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GSK2831781

Phase 1

Psoriasis | Monoclonal antibody | Immunology |GSK plc|Last Updated: Mar 25, 2021

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-BlindCONTROLLEDBiomarker
Total Trials1
Total Enrollment67
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02195349A First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Intravenous (IV) Dose of GSK2831781 in Healthy Volunteers and Patients With Plaque PsoriasisPHASE1 COMPLETED 67Jul 30, 2014Mar 7, 2018Mar 25, 20213 Germany, United Kingdom
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Study Endpoints
Primary Endpoints
Number of Participants With Hematology Abnormalities of Potential Clinical Importance (PCI)
Up to 307 days

Hematology parameters with PCI ranges: hematocrit (high: \>0.54 percentage of red blood cells), hemoglobin (high: \>180 grams per liter \[g/L\]), lymphocytes (low: \<0.8\*giga cells per liter \[10\^9/L\]), neutrophil count (low: \<1.5\*10\^9/L), platelet count (low: \<100\*10\^9/L and high: \>550\*10\^9/L), and while blood cell count (low: \<3\*10\^9/L and high: \>20\*10\^9/L) for healthy volunteers and psoriasis participants. Safety population consisted of all randomized participants who received at least one dose of study treatment. Only those participants for which at least one value of PCI was reported are summarized.

Number of Participants With Clinical Chemistry Abnormalities of PCI
Up to 307 days

Clinical chemistry parameters and their potential clinical concern values: albumin (low: \<30 millimoles per liter \[mmol/L\]), calcium (low: \<2 mmol/L, high: \>2.75 mmol/L), creatinine (high: \>44.2 mmol/L), glucose (low: \<3 mmol/L, high: \>9 mmol/L), magnesium (low: \<0.5 mmol/L, high: \>1.23 mmol/L), phosphorus (low: \<0.8 mmol/L, high: \>1.6 mmol/L), potassium (low: \<3 mmol/L, high: \>5.5 mmol/L), sodium (low: \<130 mmol/L, high: \>150 mmol/L), and total carbon dioxide (CO2) (low: \<18 mmol/L, high: \>32 mmol/L). Number of participants with clinical chemistry of PCI are presented.

Number of Participants With Vital Signs of PCI
Up to 307 days

Vital signs included heart rate, systolic and diastolic blood pressure and body temperature were performed with the participant in a semi-supine position after the participant had rested for at least 5 minutes. The PCI range for heart rate (low: \<40 beats per minute \[BPM\] and high: \>110 BPM), systolic blood pressure (low: \<85 and high: \>160 millimeter of mercury \[mmHg\]), diastolic blood pressure (low: \<45 mmHg and high: \>100 mmHg) and body temperature (low: \<35 degree Celsius and high: \>37.5 degree Celsius). Number of participants with vital signs of PCI are presented.

Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) of PCI
Up to 307 days

Triplicate ECG was measured in a semi-supine position after 5 minutes rest. A single 12-lead ECG was obtained by using an ECG machine that automatically calculates heart rate and measured PR, QRS, QT, and Fridericia's formula (QTcF) intervals. The PCI ranges for QTc Interval (high: \>450 millisecond \[msec\]), PR Interval (low: \<110 msec and high: \>220 msec) and QRS Interval (low: \<75 msec and high: \>110 msec). Number of participants with ECG values of PCI are presented.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Up to 307 days

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 study treatment. A 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 disability/incapacity, is a congenital anomaly/birth defect and other important medical events judged by the investigator that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.

