Clinical trial NCT03004846: A Study of GSK2981278 Ointment in Subjects With Plaque Psoriasis
Official title: A Two-part Trial to Evaluate the Safety, Tolerability, Clinical Effect and Systemic Exposure Potential of Topically Applied GSK2981278 Ointment in Subjects With Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Psoriasis
Keywords: Vehicle- controlled
GSK2981278
Plaque psoriasis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-12-29
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: GSK2981278 is an inverse agonist of retinoic acid receptor-related orphan receptor (ROR) gamma. The aim of this study is to evaluate the safety, tolerability, clinical effect, and systemic exposure potential of topically applied GSK2981278 ointment in subjects with plaque psoriasis by treating all plaques on the body for 8 weeks. This single-center study will be conducted in two parts. Part A will be an open-label, single arm study and part B will be a double-blind, randomized, 2-arm, parallel-group, vehicle-controlled study. In Part A, 8 adult subjects and in Part B, 18 adult subjects with chronic stable plaque psoriasis will be enrolled. Total duration of study will be approximately 14 weeks. The results of this study will provide preliminary information about safety and efficacy of the drug and will help in providing the guidance for further development strategy.


Eligibility criteria: Inclusion Criteria:

* 18 years of age and above, at the time of signing the informed consent.
* Subjects with clinical diagnosis of stable plaque psoriasis for more than or equal to 6 months, as confirmed by the investigator.
* BSA involvement more than or equal to 5 percent and less than or equal to 15 percent, excluding face and intertriginous areas, at Screening and Baseline. The area of psoriasis involvement may include up to 2 percent of total BSA on the scalp with only sparse terminal hair and/or vellus hair.
* A PGA score of greater than or equal to 2 at Baseline.
* One target plaque located on the trunk or proximal parts of extremities (excluding scalp, knees, and elbows) that is at least 9 Centimeter \^2 in size at Screening and Baseline with a TPSS greater than or equal to 5 and induration sub score greater than or equal to 2.
* Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 2 weeks after the last dose of study medication: a) Vasectomy with documentation of azoospermia. The documentation on male sterility can come from the site personnel's: review of subject's medical records, medical examination and/or semen analysis, or medical history interview. B) Male condom. The allowed method of contraception is only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
* Female of non-reproductive potential (FNRP) is eligible to participate in this study if she meets at least one of the following conditions: a) Females with one of the following procedures documented and no plans to utilize assisted reproductive techniques (e.g., in vitro fertilization or donor embryo transfer): bilateral tubal ligation or salpingectomy, hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy, bilateral Oophorectomy (surgical menopause); b) Post-menopausal women including Females 60 years of age or older, A practical definition accepts menopause after 1 year without menses with an appropriate clinical profile, e.g., age appropriate, more than 45 years, in the absence of hormone replacement therapy (HRT) or medical suppression of the menstrual cycle (e.g., leuprolide treatment). In questionable cases for women less than 60 years of age, a blood sample with simultaneous follicle stimulating hormone and estradiol falling into the central laboratory's post-menopausal reference range is confirmatory (these levels need to be adjusted for specific laboratories/assays. Females fewer than 60 years of age, who are on HRT and wish to continue, and whose menopausal status is in doubt, should not be enrolled in this study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can enroll into the study and resume use of HRT.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

Exclusion Criteria:

