Safety, Tolerability, Pharmacokinetics, Pharmacodynamics... | NCT02927457

ID	Type	Description	Link
2016-000277-20	EudraCT Number

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group A1- Skin Sites A/C/D (A/P/A)	Experimental	Skin areas A to E in group A are identified skin areas across the back of the subject. Subjects will be receiving GSK2646264 1% (A) for Area A- PV lesion, Placebo (P) for Area C- PV lesion and GSK2646264 1% for Area D- uninvolved skin once daily for 28 days according to randomisation. Skin areas B- PV lesion and E- uninvolved skin will not be assigned any treatment and will be used for the baseline biopsy.	Drug: GSK2646264 1% Drug: Placebo
Group A2- Skin Sites A/C/D (A/P/P)	Experimental	Skin areas A to E in group A are identified skin areas across the back of the subject. Subjects will be receiving GSK2646264 1% for Area A- PV lesion, Placebo for Area C- PV lesion and Placebo for Area D- uninvolved skin once daily for 28 days according to randomisation. Skin areas B- PV lesion and E- uninvolved skin will not be assigned any treatment and will be used for the baseline biopsy.	Drug: GSK2646264 1% Drug: Placebo
Group A3- Skin Sites A/C/D (P/A/A)	Experimental	Skin areas A to E in group A are identified skin areas across the back of the subject. Subjects will be receiving Placebo for Area A- PV lesion, GSK2646264 1% for Area C- PV lesion and GSK2646264 1% for Area D- uninvolved skin once daily for 28 days according to randomisation. Skin areas B- PV lesion and E- uninvolved skin will not be assigned any treatment and will be used for the baseline biopsy.	Drug: GSK2646264 1% Drug: Placebo
Group A4- Skin Sites A/C/D (P/A/P)	Experimental

Interventions

Name	Type	Description	Arm Group Labels	Other Names
GSK2646264 1%	Drug	A cream for topical application with a concentration of 1% GSK2646264.	Group A1- Skin Sites A/C/D (A/P/A) Group A2- Skin Sites A/C/D (A/P/P)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Emergent Chemistry Results by Potential Clinical Importance (PCI) Criteria	Blood samples were collected to analyze the clinical chemistry parameters; albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), calcium, glucose, potassium (Pot) and sodium. PCI ranges were albumin (low: <30 grams per liter), calcium (low: <2 millimoles per liter [mmol/L] and high: >2.75 mmol/L), glucose (low: <3 mmol/L and high: >9 mmol/L), Pot (low: <3 mmol/L and high: >5.5 mmol/L), sodium (low: <130 mmol/L and high: >150 mmol/L), ALT (high: >=2 times upper limit of normal [ULN] units per liter {U/L}), AST (high: >=2 times ULN U/L), ALP (high: >=2 times ULN U/L) and TB (high: >=1.5 times ULN micromoles per liter). Safety Population comprised of all participants who received at least one dose of study treatment. All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined.	Day 14, Day 28 and follow-up (up to Day 56)
Number of Participants With Emergent Hematology Results by PCI Criteria	PCI ranges were hematocrit [Hct] (high: >0.54 proportion of red blood cell [RBC] in blood), hemoglobin [Hb] (high: >180 grams per liter), RBC (low: <4.2x10^12 cells per liter and high: >5.9x10^12 cells per liter), lymphocytes [Lympho] (low: <0.8x10^9 cells per liter), monocytes [Mono] (low: <0.14x10^9 cells per liter and high: >1.3x10^9 cells per liter), neutrophils [Neutro] (low: <1.5x10^9 cells per liter), platelet count [PC] (low: <100x10^9 cells per liter and high: >550x10^9 cells per liter), eosinophils [Eos] (high: >0.55x10^9 cells per liter), basophils [Baso] (high: >0.22x10^9 cells per liter), white blood cell [WBC] (low: <3x10^9 cells per liter and high: >20x10^9 cells per liter). All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined.	Day 14, Day 28 and follow-up (up to Day 56)
Change From Baseline in Urine Potential of Hydrogen (pH)	Urine samples were collected to monitor the pH. pH is a measure of hydrogen ion concentration and is used to determine the acidity or alkalinity of urine. pH scale ranges from 0 to 14. A neutral pH is 7.0. The higher number indicates the more basic (alkaline) nature of urine and lower number indicates the more acidic urine. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined.

