A Phase 1 interventional study of GSK2646264 1% and Placebo in Lupus Erythematosus, Cutaneous, sponsored by GlaxoSmithKline. Completed at 5 sites in Germany. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2021-04-08.
Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment
This study is designed to examine safety, tolerability, pharmacokinetics, pharmacodynamics and clinical effect of repeat dosing of GSK2646264 in patients with subacute and chronic cutaneous lupus erythematosus (CLE) lesions and in acute CLE like lesions induced by photoprovocation (PV).
Current study is two group study. In Group A, Patients with fewer than two active lesions will be enrolled and exposed to photoprovocation (PV) for 3 consecutive days. Patients that develop PV lesions at any time during this period, as determined by the local investigative team, will receive 1% strength GSK2646264 on 1 lesion and placebo on 1 lesion daily and either 1% strength GSK2646264 or placebo on an area of uninvolved skin, for skin pharmacokinetic (PK) of study drug, for 28 days.
In Group B, Patients that have a minimum of 2 active existing CLE lesions as determined by the investigators will be enrolled into group B and have one lesion treated with 1% GSK2646264 and 1 lesion with placebo.
A completed patient will be defined as a subject who receives at least 25 days of study drug and completes the end of treatment biopsy (at day 28) and assessment. Thereafter patients will be followed for 28 days in Group A only or until complete resolution of induced PV lesions, as determined by the investigator.
1,202 studies on the registry are indexed under Lupus Erythematosus, Systemic; 399 are open to participants now.
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Browse Lupus Erythematosus, Systemic studies →GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.
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Females: Non-reproductive potential defined as:
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.
Patient stable on either no treatment or on :
Exclusion Criteria
The following medications and therapies are prohibited at any time during the study:
Alcohol will be allowed but limited to an average weekly intake of \<21 units for males or \<14 units for females).
Country Specific Exclusion criteria wording for Germany:
Oral Prednisolone
Hydroxychloroquine
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
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
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
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 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
In group B, two chosen lesions will be labeled F and G based on size (F \>G). Subjects will be receiving GSK2646264 1% for lesion F and Placebo for lesion G once daily for 28 days according to randomisation. Skin area H- uninvolved skin will not be assigned any treatment and will be used for the baseline biopsy.
Drug: GSK2646264 1% · Drug: Placebo
In group B, two chosen skin lesions will be labeled F and G based on size (F \>G). Subjects will be receiving Placebo for lesion F and GSK2646264 1% for lesion G once daily for 28 days according to randomisation. Skin area H- uninvolved skin will not be assigned any treatment and will be used for the baseline biopsy.
Drug: GSK2646264 1% · Drug: Placebo
A cream for topical application with a concentration of 1% GSK2646264.
Subjects will receive matching Placebo topically.
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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline (Day 1), Day 14, Day 28 and follow-up (up to Day 56)
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.
Time frame: Baseline (Day 1), Day 14, Day 28 and follow-up (up to Day 56)
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.
Time frame: Day 14 and Day 28
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.
Time frame: Baseline (Day 1), Day 14 and follow-up (up to Day 56)
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.
Time frame: Baseline (Day 1), Day 14 and follow-up (up to Day 56)
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.
Time frame: Up to Day 56
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.
Time frame: Baseline (Day 1), Day 14 and Day 28
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.
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: Baseline (Day -5 to -3) and Day 28
This was a double blind (sponsor unblinded) Phase Ib two group \[group A-photoprovocation (PV) lesions and group B-natural lesions\] study to investigate repeat doses of GSK2646264 administered via topical delivery, on safety, pharmacodynamic effect and clinical efficacy in cutaneous lupus participants.
| Milestone | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| Started | 0 | 11 |
| Completed | 0 | 11 |
| Not completed | 0 | 0 |
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.
| Participants | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| Albumin, Day 14, To low, n=0,11 | — | 0 |
| Albumin, Day 14, To normal or no change, n=0,11 | — | 11 |
| Albumin, Day 28, To low, n=0,10 | — | 0 |
| Albumin, Day 28, To normal or no change, n=0,10 | — | 10 |
| Albumin, Follow-up, To low, n=0,11 | — | 0 |
| Albumin, Follow-up, To normal or no change, n=0,11 | — | 11 |
| ALP, Day 14, To normal or no change, n=0,11 | — | 11 |
| ALP, Day 14, To high, n=0,11 | — | 0 |
| ALP, Day 28, To normal or no change, n=0,10 | — | 10 |
| ALP, Day 28, To high, n=0,10 | — | 0 |
| ALP, Follow-up, To normal or no change, n=0,11 | — | 11 |
| ALP, Follow-up, To high, n=0,11 | — | 0 |
| ALT, Day 14, To normal or no change, n=0,11 | — | 11 |
| ALT, Day 14, To high, n=0,11 | — | 0 |
| ALT, Day 28, To normal or no change, n=0,10 | — | 10 |
| ALT, Day 28, To high, n=0,10 | — | 0 |
| ALT, Follow-up, To normal or no change, n=0,11 | — | 11 |
| ALT, Follow-up, To high, n=0,11 | — | 0 |
| AST, Day 14, To normal or no change, n=0,11 | — | 11 |
| AST, Day 14, To high, n=0,11 | — | 0 |
| AST, Day 28, To normal or no change, n=0,10 | — | 10 |
| AST, Day 28, To high, n=0,10 | — | 0 |
| AST, Follow-up, To normal or no change, n=0,11 | — | 11 |
| AST, Follow-up, To high, n=0,11 | — | 0 |
| TB, Day 14, To normal or no change, n=0,11 | — | 11 |
| TB, Day 14, To high, n=0,11 | — | 0 |
| TB, Day 28, To normal or no change, n=0,10 | — | 10 |
| TB, Day 28, To high, n=0,10 | — | 0 |
| TB, Follow-up, To normal or no change, n=0,11 | — | 11 |
| TB, Follow-up, To high, n=0,11 | — | 0 |
| Calcium, Day 14, To low, n=0,11 | — | 0 |
| Calcium, Day 14, To normal or no change, n=0,11 | — | 11 |
| Calcium, Day 14, To high, n=0,11 | — | 0 |
| Calcium, Day 28, To low, n=0,10 | — | 0 |
| Calcium, Day 28, To normal or no change, n=0,10 | — | 10 |
| Calcium, Day 28, To high, n=0,10 | — | 0 |
| Calcium, Follow-up, To low, n=0,11 | — | 0 |
| Calcium, Follow-up, To normal or no change, n=0,11 | — | 11 |
| Calcium, Follow-up, To high, n=0,11 | — | 0 |
| Glucose, Day 14, To low, n=0,11 | — | 0 |
| Glucose, Day 14, To normal or no change, n=0,11 | — | 11 |
| Glucose, Day 14, To high, n=0,11 | — | 0 |
| Glucose, Day 28, To low, n=0,10 | — | 0 |
| Glucose, Day 28, To normal or no change, n=0,10 | — | 10 |
| Glucose, Day 28, To high, n=0,10 | — | 0 |
| Glucose, Follow-up, To low, n=0,11 | — | 0 |
| Glucose, Follow-up, To normal or no change, n=0,11 | — | 11 |
| Glucose, Follow-up, To high, n=0,11 | — | 0 |
| Pot, Day 14, To low, n=0,11 | — | 0 |
| Pot, Day 14, To normal or no change, n=0,11 | — | 11 |
| Pot, Day 14, To high, n=0,11 | — | 0 |
| Pot, Day 28, To low, n=0,10 | — | 0 |
| Pot, Day 28, To normal or no change, n=0,10 | — | 10 |
| Pot, Day 28, To high, n=0,10 | — | 0 |
| Pot, Follow-up, To low, n=0,11 | — | 0 |
| Pot, Follow-up, To normal or no change, n=0,11 | — | 11 |
| Pot, Follow-up, To high, n=0,11 | — | 0 |
| Sodium, Day 14, To low, n=0,11 | — | 0 |
| Sodium, Day 14, To normal or no change, n=0,11 | — | 11 |
| Sodium, Day 14, To high, n=0,11 | — | 0 |
| Sodium, Day 28, To low, n=0,10 | — | 0 |
| Sodium, Day 28, To normal or no change, n=0,10 | — | 10 |
| Sodium, Day 28, To high, n=0,10 | — | 0 |
| Sodium, Follow-up, To low, n=0,11 | — | 0 |
| Sodium, Follow-up, To normal or no change, n=0,11 | — | 11 |
| Sodium, Follow-up, To high, n=0,11 | — | 0 |
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.
| Participants | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| Baso, Day 14, To normal or no change, n=0,10 | — | 10 |
| Baso, Day 14, To high, n=0,10 | — | 0 |
| Baso, Day 28, To normal or no change, n=0,10 | — | 10 |
| Baso, Day 28, To high, n=0,10 | — | 0 |
| Baso, Follow-up, To normal or no change, n=0,11 | — | 11 |
| Baso, Follow-up, To high, n=0,11 | — | 0 |
| Eos, Day 14, To normal or no change, n=0,10 | — | 10 |
| Eos, Day 14, To high, n=0,10 | — | 0 |
| Eos, Day 28, To normal or no change, n=0,10 | — | 10 |
| Eos, Day 28, To high, n=0,10 | — | 0 |
| Eos, Follow-up, To normal or no change, n=0,11 | — | 11 |
| Eos, Follow-up, To high n=0,11 | — | 0 |
| Hb, Day 14, To normal or no change, n=0,10 | — | 10 |
| Hb, Day 14, To high, n=0,10 | — | 0 |
| Hb, Day 28, To normal or no change, n=0,10 | — | 10 |
| Hb, Day 28, To high, n=0,10 | — | 0 |
| Hb, Follow-up, To normal or no change, n=0,11 | — | 11 |
| Hb, Follow-up, To high, n=0,11 | — | 0 |
| Hct, Day 14, To normal or no change, n=0,10 | — | 10 |
| Hct, Day 14, To high, n=0,10 | — | 0 |
| Hct, Day 28, To normal or no change, n=0,10 | — | 10 |
| Hct, Day 28, To high, n=0,10 | — | 0 |
| Hct, Follow-up, To normal or no change, n=0,11 | — | 11 |
| Hct, Follow-up, To high, n=0,11 | — | 0 |
| Lympho, Day 14, To low, n=0,10 | — | 0 |
| Lympho, Day 14, To normal or no change, n=0,10 | — | 10 |
| Lympho, Day 28, To low, n=0,10 | — | 0 |
| Lympho, Day 28, To normal or no change, n=0,10 | — | 10 |
| Lympho, Follow-up, To low, n=0,11 | — | 0 |
| Lympho, Follow-up, To normal or no change, n=0,11 | — | 11 |
| Mono, Day 14, To low, n=0,10 | — | 0 |
| Mono, Day 14, To normal or no change, n=0,10 | — | 10 |
| Mono, Day 14, To high, n=0,10 | — | 0 |
| Mono, Day 28, To low, n=0,10 | — | 1 |
| Mono, Day 28, To normal or no change, n=0,10 | — | 9 |
| Mono, Day 28, To high, n=0,10 | — | 0 |
| Mono, Follow-up, To low, n=0,11 | — | 0 |
| Mono, Follow-up, To normal or no change, n=0,11 | — | 11 |
| Mono, Follow-up, To high, n=0,11 | — | 0 |
| Neutro, Day 14, To low, n=0,10 | — | 1 |
| Neutro, Day 14, To normal or no change, n=0,10 | — | 9 |
| Neutro, Day 28, To low, n=0,10 | — | 0 |
| Neutro, Day 28, To normal or no change, n=0,10 | — | 10 |
| Neutro, Follow-up, To low, n=0,11 | — | 0 |
| Neutro, Follow-up, To normal or no change, n=0,11 | — | 11 |
| PC, Day 14, To low, n=0,10 | — | 0 |
| PC, Day 14, To normal or no change, n=0,10 | — | 10 |
| PC, Day 14, To high, n=0,10 | — | 0 |
| PC, Day 28, To low, n=0,10 | — | 0 |
| PC, Day 28, To normal or no change, n=0,10 | — | 10 |
| PC, Day 28, To high, n=0,10 | — | 0 |
| PC, Follow-up, To low, n=0,11 | — | 0 |
| PC, Follow-up, To normal or no change, n=0,11 | — | 11 |
| PC, Follow-up, To high, n=0,11 | — | 0 |
| RBC, Day 14, To low, n=0,10 | — | 0 |
| RBC, Day 14, To normal or no change, n=0,10 | — | 10 |
| RBC, Day 14, To high, n=0,10 | — | 0 |
| RBC, Day 28, To low, n=0,10 | — | 1 |
| RBC, Day 28, To normal or no change, n=0,10 | — | 9 |
| RBC, Day 28, To high, n=0,10 | — | 0 |
| RBC, Follow-up, To low, n=0,11 | — | 0 |
| RBC, Follow-up, To normal or no change, n=0,11 | — | 11 |
| RBC, Follow-up, To high, n=0,11 | — | 0 |
| WBC, Day 14, To low, n=0,10 | — | 0 |
| WBC, Day 14, To normal or no change, n=0,10 | — | 10 |
| WBC, Day 14, To high, n=0,10 | — | 0 |
| WBC, Day 28, To low, n=0,10 | — | 0 |
| WBC, Day 28, To normal or no change, n=0,10 | — | 10 |
| WBC, Day 28, To high, n=0,10 | — | 0 |
| WBC, Follow-up, To low, n=0,11 | — | 0 |
| WBC, Follow-up, To normal or no change, n=0,11 | — | 11 |
| WBC, Follow-up, To high, n=0,11 | — | 0 |
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.
