| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| E.1.2 | System Organ Class | 100000004858 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Part A
-To evaluate the safety and tolerability of topically applied GSK2981278 in subjects with plaque psoriasis
-To evaluate the systemic exposure of
GSK2981278 following topical application in subjects with plaque psoriasis
Part B
-To evaluate the safety and tolerability of topically applied GSK2981278 and its
vehicle in subjects with plaque psoriasis
-To evaluate the clinical effect of topically applied GSK2981278 relative to vehicle control in subjects with plaque psoriasis |
|
| E.2.2 | Secondary objectives of the trial |
-Part A
To evaluate the clinical effect following
topical application of GSK2981278 in
subjects with plaque psoriasis
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
AGE
1. 18 years of age and above, at the time of signing the informed consent.
TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
2. Subjects with clinical diagnosis of stable plaque psoriasis for >or= 6 months, as confirmed by the investigator.
3. Body surface area involvement >or= 5% and <or= 15%, excluding face and intertriginous areas, at Screening and Baseline. The area of psoriasis involvement may include up to 2% of total BSA on the scalp with only sparse terminal hair and/or vellus hair.
4. A PGA score of >or= 2 at Baseline
5. One target plaque located on the trunk or proximal parts of extremities (excluding scalp, knees, and elbows) that is at least 9 cm2 in size at Screening and Baseline with a Target Plaque Severity Score (TPSS) >or= 5 and induration subscore >or= 2.
SEX
6. Male
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.
7. Female of non-reproductive potential (FNRP)
A 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 all women over 60 years of age, see below),
Post-Menopause criteria
- 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, >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 <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) [Kronenberg,
2008; Strauss, 2004].
- Females under 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 postmenopausal 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 enrol into the study and resume use of HRT.
INFORMED CONSENT
8. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. |
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| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER FUNCTION AND QTc INTERVAL)
1. Psoriasis other than plaque variant (i.e. acute psoriasis guttate, psoriasis punctata, psoriasis erythroderma or pustular psoriasis).
2. 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).
3. Clinically-relevant skin disease or other skin pathologies, that may, in the opinion of the investigator, contraindicate participation or interfere with skin evaluations.
4. Alanine aminotransferase (ALT) >2xULN and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
5. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
6. QTcB >450 msec or QTcB >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.
7. Any condition that, in the judgement of the investigator, would put the subject at unacceptable risk for the participation in the trial.
8. History of malignancy within 5 years prior to dosing, except adequately treated noninvasive cancer of the skin (basal or squamous cell).
CONCOMITANT MEDICATIONS
9. Use of prohibited concomitant medications or products within the defined periods before the Day 1 visit and during the trial.
CONTRAINDICATIONS
10. 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.
11. 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.
DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
12. 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.
13. A positive pre-study drug/alcohol screen.
14. A positive test for human immunodeficiency virus (HIV) antibody.
15. For Part B only-the subject has participated in Part A of this study.
16. 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).
17. 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.
18. 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.
19. Close affiliation with the investigator (e.g. a close relative) or persons working at bioskin GmbH or subject is an employee of sponsor.
20. Subject is institutionalized because of legal or regulatory order. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Part A:
•Incidence and nature of adverse events (AEs) and serious adverse events (SAEs)
•Application site tolerability assessment score
•Change in clinical laboratory parameters, vital signs, and electrocardiogram (ECG) from baseline
•Plasma concentrations of GSK2981278
Part B:
•Incidence and nature of AEs and SAEs
•Application site tolerability assessment score
•Change in clinical laboratory parameters, vital signs, and ECG from baseline
•Mean percent change in TPSS from baseline to Week 8
•Mean percent change in PGA score from baseline to Week 8
•Mean percent change in PASI from baseline to Week 8
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
English Part A
-AEs/SAEs: Assessed throughout the study, reviewed at day 1, 8, 15, 29, 43, 57
-Application site tolerability assessment score, laboratory parameters, vital signs and plasma concentrations: Day 1(Baseline), day 15, day 29 and day 57
-ECGs: Day 1(Baseline), day 29 and day 57
Part B
-AEs/SAEs: Assessed throughout the study, reviewed at day 1,8, 15, 29, 43, 57
-Application site tolerability assessment score, laboratory parameters, and vital signs: Day 1(Baseline), day 15, day 29 and day 57
-ECGs: Day 1(Baseline), day 29 and day 57
|
|
| E.5.2 | Secondary end point(s) |
Part A:
•Mean percent change in Target Plaque Severity Score (TPSS) from baseline to Week 8
•Mean percent change in Physician’s Global Assessment (PGA) score from baseline to Week 8
•Mean percent change in Psoriasis Area and Severity Index (PASI) from baseline to Week 8
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Part A
-Day 1(Baseline), day 15, day 29 and day 57
-Day 1(Baseline), day 15, day 29 and day 57
-Day 1(Baseline), day 15, day 29 and day 57 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| safety and tolerability in patients |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Part A: open label, single arm - Part B: double-blind, randomized, 2-arm, parallel-group, Placebo |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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