Change From Baseline in Interleukin (IL)-6, IL-8, Interferon-gamma, and Tumor Necrosis Factor (TNF) Alpha
Baseline, 6, 12, 24 and 48 hours post-dose

IL-6, IL-8, interferon-gamma and TNF alpha were assessed at indicated time points. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day 1, pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Number of Participants With Abnormal Values on Urinalysis by Dipstick in Placebo Healthy Volunteers
6, 12, 72, 168 hours, Days 15, 22, 29, 43, 57, 85, 121 and 191

Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, leucocytes, nitrites and ketones by dipstick. Urine dipstick tests were either read as qualitative concentrations as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present); or as semi quantitative cell counts or concentrations (0, 0.25, 0.5, 1.5,5, 7, 9, 10, 25, 50, 150, 250) where units depend on the test performed; (cells/micro liter for blood and leucocytes; mmol/L for glucose and ketones; g/L for protein), and Negative (not detected) or Positive (detected) for nitrites. For each methodology, abnormal results were defined as those that were not 'Negative' or 'Trace'. Only categories with abnormal urinalysis values are presented.

Number of Participants With Abnormal Values on Urinalysis by Dipstick for GSK2831781 0.0003 mg/kg (ADA-ve)
6, 12, 72, 168 hours, Day 15 and 29

Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, leucocytes, nitrites and ketones by dipstick. Urine dipstick tests were either read as qualitative concentrations as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present); or as semi quantitative cell counts or concentrations (0, 0.25, 0.5, 1.5,5, 7, 9, 10, 25, 50, 150, 250) where units depend on the test performed; (cells/micro liter for blood and leucocytes; mmol/L for glucose and ketones; g/L for protein), and Negative (not detected) or Positive (detected) for nitrites. For each methodology, abnormal results were defined as those that were not 'Negative' or 'Trace'. Only categories with abnormal urinalysis values are presented.

Number of Participants With Abnormal Values on Urinalysis by Dipstick for GSK2831781 0.0015 mg/kg (ADA-ve)
6, 12, 72, 168 hours, Days 15, 29 and 43

Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, leucocytes, nitrites and ketones by dipstick. Urine dipstick tests were either read as qualitative concentrations as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present); or as semi quantitative cell counts or concentrations (0, 0.25, 0.5, 1.5,5, 7, 9, 10, 25, 50, 150, 250) where units depend on the test performed; (cells/micro liter for blood and leucocytes; mmol/L for glucose and ketones; g/L for protein), and Negative (not detected) or Positive (detected) for nitrites. For each methodology, abnormal results were defined as those that were not 'Negative' or 'Trace'. Only categories with abnormal urinalysis values are presented.

Number of Participants With Abnormal Values on Urinalysis by Dipstick for GSK2831781 0.0075 mg/kg (ADA-ve)
6, 12, 72, 168 hours, Days 15, 22, 29, 43, 57 and 85

Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, leucocytes, nitrites and ketones by dipstick. Urine dipstick tests were either read as qualitative concentrations as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present); or as semi quantitative cell counts or concentrations (0, 0.25, 0.5, 1.5,5, 7, 9, 10, 25, 50, 150, 250) where units depend on the test performed; (cells/micro liter for blood and leucocytes; mmol/L for glucose and ketones; g/L for protein), and Negative (not detected) or Positive (detected) for nitrites. For each methodology, abnormal results were defined as those that were not 'Negative' or 'Trace'. Only categories with abnormal urinalysis values are presented.

Number of Participants With Abnormal Values on Urinalysis by Dipstick for GSK2831781 0.04 mg/kg (ADA-ve)
6, 12, 72, 168 hours, Days 15, 22, 29, 43, 57, 85, 121 and 147

Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, leucocytes, nitrites and ketones by dipstick. Urine dipstick tests were either read as qualitative concentrations as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present); or as semi quantitative cell counts or concentrations (0, 0.25, 0.5, 1.5,5, 7, 9, 10, 25, 50, 150, 250) where units depend on the test performed; (cells/micro liter for blood and leucocytes; mmol/L for glucose and ketones; g/L for protein), and Negative (not detected) or Positive (detected) for nitrites. For each methodology, abnormal results were defined as those that were not 'Negative' or 'Trace'. Only categories with abnormal urinalysis values are presented.

