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



Status:Completed
Conditions:Dermatology, Dermatology, Dermatology
Therapuetic Areas:Dermatology / Plastic Surgery
Healthy:No
Age Range:12 - 65
Updated:11/22/2017
Start Date:December 1, 2015
End Date:January 12, 2017

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Study 203121: A Randomized, Blinded, Vehicle-Controlled, Dose-Finding Study of GSK2894512 Cream for the Treatment of Atopic Dermatitis

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.


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).
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