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Erythema, Scaling Hyperkeratosis, Edema/Infiltration, Dyspigmentation, Modified Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) Activity Score and Overall RCLASI Modified Score.	The score ranges for different components were; erythema [0 (absent) to 3 (dark red, purple/violaceous/crusted/hemorrhagic)], scaling/hyperkeratosis [0 (absent) to 2 (verrucous hyperkeratosis)], edema/infiltration [0 (absent) to 2 (palpable and visible)] and dyspigmentation [0 (absent) to 2 (hypo and hyper pigmentation)]. For all components, 0 (better) and 3 (worse). Modified RCLASI activity score was derived by adding score for erythema, scaling hyperkeratosis and edema/infiltration. Modified change from Baseline ranged from -7 to 7, 0 (no change), minus (better) and positive (worse). Overall RCLASI modified score was derived by summing the activity and dyspigmentation scores. Overall change from Baseline ranged from -9 to 9, 0 (no change), minus (better) and positive (worse). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data was not collected for Group A as no participants were dosed.

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Between 18 and 70 years of age inclusive, at the time of signing the informed consent.
Subject values for the following parameters thyroid-stimulating hormone (TSH), free thyroxine (T4), and free triiodothyronine (T3) within the normal range.
Subject has confirmed diagnosis of Lupus Erythematosus Tumidus (LET) (group A only), subacute or chronic CLE as determined by the investigators.
Body weight >= 50 kg and body mass index (BMI) within the range 19.9 - 35 kilogram (kg)/meter square (m^2) (inclusive)
Male OR Female.

Females: Non-reproductive potential defined as:

Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion , Hysterectomy, Documented Bilateral Oophorectomy
Postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be 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 (FRP) from 28 days prior to the first dose of study medication and until 12 days after the last dose of study medication and completion of the follow-up visit.

Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
All subjects must be free from scarring or skin markings (e.g. tattoos or piercings) and open wounds on the defined areas of the body that cream will be applied onto or that will be exposed to PV, unless in the opinion of the investigator it will not compromise the subjects' safety and quality of data.
Able to refrain from exposure to extended and direct sunlight during the study period, from screening until follow up, especially the area that is under treatment during the study.
Able to refrain from using self-tanning products on the areas on which the study cream will be applied for the duration of the study from screening to follow-up.
Able to refrain from shaving and waxing the areas on which the study cream will be applied during the duration of the study from screening to follow up.
Patient stable on either no treatment or on :
- Corticosteroids (=<7.5milligram [mg]/day prednisone or prednisone equivalent or less) for a minimum of 30 days prior to screening and through to Day 28.
- and /or hydroxychloroquine (=<400mg daily dose) for a minimum of 60 days prior to the initial photoprovocation for group A or Randomisation Visit for group B through to day 28.
- Topical steroids applied to the defined areas of the body that are not exposed to photoprovocation or study cream from screening to Day 28.
- Topical calcineurin inhibitors and retinoids applied to the defined areas of the body that are not exposed to photoprovocation or study cream from screening to Day 28.

Exclusion Criteria

ALT >2xupper limit of normal (ULN);
Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
QTcF > 450 millisecond (msec), or QTcF > 480 msec in subjects with Bundle Branch Block
History of any past or present benign or malignant skin conditions and disease, unless in the opinion of the investigator it will not compromise the subjects safety and quality of data.
Subjects with a history of Graves disease
Subjects with a history of thyroid cancer.
Unable to refrain from vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half lives (whichever is longer) prior to the screening visit until the completion of the follow-up assessments, unless in the opinion of the Investigator, in consultation with the GlaxoSmithKline (GSK) Medical Monitor if required, the medication will not interfere with the study procedures or compromise subject safety.
Clinically significant abnormality in the hematological, clinical chemistry, or urinalysis screen, as judged by the investigator after discussion with the medical monitor.
Subjects who start prohibited medications or therapies at any time during the study may be withdrawn from the study. Subjects who start prohibited medications or therapies may remain in the study only with the approval of the Medical Monitor and at the discretion of the Sponsor.
The following medications and therapies are prohibited at any time during the study:
- Use of other investigational agents (biologic or non-biologic; investigational applies to any drug not approved for sale in the country in which it is used).
- Co-enrolment into another study of an investigational agent or non-drug therapy.
- Use of biological agents (e.g., alemtuzumab [ATG], rituximab,) during the clinical study or within 12 months to first dose of study treatment.
- Use of other immunosuppressive drugs commonly used in Systemic lupus erythematosus (SLE) including Azathioprine, Methotrexate, Mycophenolate, Cyclophosphamide within 3 months to first dose of study treatment.
History of regular alcohol consumption within 3 months of the study defined as:

Alcohol will be allowed but limited to an average weekly intake of <21 units for males or <14 units for females).