* Psoriasis other than plaque variant (i.e. acute psoriasis guttate, psoriasis punctata, psoriasis erythroderma or pustular psoriasis).
* Current evidence of another ongoing or any acute cutaneous infection, history of repeated or chronic significant skin infections (unless irrelevant in the opinion of the investigator, i.e. onychomycosis, labial herpes or other minor diagnosis).
* Clinically-relevant skin disease or other skin pathologies, that may, in the opinion of the investigator, contraindicate participation or interfere with skin evaluations.
* ALT more than 2x Upper limit of normal (ULN) and bilirubin more than 1.5x ULN (isolated bilirubin more than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percent).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Corrected QT interval using Bazett's formula (QTcB) more than 450 milliseconds (msec) or QTcB more than 480 msec in subjects with Bundle Branch Block. The QTcB should be based on single QTcB values of ECG obtained over a brief recording period. If QTcB is outside the threshold value, triplicate ECGs may be performed with the QTcB values averaged.
* Any condition that, in the judgment of the investigator, would put the subject at un-acceptable risk for the participation in the trial.
* History of malignancy within 5 years prior to dosing, except adequately treated non-invasive cancer of the skin (basal or squamous cell).
* Use of prohibited concomitant medications or products within the defined periods before the Day 1 visit and during the trial
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
* Symptoms of a clinically significant illness that may, in the opinion of the investigator, influence the outcome of the trial in the 4 weeks before baseline visit and during the trial.
* Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
* A positive pre-study drug/alcohol screen.
* A positive test for human immunodeficiency virus (HIV) antibody.
* For Part B only-the subject has participated in Part A of this study.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 4 weeks, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Prolonged exposure to natural or artificial sources of ultraviolet (UV) radiation (e.g., exposure to sunlight other than that associated with usual daily activities, use of tanning booth, etc.) within 2 weeks prior to the Day 1 visit or intention to have such exposure during the study, thought by the investigator likely to modify the subject's psoriasis.
* In the opinion of the investigator or physician performing the initial examination the subject should not participate in the clinical trial, e.g. due to probable noncompliance, inability to understand the trial and give adequately informed consent, or inability to complete the Psoriasis Symptom Diary.
* Close affiliation with the investigator (e.g. a close relative) or persons working at bioskin GmbH or subject is an employee of sponsor.
* Subject is institutionalized because of legal or regulatory order.

Primary outcomes:
measure: Number of Participants With On-treatment Serious Adverse Events (SAEs) and Non-SAEs: Part A
timeFrame: Up to Day 57
measure: Number of Participants With Application Site Tolerability Assessment Score During Treatment Period: Part A
timeFrame: Day 1, Day 15, Day 29, Day 57
measure: Number of Participants With Negative Urinalysis Results: Part A
timeFrame: Up to Day 57
measure: Change From Baseline in Potential of Hydrogen (pH) of Urine: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Specific Gravity of Urine: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Blood Urea Nitrogen (BUN), Glucose, Potassium, Sodium and Calcium Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Creatinine, Total and Direct Bilirubin Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Protein and Albumin Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Platelet, Leukocyte, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Erythrocyte Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Hemoglobin Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Hematocrit Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Mean Corpuscular Volume (MCV) Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Pulse Rate Levels: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in Electrocardiogram (ECG) Parameters Including Single RR Heart Rate: Part A
timeFrame: Baseline and up to Day 57
measure: Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB) and RR Interval: Part A
timeFrame: Baseline and up to Day 57
measure: Plasma Concentration of GSK2981278 at Nominal Time: Part A
timeFrame: Pre-dose, 1, 2, 4, 6, 8, 10 hours post-dose on Day 1, Day 29 and Day 57; Pre-dose, 2 hours post-dose on Day 15
measure: Number of Participants With SAEs and Non-SAEs: Part B
timeFrame: Up to Day 57
measure: Number of Participants With Application Site Tolerability Assessment Score During Treatment Period: Part B
timeFrame: Up to Day 57
measure: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline: Part B
timeFrame: Baseline and up to Week 57
measure: Number of Participants With Change in Hematology Toxicity Grade From Baseline: Part B
timeFrame: Baseline and up to Day 57
measure: Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug: Part B
timeFrame: Up to Day 57
measure: Number of Participants With Abnormal Findings for ECG Parameters: Part B
timeFrame: Up to Day 57
measure: Mean Percent Change in TPSS From Baseline to Week 8: Part B
timeFrame: Baseline and up to Week 8
measure: Mean Percent Change in PGA Score From Baseline to Week 8: Part B
timeFrame: Baseline and up to Week 8
measure: Mean Percent Change in PASI From Baseline to Week 8: Part B
timeFrame: Baseline and up to Week 8
Secondary outcomes:
measure: Mean Percent Change From Baseline in Target Plaque Severity Score (TPSS): Part A
timeFrame: Baseline and up to Week 8
measure: Mean Percent Change From Baseline in Physician's Global Assessment (PGA) Score: Part A
timeFrame: Baseline and up to Week 8
measure: Mean Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score: Part A
timeFrame: Baseline and up to Week 8
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
affiliation: GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: