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This is the first study with GSK2982772, a receptor-interacting protein-1 (RIP1) kinase inhibitor, in subjects with active plaque-type psoriasis (PsO). The primary objective will be to investigate the safety and tolerability of repeat oral doses of GSK2982772 60 milligram (mg) twice daily (BID) for 84 days in Cohort 1 and 60 mg thrice daily (TID) for 84 days in Cohort 2. In addition, a number of experimental and clinical endpoints will be employed to obtain information on the pharmacokinetics, pharmacodynamics, and efficacy in subjects with active PsO. There will be two Cohorts of subjects. In Cohort 1 after a screening period of up to 30 days, approximately 30 subjects will be randomized to receive either GSK2982772 60 mg BID or placebo for 84 days (12 Weeks), followed by a follow-up period (28 days). In Cohort 2 after a screening period of up to 30 days, approximately 24 subjects will be randomized to receive either GSK2982772 60 mg TID or placebo for 84 days (12 Weeks), followed by a follow-up period (28 days). The total duration of participation is approximately 20 Weeks from screening to the last study visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK2982772 receivers in Cohort 1 | Experimental | Randomized subjects will receive GSK2982772 BID (approximately 12 hours apart) via oral route for 84 days. |
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| Placebo receivers in Cohort 1 | Placebo Comparator | Randomized subjects will receive placebo BID via oral route for 84 days. |
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| GSK2982772 receivers in Cohort 2 | Experimental | Randomized subjects will receive GSK2982772 TID (approximately 8 hours apart) via oral route for 84 days |
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| Placebo receivers in Cohort 2 | Placebo Comparator | Randomized subjects will receive placebo TID via oral route for 84 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2982772 | Drug | GSK2982772 will be supplied as a white to almost white, round, film coated 30 mg oral tablets; two tablets to be taken in the morning and two in the evening, as directed for Cohort 1 and for Cohort 2 two tablets to be taken three times daily as directed. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | An AE is any untoward medical occurrence in a participant or clinical investigation 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 hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least one dose of study treatment. | Up to Day 116 |
| Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria | Blood samples were collected for analysis of clinical chemistry parameters. Clinical concern ranges were >=2x Upper Limit of Normal (ULN) units per liter (U/L) for alanine aminotransferase (ALT), <30 millimoles per liter (mmol/L) for albumin, >=2x ULN U/L for alkaline phosphatase, >=2x ULN U/L for aspartate aminotransferase (AST), <2 or >2.75 mmol/L for Calcium, >44.2 mmol/L for Creatinine, <3 or >9 mmol/L for Glucose, <3 or>5.5 mmol/L for Potassium, <130 or >150 mmol/L for Sodium, and >=1.5xULN micromoles per liter for total bilirubin. Participants were counted in worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (example given [e.g.], High to High), or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High', Baseline is defined as the latest pre-dose assessment. | Up to Day 116 |
| Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria | Blood samples were collected for analysis of hematology parameters. Clinical concern ranges were >0.54 calculated as proportion of red blood cells in blood for Hematocrit, >180 grams per liter for Hemoglobin, <0.8 x10^9 cells per liter for Lymphocytes, <1.5 x10^9 cells per liter for Neutrophil count, <100 or >550 x10^9 cells per liter for Platelet count and <3 or >20 x10^9 cells per liter White Blood Cell count. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Concentrations of GSK2982772 at Days 43 and 85 | Blood samples were collected for pharmacokinetic analysis of GSK2982772 following 60 mg BID and 60 mg TID dose at indicated time points. The pharmacokinetic analysis was performed using non-compartmental methods. The analysis was based on Pharmacokinetic Population which comprised of participants in the 'Safety' Population for whom a pharmacokinetic sample was obtained and analyzed. |
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Inclusion Criteria:
Both must be of a suitable size (>=3 centimeter [cm] by 3 cm) and one in a site suitable for repeat biopsy, and one in a site suitable for index lesion PLSS scoring.
Both plaques must have a PLSS lesional score >=2 for the induration component (moderate or above), >=1 for erythema and scaling with a total score of >=5.
The biopsy lesion must not be on the face, groin, scalp, knees, elbows, or on the palmar/plantar surfaces of the hands/feet, and must be shielded from natural light with clothing.
Males: Male subjects with female partners of child bearing potential must comply with the pre specified contraception requirements.
Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotropin test), not lactating, and is either of non-reproductive potential or reproductive potential. If of reproductive potential, then the subject should agree to follow one of the options listed per GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential from 30 days prior to the first dose and until 30 days after the last dose of study medication The Investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
Exclusion Criteria:
Hospitalization for treatment of infection within 60 days before first dose (Day 1).
Currently on any suppressive therapy for a chronic infection (such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria).
Use of parenteral (intravenous or intramuscular) antibiotics (antibacterials, antivirals, antifungals, or antiparasitic agents) within 60 days before first dose.
A history of opportunistic infections within 1 year of screening (e.g. pneumocystis jirovecii, cytomegalovirus, pneumonitis, aspergillosis). This does not include infections that may occur in immunocompetent individuals, such as fungal nail infections or vaginal candidiasis, unless it is of an unusual severity or recurrent nature.
Recurrent or chronic infection or other active infection that, in the opinion of the Investigator might cause this study to be detrimental to the subject.
History of tuberculosis (TB), irrespective of treatment status. A positive diagnostic TB test at screening defined as a positive QuantiFERON-TB Gold test or T-spot test.
In cases where the QuantiFERON or T-spot test is indeterminate, the subject may have the test repeated once, but they will not be eligible for the study unless the second test is negative.
In cases where the QuantiFERON or T-spot test is positive, but a locally-read follow up chest X-ray, shows no evidence of current or previous pulmonary tuberculosis, the subject may be eligible for the study at the discretion of the Investigator and medical monitor.
Other medications (including vitamins, herbal and dietary supplements) will be considered on a case-by-case basis, and will be allowed if in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject safety.
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Markham | Ontario | L3P1X2 | Canada | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32301501 | Background | Weisel K, Berger S, Papp K, Maari C, Krueger JG, Scott N, Tompson D, Wang S, Simeoni M, Bertin J, Peter Tak P. Response to Inhibition of Receptor-Interacting Protein Kinase 1 (RIPK1) in Active Plaque Psoriasis: A Randomized Placebo-Controlled Study. Clin Pharmacol Ther. 2020 Oct;108(4):808-816. doi: 10.1002/cpt.1852. Epub 2020 Jul 7. |
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IPD for this study will be made available via the Clinical Study Data Request site.
IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
A total of 100 participants were screened, of which, 65 participants were enrolled in the study.
This was a repeat dose study in participants with active plaque-type psoriasis. Participants received either GSK2982772 60 milligrams (mg) or placebo orally twice daily (BID) in Cohort 1 and either GSK2982772 60 mg or placebo orally three times daily (TID) in Cohort 2. The study was conducted at 4 centers in Canada.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study. |
| FG001 | GSK2982772 60 mg BID | Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study. |
| FG002 | GSK2982772 60 mg TID | Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study. |
| BG001 | GSK2982772 60 mg BID | Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 Serious Adverse Events (SAEs) and Non-SAEs | An AE is any untoward medical occurrence in a participant or clinical investigation 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 hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least one dose of study treatment. | Safety Population | Posted | Count of Participants | Participants | Up to Day 116 |
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Serious adverse events (SAEs) and non-SAEs were collected from the start of study treatment until follow-up (up to Day 116)
SAEs and non-SAEs were reported for the Safety Population.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Eligible participants received placebo orally BID, for 12 weeks in Cohort 1 and orally TID for 12 weeks in Cohort 2 of the study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA20.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA20.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 12, 2017 | Oct 15, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 24, 2017 | Oct 15, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D011565 | Psoriasis |
| ID | Term |
|---|---|
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C000708951 | GSK2982772 |
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| Placebo | Drug | Matching placebo will be supplied as a white to almost white, round film coated tablets; two tablets to be taken in the morning and two in the evening, as directed for Cohort 1 and for Cohort 2 two tablets to be taken three times daily as directed. |
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| Up to Day 116 |
| Change From Baseline in Urine Potential of Hydrogen (pH) | Urine samples were collected for measurement of urine pH at indicated time points. pH is a measure of hydrogen ion concentration and used to determine the acidity or alkalinity of urine. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116) |
| Change From Baseline in Urine Specific Gravity | Urine samples were collected to analyze specific gravity of urine. 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. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116) |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Blood pressure was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116) |
| Change From Baseline in Heart Rate | Heart rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116) |
| Change From Baseline in Respiratory Rate | Respiratory rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116) |
| Change From Baseline in Body Temperature | Body temperature was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116) |
| Number of Participants With Any Time Post-Baseline Results for Electrocardiogram Findings | Single 12-lead electrocardiograms were obtained at indicated time points during the study using an electrocardiogram machine that automatically calculates the heart rate and measures PR, QRS, QT, QT interval corrected for heart rate (QTc) using Bazett's formula (QTcB) intervals and QTc using Fridericia's formula (QTcF). The abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Baseline is defined as the latest pre-dose assessment. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. The number of participants with normal and abnormal electrocardiogram findings at any time post-Baseline visit has been presented. | Up to Day 116 |
| Day 43 (Pre-dose) and Day 85 |
| Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43 | Blood samples were collected for pharmacokinetic analysis of GSK2982772 following 60 mg BID and 60 mg TID dose at indicated time points. The pharmacokinetic analysis was performed using non-compartmental methods. | 1, 2, 4 and 6 Hours Post-dose on Days 1 and 43 |
| Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772 | A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of Cluster of differentiation 11 (CD11+), CD161+, CD3+ and Elastase. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Data for all the listed biomarkers from skin biopsy has been presented for two skin types; dermis and epidermis at Day 43. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses. NA indicates that data was not available as geometric coefficient of variation could not be calculated for single participant. | Baseline (Pre-dose on Day 1) and Day 43 |
| Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy: Epidermis Thickness | A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of epidermis thickness. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses. | Baseline (Pre-dose on Day 1) and Day 43 |
| Number of Participants With Changes in Keratin 16 (K16) Histopathological Scoring in Psoriatic Lesional Biopsies | A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of K16 as keratin expression. Baseline is defined as the latest pre-dose assessment. Results for K16 were categorized as, negative to positive, no change and positive to negative at Day 43. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses. | Baseline (Pre-dose on Day 1) and Day 43 |
| Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772 | A target lesion for biopsy was identified on the trunk or extremities at indicated time points. mRNA expression of inflammatory markers and tissue healing were assessed. Data has been presented for inflammatory gene transcripts including interferon gamma, interleukin 10, interleukin 17A, interleukin 21, interleukin 22, interleukin 23 subunit alpha, interleukin 4 and tumor necrosis factor. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses. | Day 1 and Day 43 |