Direct exposure to ultraviolet (UV) light (e.g. sunbathing) to the testing areas within 2 weeks of study entry.
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 (refer to the Investigator Brochure for a list of excipients).
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 screen.
Where participation in the study would result in donation of blood or blood products in excess of 450 milliliter (ml) within 3 months.
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: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.

Country Specific Exclusion criteria wording for Germany:

Subjects that are employees of either GlaxoSmithKline (sponsor) or one of the study centres (investigators).
Subjects who live in detention on court order or on regulatory action.
Oral Prednisolone
- Greater than 7.5 mg by mouth daily.
- Any increase in dose from screening to Day 28
Hydroxychloroquine
- Greater than 400 mg oral daily.
- Any increase in dose from screening to Day 28.
Photosensitizing drugs within 5 half-lives prior to the photoprovocation visit.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Tübingen	Baden-Wurttemberg	72076	Germany
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
33336508	Derived	Walker A, Erwig L, Foster K, Nevin K, Wenzel J, Worm M, Williams N, Ratia N, Hoang B, Schneider-Merck T, Gisbert S, Carnarius H, Dickson M. Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study. Exp Dermatol. 2021 Nov;30(11):1686-1692. doi: 10.1111/exd.14253. Epub 2020 Dec 17.

ID	Title	Description
FG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Jun 28, 2018	Apr 4, 2019

ID	Title	Description
BG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.
BG001	Group B- Participants With Natural Lesions	Participants with natural lesions were topically administered white to off-white aqueous cream of GSK2646264 (1% w/w) and placebo. The treatments were administered at the same time on different skin sites once daily for 28 days.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0000 BG00111 BG00211

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Emergent Chemistry Results by Potential Clinical Importance (PCI) Criteria

Blood samples were collected to analyze the clinical chemistry parameters; albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), calcium, glucose, potassium (Pot) and sodium. PCI ranges were albumin (low: <30 grams per liter), calcium (low: <2 millimoles per liter [mmol/L] and high: >2.75 mmol/L), glucose (low: <3 mmol/L and high: >9 mmol/L), Pot (low: <3 mmol/L and high: >5.5 mmol/L), sodium (low: <130 mmol/L and high: >150 mmol/L), ALT (high: >=2 times upper limit of normal [ULN] units per liter {U/L}), AST (high: >=2 times ULN U/L), ALP (high: >=2 times ULN U/L) and TB (high: >=1.5 times ULN micromoles per liter). Safety Population comprised of all participants who received at least one dose of study treatment. All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). Data was not collected for Group A as no participants were dosed.

Posted

Count of Participants

Participants

Day 14, Day 28 and follow-up (up to Day 56)

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.
OG001	Group B-Participants With Natural Lesions	Participants with natural lesions were topically administered white to off-white aqueous cream of GSK2646264 (1% w/w) and placebo. The treatments were administered at the same time on different skin sites once daily for 28 days.

Units	Counts
Participants	OG0000 OG00111

Title

Denominators

Categories

Albumin, Day 14, To low, n=0,11

- ParticipantsOG0000
- ParticipantsOG00111

Title	Measurements
	OG0010

Primary

Number of Participants With Emergent Hematology Results by PCI Criteria

PCI ranges were hematocrit [Hct] (high: >0.54 proportion of red blood cell [RBC] in blood), hemoglobin [Hb] (high: >180 grams per liter), RBC (low: <4.2x10^12 cells per liter and high: >5.9x10^12 cells per liter), lymphocytes [Lympho] (low: <0.8x10^9 cells per liter), monocytes [Mono] (low: <0.14x10^9 cells per liter and high: >1.3x10^9 cells per liter), neutrophils [Neutro] (low: <1.5x10^9 cells per liter), platelet count [PC] (low: <100x10^9 cells per liter and high: >550x10^9 cells per liter), eosinophils [Eos] (high: >0.55x10^9 cells per liter), basophils [Baso] (high: >0.22x10^9 cells per liter), white blood cell [WBC] (low: <3x10^9 cells per liter and high: >20x10^9 cells per liter). All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined.

Posted

Count of Participants

Participants

Day 14, Day 28 and follow-up (up to Day 56)

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.

Primary

Change From Baseline in Urine Potential of Hydrogen (pH)

Urine samples were collected to monitor the pH. pH is a measure of hydrogen ion concentration and is used to determine the acidity or alkalinity of urine. pH scale ranges from 0 to 14. A neutral pH is 7.0. The higher number indicates the more basic (alkaline) nature of urine and lower number indicates the more acidic urine. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined.

