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

NCT02564055 | Completed Phase 2 Results DMC

• 1 other identifier: 203121
• Study Type: interventional
• Target: 247
• Locations: 3 countries
• Sites: 60

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Have an Investigator Global Assessment (IGA) Score of Clear or Almost Clear (0 or 1) at Week 12 and a Minimum 2 Grade Improvement in IGA Score From Baseline to Week 12 for Intent to Treat (ITT) Population

  The IGA is a clinical tool for assessing the current state/severity of a participant's AD. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines. The percentage of participants who have an IGA score of clear or almost clear at Week 12 and a minimum 2 grade improvement from Baseline to Week 12 in IGA score was presented. . The analysis was performed on ITT Population which comprised of all randomized participants.

  Baseline and up to Week 12

Secondary Outcomes (39)

• Mean Change From Baseline in Weekly Average of Daily Itch/Pruritus (Numeric Rating Scale [NRS]) Score

  Baseline and up to Week 12

• Mean Percent Change From Baseline in Weekly Average of Daily Itch/Pruritus NRS Score

  Baseline and up to Week 12

• Percentage of Participants Who Achieve a Minimum 3- Point Improvement in Itch/Pruritus (NRS) From Baseline to Each Study Visit

  Week 1, 2, 4, 8, 12, 14, 16, early withdrawal (EW) (up to Week 16)

• Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score

  Week 1, 2, 4, 8, 12, 14, 16, EW (up to Week 16)

• Mean Percent Change From Baseline in EASI Score

  Weeks 1, 2, 4, 8, 12, 14, 16, EW (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 atopic dermatitis 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 atopic dermatitis 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 atopic dermatitis 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 atopic dermatitis 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 atopic dermatitis 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 atopic dermatitis 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: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (60)

GSK Investigational Site

Fort Smith, Arkansas, 72916, United States

Location

GSK Investigational Site

Fresno, California, 93720-2933, United States

Location

GSK Investigational Site

Irvine, California, 92697, United States

Location

GSK Investigational Site

Los Angeles, California, 90045, United States

Location

GSK Investigational Site

Oceanside, California, 92056, United States

Location

GSK Investigational Site

Santa Ana, California, 92701, United States

Location

GSK Investigational Site

Denver, Colorado, 80220, United States

Location

GSK Investigational Site

North Logan, Connecticut, 06032, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30342, United States

Location

GSK Investigational Site

Chicago, Illinois, 60611, United States

Location

GSK Investigational Site

West Dundee, Illinois, 60118, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46256, United States

Location

GSK Investigational Site

New Albany, Indiana, 47150, United States

Location

GSK Investigational Site

Overland Park, Kansas, 66215, United States

Location

GSK Investigational Site

New Orleans, Louisiana, 70115, United States

Location

GSK Investigational Site

Andover, Massachusetts, 01810, United States

Location

GSK Investigational Site

Bay City, Michigan, 48706, United States

Location

GSK Investigational Site

West Bloomfield, Michigan, 48322, United States

Location

GSK Investigational Site

Fridley, Minnesota, 55432, United States

Location

GSK Investigational Site

Saint Joseph, Missouri, 64506, United States

Location

GSK Investigational Site

New York, New York, 10022, United States

Location

GSK Investigational Site

High Point, North Carolina, 27262, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45255, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19103, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15213, United States

Location

GSK Investigational Site

Cranston, Rhode Island, 2910, United States

Location

GSK Investigational Site

Greer, South Carolina, 29650, United States

Location

GSK Investigational Site

Dallas, Texas, 75230, United States

Location

GSK Investigational Site

Dallas, Texas, 75231, United States

Location

GSK Investigational Site

Houston, Texas, 77004, United States

Location

GSK Investigational Site

Houston, Texas, 77056, United States

Location

GSK Investigational Site

San Antonio, Texas, 78218, 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

Norfolk, Virginia, 23507, 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

Markham, Ontario, L3P1X2, 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 5L7, Canada

Location

GSK Investigational Site

Drummondville, Quebec, J2B 5L4, 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, 003-0026, Japan

Location

GSK Investigational Site

Hokkaido, 006-0022, Japan

Location

GSK Investigational Site

Kanagawa, 211-0063, Japan

Location

GSK Investigational Site

Kanagawa, 220-0004, 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, 169-0075, Japan

Location

GSK Investigational Site

Tokyo, 194-0013, Japan

Location

GSK Investigational Site

Tokyo, 203-0003, Japan

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

tapinarof

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System 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: December 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: January 12, 2017
• Last Updated: November 20, 2017
• Results First Posted: November 20, 2017

Record last verified: 2017-08

Locations

JP (14); US (36); CA (10)