| pH | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| Day 14, n=0,10 | — | -0.10 ± 0.843 |
| Day 28, n=0,10 | — | -0.35 ± 0.669 |
| Follow-up, n=0,11 | — | -0.32 ± 0.783 |
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.
| kilogram per meter cube | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| Day 14, n=0,10 | — | 0.0007 ± 0.00629 |
| Day 28, n=0,10 | — | -0.0001 ± 0.00626 |
| Follow-up, n=0,11 | — | 0.0003 ± 0.00746 |
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.
| Participants | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| DBP, Day 14, To low, n=0,10 | — | 0 |
| DBP, Day 14, To normal or no change, n=0,10 | — | 10 |
| DBP, Day 14, To high, n=0,10 | — | 0 |
| DBP, Day 28, To low, n=0,11 | — | 0 |
| DBP, Day 28, To normal or no change, n=0,11 | — | 11 |
| DBP, Day 28, To high, n=0,11 | — | 0 |
| HR, Day 14, To low, n=0,10 | — | 0 |
| HR, Day 14, To normal or no change, n=0,10 | — | 10 |
| HR, Day 14, To high, n=0,10 | — | 0 |
| HR, Day 28, To low, n=0,11 | — | 0 |
| HR, Day 28, To normal or no change, n=0,11 | — | 11 |
| HR, Day 28, To high, n=0,11 | — | 0 |
| SBP, Day 14, To low, n=0,10 | — | 0 |
| SBP, Day 14, To normal or no change, n=0,10 | — | 10 |
| SBP, Day 14, To high, n=0,10 | — | 0 |
| SBP, Day 28, To low, n=0,11 | — | 0 |
| SBP, Day 28, To normal or no change, n=0,11 | — | 11 |
| SBP, Day 28, To high, n=0,11 | — | 0 |
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.
| bpm | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| HR, Day 14, n=0,10 | — | 1.633 ± 8.3702 |
| HR, Follow-up, n=0,11 | — | -0.606 ± 4.1280 |
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.
| Milliseconds | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| PR interval, Day 14, n=0,10 | — | -0.900 ± 5.2306 |
| PR interval, Follow-up, n=0,11 | — | 3.424 ± 11.4174 |
| QRS duration, Day 14, n=0,10 | — | -0.967 ± 3.4728 |
| QRS duration, Follow-up, n=0,11 | — | 1.061 ± 3.5113 |
| QT interval, Day 14, n=0,10 | — | -4.467 ± 21.8955 |
| QT interval, Follow-up, n=0,11 | — | 4.455 ± 17.5463 |
| QTcF interval, Day 14, n=0,3 | — | -2.739 ± 7.4559 |
| QTcF interval, Follow-up, n=0,4 | — | 4.532 ± 10.0979 |
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.
| Participants | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| Any AEs | — | 8 |
| Any SAEs | — | 1 |
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.
| Scores on a scale | Group A-Participants With Photoprovocation Lesions; Placebo | Group A-Participants With Photoprovocation Lesions; GSK2646264 | Group B-Participants With Natural Lesions; Placebo | Group B-Participants With Natural Lesions; GSK2646264 |
|---|---|---|---|---|
| Erythema, Day 14, n=0,0,9,9 | — | — | -0.8 ± 0.83 | -0.8 ± 0.83 |
| Erythema, Day 28, n=0,0,10,10 | — | — | -0.5 ± 0.71 | -0.5 ± 0.71 |
| Scaling/Hyperkeratosis, Day 14, n=0,0,9,9 | — | — | 0.0 ± 0.00 | 0.0 ± 0.00 |
| Scaling/Hyperkeratosis, Day 28, n=0,0,10,10 | — | — | 0.0 ± 0.00 | 0.0 ± 0.00 |
| Edema/infiltration, Day 14, n=0,0,9,9 | — | — | -0.2 ± 0.44 | -0.2 ± 0.44 |
| Edema/infiltration, Day 28, n=0,0,10,10 | — | — | -0.4 ± 0.52 | -0.3 ± 0.48 |
| Dyspigmentation, Day 14, n=0,0,9,9 | — | — | -0.1 ± 0.33 | -0.1 ± 0.33 |
| Dyspigmentation, Day 28, n=0,0,10,10 | — | — | -0.1 ± 0.32 | -0.1 ± 0.32 |
| Modified RCLASI, Day 14, n=0,0,9,9 | — | — | -1.0 ± 1.22 | -1.0 ± 1.12 |
| Modified RCLASI, Day 28, n=0,0,10,10 | — | — | -0.9 ± 1.20 | -0.8 ± 1.14 |
| Overall RCLASI modified, Day 14, n=0,0,9,9 | — | — | -1.1 ± 1.45 | -1.1 ± 1.36 |
| Overall RCLASI modified, Day 28, n=0,0,10,10 | — | — | -1.0 ± 1.33 | -0.9 ± 1.37 |
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.
