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GSK2982772

Phase 2

Psoriasis | Small molecule | Immunology |GSK plc|Last Updated: Mar 18, 2024

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials2
Total Enrollment94
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02776033Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Repeat Doses of GSK2982772 in Subjects With PsoriasisPHASE2 COMPLETED 65Aug 30, 2016Jan 4, 2018Jul 8, 20204 Canada
NCT04316585A Study to Evaluate the Benefit and Safety of GSK2982772 in Moderate to Severe Psoriasis ParticipantsPHASE1 COMPLETED 29Sep 28, 2020Oct 12, 2021Mar 18, 20249 Canada, Poland
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Study Endpoints
Primary Endpoints
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
Up to Day 116

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.

Number of Participants With Worst-case Post-Baseline Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria
Up to Day 116

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.

Number of Participants With Worst-case Post-Baseline Hematology Results by PCI Criteria
Up to Day 116

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.

Change From Baseline in Urine Potential of Hydrogen (pH)
Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116)

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.

Change From Baseline in Urine Specific Gravity
Baseline (Pre-dose on Day 1), Day 8, Day 15, Day 43, Day 85 and Follow-up (Day 116)

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.

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
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)

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.

Change From Baseline in Heart Rate
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)

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.

Change From Baseline in Respiratory Rate
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)

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.

Change From Baseline in Body Temperature
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)

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.

Number of Participants With Any Time Post-Baseline Results for Electrocardiogram Findings
Up to Day 116

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.

Percentage (%) of Participants Who Achieved Greater Than or Equal (>=) to 75% Improvement From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 12
Baseline and Week 12

The Psoriasis area severity index (PASI) is a standard tool for assessing the severity of psoriasis that considers the overall severity of erythema, induration, and scaling (each scored separately), and the extent of body surface area (BSA) affected with psoriasis. The 3 clinical signs are each graded on a 5-point scale (0=none to 4=severe) and the percent BSA affected is scored on a 7-point scale (0= 0% skin with psoriasis to 6= ≥ 90% skin with psoriasis). The individual scores are multiplied by a weighted factor for each body region; the sum of these scores gives the overall PASI score. The PASI is a composite scoring assessed by the investigator for the severity of lesions and the area affected into a single score with a range of 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Note: The 95% credible interval (CrI) was reported as a method of dispersion.

Secondary Endpoints
Plasma Concentrations of GSK2982772 at Days 43 and 85
Day 43 (Pre-dose) and Day 85
Post-dose Plasma Concentrations of GSK2982772 on Days 1 and 43
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
Baseline (Pre-dose on Day 1) and Day 43
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
GSK2982772 receivers in Cohort 1EXPERIMENTALRandomized subjects will receive GSK2982772 BID (approximately 12 hours apart) via oral route for 84 days.
Placebo receivers in Cohort 1PLACEBO_COMPARATORRandomized subjects will receive placebo BID via oral route for 84 days.
GSK2982772 receivers in Cohort 2EXPERIMENTALRandomized subjects will receive GSK2982772 TID (approximately 8 hours apart) via oral route for 84 days
Placebo receivers in Cohort 2PLACEBO_COMPARATORRandomized subjects will receive placebo TID via oral route for 84 days.
Participants receiving GSK2982772 960 mgEXPERIMENTALParticipants will receive GSK2982772 960 mg oral tablets once daily for 12 weeks.
Participants receiving placeboPLACEBO_COMPARATORParticipants will receive GSK2982772 matching placebo oral tablets once daily for 12 weeks.
Interventions
NameTypeDescription
GSK2982772DRUGGSK2982772 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.
PlaceboDRUGMatching 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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Eligibility Criteria
Age Range18 Years — 75 Years
SexALL
Healthy VolunteersNo
Study Sites4

Inclusion Criteria: * Between 18 and 75 years of age inclusive, at the time of signing the informed consent. * Subjects who do not have any medical conditions, other than active plaque-type psoriasis, that in the opinion of the Investigator put the subject at unacceptable risk or interfere with stu...

Countries:CanadaPoland
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