Osaka, 593-8324, Japan

Location

GSK Investigational Site

Tokyo, 133-0057, Japan

Location

GSK Investigational Site

Tokyo, 136-0074, Japan

Location

GSK Investigational Site

Tokyo, 190-0023, Japan

Location

GSK Investigational Site

Tokyo, 194-0013, Japan

Location

GSK Investigational Site

Tokyo, 195-0053, Japan

Location

GSK Investigational Site

Tokyo, 203-0003, Japan

Location

MeSH Terms

Conditions

Psoriasis

Interventions

tapinarof

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2015
• First Posted: September 30, 2015
• Study Start: November 23, 2015
• Primary Completion: October 1, 2016
• Study Completion: October 5, 2016
• Last Updated: November 13, 2017
• Results First Posted: November 13, 2017

Record last verified: 2017-10

Locations

US (18); CA (13); JP (15)