| Percentage Change From Baseline Psoriatic Lesion Severity Sum (PLSS) Scores in the Index Lesion Following Administration of GSK2982772 | Two plaques were selected, one for clinical assessment (index plaque) and one for biopsy. Each lesion was evaluated for 3 components: erythema, induration, and scaling. Each component was given a score using a scale ranging from 0 (no symptom) to 4 (very marked) with increasing score reflecting increased lesion severity. The PLSS is the sum of the erythema, scaling and plaque thickness scores. The total PLSS score ranged from 0 (no symptom) to 12 (very marked). Each lesion must have a PLSS score of >=5. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all efficacy analyses. | Baseline (Pre-dose on Day 1) and Days 15, 29, 43, 57, 71, 85 |
| Actual PLSS Scores in the Index Psoriatic Lesion Following Administration of GSK2982772 | Two plaques were selected one for clinical assessment (index plaque) and one for biopsy. Each lesion was evaluated for 3 components: erythema, induration, and scaling. Each component was given a score using a scale ranging from 0 (no symptom) to 4 (very marked) with increasing score reflecting increased lesion severity. The PLSS is the sum of the erythema, scaling and plaque thickness scores. The total PLSS score ranged from 0 (no symptom) to 12 (very marked). Each lesion must have a PLSS score of >=5. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all efficacy analyses. | Days 1, 15, 29, 43, 57, 71 and 85 |
| Peterborough |
| Ontario |
| K9J 5K2 |
| Canada |
| GSK Investigational Site | Waterloo | Ontario | N2J 1C4 | Canada |
| GSK Investigational Site | Montreal | Quebec | H2K 4L5 | Canada |
| Lost to Follow-up |
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| Adverse Event |
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| BG002 | GSK2982772 60 mg TID | Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study. |
| BG003 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| OG001 | GSK2982772 60 mg BID | Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study. |
| OG002 | GSK2982772 60 mg TID | Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study. |
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| Primary | Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria | Blood samples were collected for analysis of clinical chemistry parameters. Clinical concern ranges were >=2x Upper Limit of Normal (ULN) units per liter (U/L) for alanine aminotransferase (ALT), <30 millimoles per liter (mmol/L) for albumin, >=2x ULN U/L for alkaline phosphatase, >=2x ULN U/L for aspartate aminotransferase (AST), <2 or >2.75 mmol/L for Calcium, >44.2 mmol/L for Creatinine, <3 or >9 mmol/L for Glucose, <3 or>5.5 mmol/L for Potassium, <130 or >150 mmol/L for Sodium, and >=1.5xULN micromoles per liter for total bilirubin. Participants were counted in worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (example given [e.g.], High to High), or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High', Baseline is defined as the latest pre-dose assessment. | Safety Population. Only those clinical chemistry parameters with data available per PCI criteria have been presented. | Posted | Count of Participants | Participants | Up to Day 116 |
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| Primary | Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria | Blood samples were collected for analysis of hematology parameters. Clinical concern ranges were >0.54 calculated as proportion of red blood cells in blood for Hematocrit, >180 grams per liter for Hemoglobin, <0.8 x10^9 cells per liter for Lymphocytes, <1.5 x10^9 cells per liter for Neutrophil count, <100 or >550 x10^9 cells per liter for Platelet count and <3 or >20 x10^9 cells per liter White Blood Cell count. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. | Safety Population. Only those hematology parameters with data available per PCI criteria have been presented. | Posted | Count of Participants | Participants | Up to Day 116 |
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| Primary | Change From Baseline in Urine Potential of Hydrogen (pH) | Urine samples were collected for measurement of urine pH at indicated time points. pH is a measure of hydrogen ion concentration and used to determine the acidity or alkalinity of urine. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Potential of hydrogen (pH) | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116) |
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| Primary | Change From Baseline in Urine Specific Gravity | Urine samples were collected to analyze specific gravity of urine. 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. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Ratio | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116) |