Number of Participants With Abnormal Values on Urinalysis by Dipstick for GSK2831781 0.15 mg/kg (ADA-ve)
6, 12, 72, 168 hours, Days 15, 22, 29, 43, 57, 85, 121 and 219

Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, leucocytes, nitrites and ketones by dipstick. Urine dipstick tests were either read as qualitative concentrations as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present); or as semi quantitative cell counts or concentrations (0, 0.25, 0.5, 1.5,5, 7, 9, 10, 25, 50, 150, 250) where units depend on the test performed; (cells/micro liter for blood and leucocytes; mmol/L for glucose and ketones; g/L for protein), and Negative (not detected) or Positive (detected) for nitrites. For each methodology, abnormal results were defined as those that were not 'Negative' or 'Trace'. Only categories with abnormal urinalysis values are presented.

Number of Participants With Abnormal Values on Urinalysis by Dipstick for GSK2831781 0.15 mg/kg (ADA+ve)
6, 12, 72, 168 hours, Days 15, 22, 29, 43, 57, 85, 121 and 191

Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, leucocytes, nitrites and ketones by dipstick. Urine dipstick tests were either read as qualitative concentrations as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present); or as semi quantitative cell counts or concentrations (0, 0.25, 0.5, 1.5,5, 7, 9, 10, 25, 50, 150, 250) where units depend on the test performed; (cells/micro liter for blood and leucocytes; mmol/L for glucose and ketones; g/L for protein), and Negative (not detected) or Positive (detected) for nitrites. For each methodology, abnormal results were defined as those that were not 'Negative' or 'Trace'. Only categories with abnormal urinalysis values are presented.

Number of Participants With Abnormal Values on Urinalysis by Dipstick for Psoriasis Placebo
6, 12, 72, 168 hours, Days 15, 22, 29, 43, 57, 85, 121 and 307

Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, leucocytes, nitrites and ketones by dipstick. Urine dipstick tests were either read as qualitative concentrations as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present); or as semi quantitative cell counts or concentrations (0, 0.25, 0.5, 1.5,5, 7, 9, 10, 25, 50, 150, 250) where units depend on the test performed; (cells/micro liter for blood and leucocytes; mmol/L for glucose and ketones; g/L for protein), and Negative (not detected) or Positive (detected) for nitrites. For each methodology, abnormal results were defined as those that were not 'Negative' or 'Trace'. Only categories with abnormal urinalysis values are presented.

Number of Participants With Abnormal Values on Urinalysis by Dipstick for GSK2831781 0.5 mg/kg
6, 12, 72, 168 hours, Days 15, 22, 29, 43, 57, 85, 121 and 237

Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, leucocytes, nitrites and ketones by dipstick. Urine dipstick tests were either read as qualitative concentrations as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present); or as semi quantitative cell counts or concentrations (0, 0.25, 0.5, 1.5,5, 7, 9, 10, 25, 50, 150, 250) where units depend on the test performed; (cells/micro liter for blood and leucocytes; mmol/L for glucose and ketones; g/L for protein), and Negative (not detected) or Positive (detected) for nitrites. For each methodology, abnormal results were defined as those that were not 'Negative' or 'Trace'. Only categories with abnormal urinalysis values are presented.

Number of Participants With Abnormal Values on Urinalysis by Dipstick for GSK2831781 1.5 mg/kg
6, 12, 72, 168 hours, Days 15, 22, 29, 43, 57, 85, 121 and 277

Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, leucocytes, nitrites and ketones by dipstick. Urine dipstick tests were either read as qualitative concentrations as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present); or as semi quantitative cell counts or concentrations (0, 0.25, 0.5, 1.5,5, 7, 9, 10, 25, 50, 150, 250) where units depend on the test performed; (cells/micro liter for blood and leucocytes; mmol/L for glucose and ketones; g/L for protein), and Negative (not detected) or Positive (detected) for nitrites. For each methodology, abnormal results were defined as those that were not 'Negative' or 'Trace'. Only categories with abnormal urinalysis values are presented.