| Nanogram per milliliter | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| Maximum Observed Concentration (Cmax) of GSK2646264 in Participants With Cutaneous Lupus Erythematosus (CLE) | — | 0.8324 ± 109.3 |
Blood samples were collected at designated timepoints and PK analysis was performed. Tmax was calculated by non-compartmental analysis using WinNonlin.
| Hours | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| Time to Reach Maximum Observed Concentration (Tmax) of GSK2646264 in Participants With CLE | — | 311.467 (4.68 to 651.92) |
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.
| Fold change | Group A-Participants With Photoprovocation Lesions; Placebo | Group A-Participants With Photoprovocation Lesions; GSK2646264 | Group B-Participants With Natural Lesions; Placebo | Group B-Participants With Natural Lesions; GSK2646264 |
|---|---|---|---|---|
| Chemokine (C-X-C motif)Ligand10, 204533_at, Day 28 | — | — | 1.173 (-1.899 to 2.610) | -1.464 (-3.259 to 1.521) |
| IFI16, 206332_s_at, Day 28 | — | — | -1.001 (-1.286 to 1.283) | -1.064 (-1.367 to 1.207) |
| IFI16, 208965_s_at, Day 28 | — | — | 1.055 (-1.219 to 1.356) | -1.164 (-1.496 to 1.105) |
| IFI16, 208966_x_at, Day 28 | — | — | -1.044 (-1.328 to 1.219) | -1.096 (-1.394 to 1.161) |
| IFI44, 214059_at, Day 28 | — | — | 1.018 (-1.429 to 1.481) | -1.029 (-1.497 to 1.413) |
| IFI44, 214453_s_at, Day 28 | — | — | 1.021 (-1.541 to 1.606) | -1.270 (-1.998 to 1.239) |
| IFI44-like, 204439_at, Day 28 | — | — | 1.043 (-1.602 to 1.744) | -1.122 (-1.875 to 1.491) |
| IFIH1, 1555464_at, Day 28 | — | — | 1.037 (-1.081 to 1.162) | -1.074 (-1.204 to 1.043) |
| IFIH1, 216020_at, Day 28 | — | — | 1.035 (-1.062 to 1.138) | -1.044 (-1.148 to 1.053) |
| IFIH1, 219209_at, Day 28 | — | — | -1.025 (-1.577 to 1.500) | -1.295 (-1.991 to 1.188) |
| IFIT1, 203153_at, Day 28 | — | — | 1.011 (-1.664 to 1.701) | -1.113 (-1.872 to 1.512) |
| IFIT3, 204747_at, Day 28 | — | — | 1.039 (-1.643 to 1.772) | -1.221 (-2.084 to 1.397) |
| IFIT3, 229450_at, Day 28 | — | — | 1.096 (-1.457 to 1.749) | -1.138 (-1.817 to 1.402) |
| Interleukin 1, alpha, 208200_at, Day 28 | — | — | 1.016 (-1.324 to 1.367) | -1.217 (-1.638 to 1.105) |
| Interleukin 1, alpha, 210118_s_at, Day 28 | — | — | -1.015 (-1.117 to 1.085) | -1.169 (-1.287 to -1.062) |
| Interleukin 1, beta, 205067_at, Day 28 | — | — | 1.081 (-1.145 to 1.337) | -1.131 (-1.399 to 1.094) |
| Interleukin 1, beta, 39402_at, Day 28 | — | — | 1.087 (-1.166 to 1.377) | -1.094 (-1.386 to 1.158) |
| Interleukin 6, 205207_at, Day 28 | — | — | 1.014 (-1.077 to 1.107) | 1.063 (-1.027 to 1.161) |
| ISG15 ubiquitin-like modifier, 205483_s_at, Day 28 | — | — | -1.086 (-2.044 to 1.732) | -1.343 (-2.527 to 1.401) |
| MX1, 202086_at, Day 28 | — | — | 1.059 (-1.244 to 1.395) | -1.028 (-1.354 to 1.281) |
| MX2, 204994_at, Day 28 | — | — | 1.122 (-1.271 to 1.601) | -1.039 (-1.482 to 1.374) |
| OAS1, 40/46 kilodalton, 202869_at, Day 28 | — | — | 1.092 (-1.219 to 1.453) | -1.168 (-1.555 to 1.139) |
| OAS1, 40/46 kilodalton, 205552_s_at, Day 28 | — | — | 1.088 (-1.391 to 1.646) | -1.296 (-1.961 to 1.168) |