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| Primary | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Blood pressure was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Millimeter of mercury | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116) |
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| Primary | Change From Baseline in Heart Rate | Heart rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116) |
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| Primary | Change From Baseline in Respiratory Rate | Respiratory rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Breaths per minute | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116) |
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| Primary | Change From Baseline in Body Temperature | Body temperature was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value. | Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Celsius | Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85 and Follow-up (Day 116) |
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| Primary | Number of Participants With Any Time Post-Baseline Results for Electrocardiogram Findings | Single 12-lead electrocardiograms were obtained at indicated time points during the study using an electrocardiogram machine that automatically calculates the heart rate and measures PR, QRS, QT, QT interval corrected for heart rate (QTc) using Bazett's formula (QTcB) intervals and QTc using Fridericia's formula (QTcF). The abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Baseline is defined as the latest pre-dose assessment. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. The number of participants with normal and abnormal electrocardiogram findings at any time post-Baseline visit has been presented. | Safety Population | Posted | Count of Participants | Participants | Up to Day 116 |
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| Secondary | Plasma Concentrations of GSK2982772 at Days 43 and 85 | Blood samples were collected for pharmacokinetic analysis of GSK2982772 following 60 mg BID and 60 mg TID dose at indicated time points. The pharmacokinetic analysis was performed using non-compartmental methods. The analysis was based on Pharmacokinetic Population which comprised of participants in the 'Safety' Population for whom a pharmacokinetic sample was obtained and analyzed. | Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Nanograms per milliliter | Day 43 (Pre-dose) and Day 85 |
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| Secondary | Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43 | Blood samples were collected for pharmacokinetic analysis of GSK2982772 following 60 mg BID and 60 mg TID dose at indicated time points. The pharmacokinetic analysis was performed using non-compartmental methods. | Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Nanograms per milliliter | 1, 2, 4 and 6 Hours Post-dose on Days 1 and 43 |
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| Secondary | Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy Following Administration of GSK2982772 | A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of Cluster of differentiation 11 (CD11+), CD161+, CD3+ and Elastase. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Data for all the listed biomarkers from skin biopsy has been presented for two skin types; dermis and epidermis at Day 43. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses. NA indicates that data was not available as geometric coefficient of variation could not be calculated for single participant. | Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Percent change | Baseline (Pre-dose on Day 1) and Day 43 |
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| Secondary | Adjusted Mean Percentage Change in Histopathological Scoring of Psoriatic Lesional Biopsy: Epidermis Thickness | A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of epidermis thickness. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses. | Safety Population. Only those participants with data available at specified time point were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percent change | Baseline (Pre-dose on Day 1) and Day 43 |
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| Secondary | Number of Participants With Changes in Keratin 16 (K16) Histopathological Scoring in Psoriatic Lesional Biopsies | A target lesion for biopsy was identified on the trunk or extremities at indicated time points. The manual cell counting performed on stained tissue section was referred as histopathological scoring of psoriatic lesions. Histologic assessment included measurement of K16 as keratin expression. Baseline is defined as the latest pre-dose assessment. Results for K16 were categorized as, negative to positive, no change and positive to negative at Day 43. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses. | Safety Population | Posted | Count of Participants | Participants | Baseline (Pre-dose on Day 1) and Day 43 |