Posted

Mean

Standard Deviation

Baseline (Day 1), Day 14, Day 28 and follow-up (up to Day 56)

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.
OG001	Group B-Participants With Natural Lesions

Primary

Change From Baseline in Urine Specific Gravity

Urine samples were collected to monitor the specific gravity. Specific gravity is a measure of urine concentration and is measured using a chemical test. Specific gravity measurements provide a comparison of the amount of substances dissolved in urine as compared to pure water. If there were no solutes present, the specific gravity of urine would be 1.000 the same as pure water. Specific gravity between 1.002 and 1.035 could be considered as normal. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined.

Posted

Mean

Standard Deviation

kilogram per meter cube

Baseline (Day 1), Day 14, Day 28 and follow-up (up to Day 56)

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.
OG001

Primary

Number of Participants With Emergent Vital Sign Results by PCI Criteria

Vital signs such as diastolic blood pressure (DBP), heart rate (HR) and systolic blood pressure (SBP) were measured in semi-supine position after 5 minutes rest for the participants. PCI ranges were SBP (lower: <85 millimeters of mercury [mmHg] and upper: >160 mmHg), DBP: (lower: <45 mmHg and upper: >100 mmHg) and HR (lower: <40 beats per minute [bpm] and upper: >110 bpm). All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined.

Posted

Count of Participants

Participants

Day 14 and Day 28

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.
OG001	Group B-Participants With Natural Lesions	Participants with natural lesions were topically administered white to off-white aqueous cream of GSK2646264 (1% w/w) and placebo. The treatments were administered at the same time on different skin sites once daily for 28 days.

Primary

Change From Baseline in Electrocardiogram (ECG); HR

Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined.

Posted

Mean

Standard Deviation

bpm

Baseline (Day 1), Day 14 and follow-up (up to Day 56)

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.
OG001	Group B-Participants With Natural Lesions	Participants with natural lesions were topically administered white to off-white aqueous cream of GSK2646264 (1% w/w) and placebo. The treatments were administered at the same time on different skin sites once daily for 28 days.

Primary

Change From Baseline in ECG; PR Interval, QRS Duration, QT Interval and QTcF

Triplicate 12-lead ECGs were obtained using an ECG machine that automatically measured PR, QRS, QT, and QT interval corrected using Fridericia's formula (QTcF) intervals. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined.

Posted

Mean

Standard Deviation

Milliseconds

Baseline (Day 1), Day 14 and follow-up (up to Day 56)

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.
OG001	Group B-Participants With Natural Lesions	Participants with natural lesions were topically administered white to off-white aqueous cream of GSK2646264 (1% w/w) and placebo. The treatments were administered at the same time on different skin sites once daily for 28 days.

Primary

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement or events associated with liver injury and impaired liver function.

Safety Population. All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined. Data was not collected for Group A as no participants were dosed.

Posted

Count of Participants

Participants

Up to Day 56

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.
OG001	Group B-Participants With Natural Lesions

Secondary

Change From Baseline in Erythema, Scaling Hyperkeratosis, Edema/Infiltration, Dyspigmentation, Modified Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) Activity Score and Overall RCLASI Modified Score.

The score ranges for different components were; erythema [0 (absent) to 3 (dark red, purple/violaceous/crusted/hemorrhagic)], scaling/hyperkeratosis [0 (absent) to 2 (verrucous hyperkeratosis)], edema/infiltration [0 (absent) to 2 (palpable and visible)] and dyspigmentation [0 (absent) to 2 (hypo and hyper pigmentation)]. For all components, 0 (better) and 3 (worse). Modified RCLASI activity score was derived by adding score for erythema, scaling hyperkeratosis and edema/infiltration. Modified change from Baseline ranged from -7 to 7, 0 (no change), minus (better) and positive (worse). Overall RCLASI modified score was derived by summing the activity and dyspigmentation scores. Overall change from Baseline ranged from -9 to 9, 0 (no change), minus (better) and positive (worse). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data was not collected for Group A as no participants were dosed.

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined.

Posted

Mean

Standard Deviation

Scores on a scale

Baseline (Day 1), Day 14 and Day 28

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions; Placebo	Participants who developed photoprovocation lesions following photoprovocation challenge were planned to be topically administered white to off-white aqueous cream of placebo. The treatments were planned to be administered at the same time on different skin sites once daily for 28 days.

Secondary

Maximum Observed Concentration (Cmax) of GSK2646264 in Participants With Cutaneous Lupus Erythematosus (CLE)

Blood samples were collected at designated timepoints and pharmacokinetic (PK) analysis was performed. Cmax was calculated by non-compartmental analysis using WinNonlin. PK Population comprised of all participants in the safety population for whom a PK sample was obtained and analyzed.