| OAS2, 69/71 kilodalton, 204972_at, Day 28 | — | — | 1.165 (-1.347 to 1.826) | -1.157 (-1.814 to 1.355) |
| OAS2, 69/71 kilodalton, 206553_at, Day 28 | — | — | 1.061 (-1.186 to 1.334) | -1.010 (-1.270 to 1.246) |
| OAS2, 69/71 kilodalton, 228607_at, Day 28 | — | — | 1.065 (-1.478 to 1.676) | 1.000 (-1.574 to 1.574) |
| OAS3, 100 kilodalton, 218400_at, Day 28 | — | — | 1.141 (-1.370 to 1.784) | -1.089 (-1.702 to 1.436) |
| OAS3, 100 kilodalton, 232666_at, Day 28 | — | — | 1.096 (-1.274 to 1.529) | 1.109 (-1.259 to 1.548) |
| OAS-like, 205660_at, Day 28 | — | — | 1.179 (-1.586 to 2.206) | -1.217 (-2.276 to 1.537) |
| OAS-like, 210797_s_at, Day 28 | — | — | 1.178 (-1.508 to 2.091) | -1.112 (-1.973 to 1.597) |
Collected over Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment up to Day 56. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group A-Participants With Photoprovocation Lesions | — | — | — |
| Group B-Participants With Natural Lesions | 0/11 (0%) | 1/11 (9.1%) | 8/11 (72.7%) |
| Event | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| Ankle fractureInjury, poisoning and procedural complications | — | 1/11 |
| Event | Group A-Participants With Photoprovocation Lesions | Group B-Participants With Natural Lesions |
|---|---|---|
| NasopharyngitisInfections and infestations | — | 3/11 |
| Tinea pedisInfections and infestations | — | 1/11 |
| Post procedural haemorrhageInjury, poisoning and procedural complications | — | 1/11 |
| Postoperative wound complicationInjury, poisoning and procedural complications | — | 1/11 |
| HeadacheNervous system disorders | — | 1/11 |
| MigraineNervous system disorders | — | 1/11 |
| Dermatitis contactSkin and subcutaneous tissue disorders | — | 1/11 |
| PanniculitisSkin and subcutaneous tissue disorders | — | 1/11 |
| PruritusSkin and subcutaneous tissue disorders | — | 1/11 |
| ConstipationGastrointestinal disorders | — | 1/11 |
All participants received both treatment interventions at the same time (on different skin sites), hence, data for these participants were combined.
| Age, Continuous(Years) | Group A-Participants With Photoprovocation Lesions | Group B- Participants With Natural Lesions | Total |
|---|---|---|---|
| Mean | — | 54.8 ± 10.44 | 54.8 ± 10.44 |
| Sex: Female, Male(Participants) | Group A-Participants With Photoprovocation Lesions | Group B- Participants With Natural Lesions | Total |
|---|---|---|---|
| Female | 0 | 9 | 9 |
| Male | 0 | 2 | 2 |
| Race/Ethnicity, Customized(Participants) | Group A-Participants With Photoprovocation Lesions | Group B- Participants With Natural Lesions | Total |
|---|---|---|---|
| Race — Black or African American | 0 | 1 | 1 |
| Race — White/Caucasian/European heritage | 0 | 10 | 10 |
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Plan to share: Yes — IPD for this study is available via the Clinical Study Data Request site.
Supporting information: Study protocol, Sap, Icf, Csr
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Lupus Erythematosus, Systemic→
GlaxoSmithKline