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| Secondary | Messenger Ribonucleic Acid (mRNA) Expression of Inflammatory Gene Transcripts in Psoriatic Lesional Biopsies Following Administration of GSK2982772 | A target lesion for biopsy was identified on the trunk or extremities at indicated time points. mRNA expression of inflammatory markers and tissue healing were assessed. Data has been presented for inflammatory gene transcripts including interferon gamma, interleukin 10, interleukin 17A, interleukin 21, interleukin 22, interleukin 23 subunit alpha, interleukin 4 and tumor necrosis factor. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all biomarker analyses. | Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Copies per 25 nanogram RNA | Day 1 and Day 43 |
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| Secondary | Percentage Change From Baseline Psoriatic Lesion Severity Sum (PLSS) Scores in the Index Lesion Following Administration of GSK2982772 | Two plaques were selected, one for clinical assessment (index plaque) and one for biopsy. Each lesion was evaluated for 3 components: erythema, induration, and scaling. Each component was given a score using a scale ranging from 0 (no symptom) to 4 (very marked) with increasing score reflecting increased lesion severity. The PLSS is the sum of the erythema, scaling and plaque thickness scores. The total PLSS score ranged from 0 (no symptom) to 12 (very marked). Each lesion must have a PLSS score of >=5. Baseline is defined as the latest pre-dose assessment. Percentage change from Baseline was determined from the back-calculation of the log ratio to Baseline. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all efficacy analyses. | Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Percentage change | Baseline (Pre-dose on Day 1) and Days 15, 29, 43, 57, 71, 85 |
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| Secondary | Actual PLSS Scores in the Index Psoriatic Lesion Following Administration of GSK2982772 | Two plaques were selected one for clinical assessment (index plaque) and one for biopsy. Each lesion was evaluated for 3 components: erythema, induration, and scaling. Each component was given a score using a scale ranging from 0 (no symptom) to 4 (very marked) with increasing score reflecting increased lesion severity. The PLSS is the sum of the erythema, scaling and plaque thickness scores. The total PLSS score ranged from 0 (no symptom) to 12 (very marked). Each lesion must have a PLSS score of >=5. Due to major Baseline imbalances in psoriasis Baseline characteristics between the BID and TID groups, placebo BID and placebo TID arms were reported separately for all efficacy analyses. | Safety Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Scores on a scale | Days 1, 15, 29, 43, 57, 71 and 85 |
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| 0 |
| 18 |
| 0 |
| 18 |
| 8 |
| 18 |
| EG001 | GSK2982772 60 mg BID | Eligible participants received GSK2982772, 60 mg orally BID for 12 weeks in Cohort 1 of the study. | 1 | 23 | 1 | 23 | 21 | 23 |
| EG002 | GSK2982772 60 mg TID | Eligible participants received GSK2982772, 60 mg orally TID for 12 weeks in Cohort 2 of the study. | 0 | 24 | 1 | 24 | 16 | 24 |
| Procedural hypertension | Injury, poisoning and procedural complications | MedDRA20.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA20.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA20.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA20.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA20.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA20.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA20.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA20.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA20.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA20.1 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA20.1 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA20.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA20.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA20.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA20.1 | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA20.1 | Systematic Assessment |
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| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA20.1 | Systematic Assessment |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Measurements |
