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

NCT ID: NCT02564055

Last Updated: 2017-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 247 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-01
• Study Completion Date: 2017-01-12

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.

Conditions

Dermatitis, Atopic

Keywords

Vehicle-Controlled; GSK2894512; Double blind; Dose-finding; Atopic Dermatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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).

Group Type: EXPERIMENTAL

GSK2894512 1% Cream

Intervention Type: 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

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).

Group Type: EXPERIMENTAL

GSK2894512 1% Cream

Intervention Type: DRUG

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

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).

Group Type: EXPERIMENTAL

GSK2894512 0.5% Cream

Intervention Type: 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

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).

Group Type: EXPERIMENTAL

GSK2894512 0.5% Cream

Intervention Type: DRUG

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

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).

Group Type: PLACEBO_COMPARATOR

Vehicle cream

Intervention Type: DRUG

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

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).

Group Type: PLACEBO_COMPARATOR

Vehicle cream

Intervention Type: DRUG

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

Interventions

GSK2894512 1% Cream

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

Intervention Type: DRUG

GSK2894512 0.5% Cream

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

Intervention Type: DRUG

Vehicle cream

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

Intervention Type: DRUG

Eligibility 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).

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Fort Smith, Arkansas, United States

GSK Investigational Site

Fresno, California, United States

GSK Investigational Site

Irvine, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Oceanside, California, United States

GSK Investigational Site

Santa Ana, California, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

North Logan, Connecticut, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

West Dundee, Illinois, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

New Albany, Indiana, United States

GSK Investigational Site

Overland Park, Kansas, United States

GSK Investigational Site

New Orleans, Louisiana, United States

GSK Investigational Site

Andover, Massachusetts, United States

GSK Investigational Site

Bay City, Michigan, United States

GSK Investigational Site

West Bloomfield, Michigan, United States

GSK Investigational Site

Fridley, Minnesota, United States

GSK Investigational Site

Saint Joseph, Missouri, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

High Point, North Carolina, United States

GSK Investigational Site

Cincinnati, Ohio, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Cranston, Rhode Island, United States

GSK Investigational Site

Greer, South Carolina, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Webster, Texas, United States

GSK Investigational Site

Norfolk, Virginia, United States

GSK Investigational Site

Seattle, Washington, United States

GSK Investigational Site

Surrey, British Columbia, Canada

GSK Investigational Site

Markham, Ontario, Canada

GSK Investigational Site

Oakville, Ontario, Canada

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Peterborough, Ontario, Canada

GSK Investigational Site

Richmond Hill, Ontario, Canada

GSK Investigational Site

Waterloo, Ontario, Canada

GSK Investigational Site

Windsor, Ontario, Canada

GSK Investigational Site

Drummondville, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kumamoto, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

Countries

United States; Canada; Japan

Other Identifiers

203121

Identifier Type: -

Identifier Source: org_study_id