A Dose-Finding Study of GSK2894512 Cream in Subjects With Atopic Dermatitis (AD)
Condition: Dermatitis, Atopic
MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema
Intervention: GSK2894512 1% Cream; GSK2894512 0.5% Cream; Vehicle cream
Intervention description: 1.0% (10 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically; 0.5% (5 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically; White to off-white vehicle cream base to be applied topically
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 247.0
Sex: All
Minimum age: 12 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Vehicle-Controlled; GSK2894512; Double blind; Dose-finding; Atopic Dermatitis

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.
    

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).