|---|---|
|
| ALT; To High |
|
| Albumin; To Low |
|
| Albumin; To Normal or No Change |
|
| Albumin; To High |
|
| Alkaline phosphatase; To Low |
|
| Alkaline phosphatase; To Normal or No Change |
|
| Alkaline phosphatase; To High |
|
| AST; To Low |
|
| AST; To Normal or No Change |
|
| AST; To High |
|
| Calcium; To Low |
|
| Calcium; To Normal or No Change |
|
| Calcium; To High |
|
| Creatinine; To Low |
|
| Creatinine; To Normal or No Change |
|
| Creatinine; To High |
|
| Glucose; To Low |
|
| Glucose; To Normal or No Change |
|
| Glucose; To High |
|
| Potassium; To Low |
|
| Potassium; To Normal or No Change |
|
| Potassium; To High |
|
| Sodium; To Low |
|
| Sodium; To Normal or No Change |
|
| Sodium; To High |
|
| Total bilirubin; To Low |
|
| Total bilirubin; To Normal or No Change |
|
| Total bilirubin; To High |
|
|
| Hematocrit; To High |
|
| Hemoglobin; To Low |
|
| Hemoglobin; To Normal or No Change |
|
| Hemoglobin; To High |
|
| Lymphocytes; To Low |
|
| Lymphocytes; To Normal or No Change |
|
| Lymphocytes; To High |
|
| Neutrophil count; To Low |
|
| Neutrophil count; To Normal or No Change |
|
| Neutrophil count; To High |
|
| Platelet count; To Low |
|
| Platelet count; To Normal or No Change |
|
| Platelet count; To High |
|
| White Blood Cell count; To Low |
|
| White Blood Cell count; To Normal or No Change |
|
| White Blood Cell count; To High |
|
| DAY 15; n=17, 21, 22 |
|
|
| DAY 43; n=16, 21, 21 |
|
|
| DAY 85; n=14, 21, 22 |
|
|
| FOLLOW UP (Day 116); n=16, 22, 24 |
|
|
| DAY 15; n=17, 21, 22 |
|
|
| DAY 43; n=16, 21, 21 |
|
|
| DAY 85; n=14, 21, 22 |
|
|
| FOLLOW UP (Day 116); n=16, 22, 24 |
|
|
| SBP; DAY 15; n=17, 22, 24 |
|
|
| SBP; DAY 29; n=16, 22, 24 |
|
|
| SBP; DAY 43; n=16, 21, 23 |
|
|
| SBP; DAY 57; n=14, 21, 22 |
|
|
| SBP; DAY 71; n=14, 21, 22 |
|
|
| SBP; DAY 85; n=14, 21, 22 |
|
|
| SBP; FOLLOW UP (Day 116); n=16, 22, 24 |
|
|
| DBP; DAY 8; n=18, 23, 24 |
|
|
| DBP; DAY 15; n=17, 22, 24 |
|
|
| DBP; DAY 29; n=16, 22, 24 |
|
|
| DBP; DAY 43; n=16, 21, 23 |
|
|
| DBP; DAY 57; n=14, 21, 22 |
|
|
| DBP; DAY 71; n=14, 21, 22 |
|
|
| DBP; DAY 85; n=14, 21, 22 |
|
|
| DBP; FOLLOW UP (Day 116); n=16, 22, 24 |
|
|
| DAY 15; n=17, 22, 24 |
|
|
| DAY 29; n=16, 22, 24 |
|
|
| DAY 43; n=16, 21, 23 |
|
|
| DAY 57; n=14, 21, 22 |
|
|
| DAY 71; n=14, 21, 22 |
|
|
| DAY 85; n=14, 21, 22 |
|
|
| FOLLOW UP (Day 116); n=16, 22, 24 |
|
|
| DAY 15; n=17, 22, 24 |
|
|
| DAY 29; n=16, 22, 24 |
|
|
| DAY 43; n=16, 21, 23 |
|
|
| DAY 57; n=14, 21, 22 |
|
|
| DAY 71; n=14, 21, 22 |
|
|
| DAY 85; n=14, 21, 22 |
|
|
| FOLLOW UP (Day 116); n=16, 22, 24 |
|
|
| DAY 15; n=17, 22, 24 |
|
|
| DAY 29; n=16, 22, 24 |
|
|
| DAY 43; n=16, 21, 23 |
|
|
| DAY 57; n=14, 21, 22 |
|
|
| DAY 71; n=14, 21, 22 |
|
|
| DAY 85; n=14, 21, 22 |
|
|
| FOLLOW UP (Day 116); n=16, 22, 24 |
|
|
| Title | Measurements |
|---|---|
|
| Abnormal-CS |
|
| Day 85; n=20, 22 |
|
|
| 2 Hours Post-dose; Day 1; n=22, 24 |
|
|
| 4 Hours Post-dose; Day 1; n=22, 24 |
|
|
| 6 Hours Post-dose; Day 1; n=22, 24 |
|
|
| 1 Hour Post-dose; Day 43; n=20, 23 |
|
|
| 2 Hours Post-dose; Day 43; n=20, 23 |
|
|
| 4 Hours Post-dose; Day 43; n=20, 23 |
|
|
| 6 Hours Post-dose; Day 43; n=20, 23 |
|
|
|
| CD11+; Epidermis; n=4 ,6, 10, 20 |
|
|
| CD161+; Dermis; n=7, 7, 13, 23 |
|
|
| CD161+; CD161+; Epidermis; n=1, 2 ,0, 4 |
|
|
| CD3+; Dermis; n=8 ,7, 20, 23 |
|
|
| CD3+; Epidermis; n=8, 7, 20, 23 |
|
|
| Elastase; Dermis; n=6, 5, 17, 19 |
|
|
| Elastase; Epidermis; n=4, 4, 4, 9 |
|
|
| No change |
|
| Positive to negative |
|
| Data missing |
|
|
| Interferon gamma; Day 43; n=8, 7, 21, 22 |
|
|
| Interleukin 10; Day 1; n=10,8,22,24 |
|
|
| Interleukin 10; Day 43; n=8, 7, 21, 22 |
|
|
| Interleukin 17A; Day 1; n=10,8,22,24 |
|
|
| Interleukin 17A; Day 43; n=8, 7, 21, 22 |
|
|
| Interleukin 21; Day 1; n=10,8,22,24 |
|
|
| Interleukin 21; Day 43; n=8, 7, 20, 22 |
|
|
| Interleukin 22; Day 1; n=10,8,22,24 |
|
|
| Interleukin 22; Day 43; n=8, 7, 21, 22 |
|
|
| Interleukin 23 subunit alpha; Day 1; n=10,8,22,24 |
|
|
| Interleukin 23 subunit alpha; Day 43; n=8,7,21,22 |
|
|
| Interleukin 4; Day 1; n=10,8,22,24 |
|
|
| Interleukin 4; Day 43; n=7, 7, 21, 22 |
|
|
| Tumor necrosis factor; Day 1; n=10,8,22,24 |
|
|
| Tumor necrosis factor; Day 43; n=8, 7, 21, 22 |
|
|
|
| DAY 29; n=9, 7, 22, 24 |
|
|
| DAY 43; n=9, 7, 21, 23 |
|
|
| DAY 57; n=8, 6, 21, 22 |
|
|
| DAY 71; n=7, 7, 21 ,22 |
|
|
| DAY 85; n=7, 7, 21 ,22 |
|
|
|
| DAY 15; n=10, 7, 22, 24 |
|
|
| DAY 29; n=9, 7, 22, 24 |
|
|
| DAY 43; n=9, 7, 21, 23 |
|
|
| DAY 57; n=8, 6, 21, 22 |
|
|
| DAY 71; n=7, 7, 21, 22 |
|
|
| DAY 85; n=7 ,7 ,21, 22 |
|
|