Number of Participants With Abnormal Values on Urinalysis by Dipstick for GSK2831781 5 mg/kg
6, 12, 72, 168 hours, Days 15, 22, 29, 43, 57, 85, 121 and 307

Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, leucocytes, nitrites and ketones by dipstick. Urine dipstick tests were either read as qualitative concentrations as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present); or as semi quantitative cell counts or concentrations (0, 0.25, 0.5, 1.5,5, 7, 9, 10, 25, 50, 150, 250) where units depend on the test performed; (cells/micro liter for blood and leucocytes; mmol/L for glucose and ketones; g/L for protein), and Negative (not detected) or Positive (detected) for nitrites. For each methodology, abnormal results were defined as those that were not 'Negative' or 'Trace'. Only categories with abnormal urinalysis values are presented.

Secondary Endpoints
Change From Baseline (PPD First Challenge) of Induration Diameter From Re-challenge at 3 Days Post-dose
Baseline, Days 4, 8, 15 and 22 post-dose
Duration of Induration in the Re-challenge for DTH
Up to 28 days post-dose
Change From Baseline (PPD First Challenge) of Lymphocyte Activation Gene-3 (LAG-3)+ Cells in Biopsies of Re-challenged Skin at 3 Days Post-dose
Baseline and 72 hours post-dose
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Healthy Subjects (no DTH)EXPERIMENTALOne subject will be dosed with GSK2831781 (0.0003 mg/kg) and one with placebo. Depending on the safety data obtained for 28 days post dose along with the available PK data, a dose escalation may be done to the next planned dose (0.0015 , 0.0075, 0.04, 0.15 mg/kg). In case safety findings are noted then the cohort may be expanded to a maximum cohort size of 6:3 (GSK2831781: placebo) or the escalation will be stopped.
Healthy Subjects (DTH)EXPERIMENTALSentinel subjects (one dosed with GSK2831781 (0.0003 mg/kg) and one with placebo) will be used in the cohort. Following a review of safety data up to 48 hours post dose, an additional 5 active (GSK2831781) and 1 placebo subject will be dosed (no more than 2 subjects per day with dosing separated by at least 1 hour). After reviewing the safety data for 28 days the healthy subjects (DTH) will be escalated to the planned dose of GSK2831781 (0.0075, 0.04, 0.15 mg/kg) in 6:3 ratio with placebo.
Subjects with PsoriasisEXPERIMENTALSentinel subjects (one dosed with GSK2831781 and one with placebo) will be used in the cohort. Following a review of safety data up to 48 hours post dose, an additional 5 active (GSK2831781) and 2 placebo subjects will be dosed (no more than 2 subjects per day with dosing separated by at least 1 hour). All subsequent cohorts do not require stratification for pre-existing ADAs. After reviewing the safety data for 28 days for minimum of 8 out of 9 subjects within the cohort and all subjects have completed dosing and the inpatient monitoring until Day 4, the subjects with psoriasis will be escalated to the planned dose of GSK2831781 (1.5 and 5 mg/kg) in 6:3 ratio with placebo.
Interventions
NameTypeDescription
GSK2831781BIOLOGICALGSK2831781 (100 milligram (mg)/mL) and its dilutions (Diluent - 0.9 percent saline solution containing 0.015 percent Polysorbate 80) as clear or opalescent, colourless, yellow to brown liquid solution administered by IV over approximately 2 hours.
PlaceboBIOLOGICALCommercial saline solution administered by IV over approximately 2 hours
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Eligibility Criteria
Age Range18 Years — 75 Years
SexALL
Healthy VolunteersYes
Study Sites3

Inclusion Criteria: * Part A males aged between 18 and 65 years of age and Part B males and females aged between 18 and 75 years of age inclusive, at the time of signing the informed consent * Part A: A body weight \<=120 kilogram (kg) and Body mass index (BMI) within the range 19-32 kg/square mete...

Countries:GermanyUnited Kingdom
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