PK Population. All participants received both treatment interventions at the same time (on different skin sites), hence data for these participants were combined. Data was not collected for Group A as no participants were dosed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram per milliliter

Day 1 (pre-dose and 5 hours post-dose), Day 2 to Day 13, Day 14 (pre-dose), Day 21 to Day 27, Day 28 (post-dose), Day 29 to Day 42 and Follow-up (up to Day 56)

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.
OG001	Group B-Participants With Natural Lesions	Participants with natural lesions were topically administered white to off-white aqueous cream of GSK2646264 (1% w/w) and placebo. The treatments were administered at the same time on different skin sites once daily for 28 days.

Secondary

Time to Reach Maximum Observed Concentration (Tmax) of GSK2646264 in Participants With CLE

Blood samples were collected at designated timepoints and PK analysis was performed. Tmax was calculated by non-compartmental analysis using WinNonlin.

Posted

Median

Full Range

Hours

Day 1 (pre-dose and 5 hours post-dose), Day 2 to Day 13, Day 14 (pre-dose), Day 21 to Day 27, Day 28 (post-dose), Day 29 to Day 42 and Follow-up (up to Day 56)

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.
OG001	Group B-Participants With Natural Lesions	Participants with natural lesions were topically administered white to off-white aqueous cream of GSK2646264 (1% w/w) and placebo. The treatments were administered at the same time on different skin sites once daily for 28 days.

Secondary

Mean Fold Change in Messenger Ribonucleic Acid (mRNA) Expression of Interferon (IFN) Signatures in Skin Biopsies

Microarray mRNA data was collected from the skin biopsy in both GSK2646264 and placebo treated lesions on Day -5 to -3 visit (Baseline) and Day 28. Fold change represents the change at Day 28 relative to Baseline for each treatment group. Analysis was conducted using mixed model with participant as a random effect and treatment as a fixed effect where treatment is set to "not applicable" at Baseline. Mean fold change and 95% confidence interval is presented for different genes and probesets. IFI16 indicated interferon, gamma-inducible protein 16, IFI44 indicated interferon-induced protein 44, IFIH1 indicated interferon induced with helicase C domain 1, IFIT1 and 3 indicated interferon-induced protein with tetratricopeptide repeats 1 and 3, MX1 indicated myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse), MX2 indicated myxovirus (influenza virus) resistance 2 (mouse) and OAS indicated 2'-5'-oligoadenylate synthetase.

Safety Population. Only those participants with data available at the specified data points were analyzed. Data was not collected for Group A as no participants were dosed.

Posted

Mean

95% Confidence Interval

Fold change

Baseline (Day -5 to -3) and Day 28

ID	Title	Description
OG000	Group A-Participants With Photoprovocation Lesions; Placebo	Participants who developed photoprovocation lesions following photoprovocation challenge were planned to be topically administered white to off-white aqueous cream of placebo. The treatments were planned to be administered at the same time on different skin sites once daily for 28 days.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0013 events3 affected11 at risk
Tinea pedis	Infections and infestations	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0011 events1 affected11 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0011 events1 affected11 at risk
Postoperative wound complication	Injury, poisoning and procedural complications	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0011 events1 affected11 at risk
Headache	Nervous system disorders	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0011 events1 affected11 at risk
Migraine	Nervous system disorders	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0011 events1 affected11 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0011 events1 affected11 at risk
Panniculitis	Skin and subcutaneous tissue disorders	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0011 events1 affected11 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0012 events1 affected11 at risk
Constipation	Gastrointestinal disorders	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0011 events1 affected11 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0011 events1 affected11 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0011 events1 affected11 at risk
Hot flush	Vascular disorders	MedDRA21.0	Systematic Assessment	EG0000 events0 affected0 at risk EG0011 events1 affected11 at risk

ID	Term
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D012871	Skin Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group A-Participants With Photoprovocation Lesions	Participants who developed lesions following 3 consecutive days of photoprovocation were planned to be administered topical white to off-white GSK2646264 (1 percent [%] weight by weight [w/w]) to 1 lesion and placebo to 1 lesion (at the same time), once daily for 28 consecutive days. Either 1% w/w GSK2646264 or placebo was planned also to be administered to an area of uninvolved skin for 28 days.	0	0	0	0	0	0
EG001	Group B-Participants With Natural Lesions	Participants with natural lesions were topically administered white to off-white aqueous cream of GSK2646264 (1% w/w) and placebo. The treatments were administered at the same time on different skin sites once daily for 28 days.	0	11	1	11	8	11