Efficacy, Safety, Tolerability and Pharmacokinetic (PK) Study of GSK1070806 for the Prevention of Delayed Graft Function (DGF) in Adult Subjects After Renal Transplantation

A Phase 2 Pilot, Multicenter, Single Arm Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of GSK1070806 Plus Standard of Care for the Prevention of Delayed Graft Function in Adult Subjects After Renal Transplantation

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02723786

Enrollment

Registered

2016-03-30

Start date

2016-08-27

Completion date

2018-03-06

Last updated

2019-06-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Kidney Transplantation (Status Post)

Keywords

Delayed Graft Function, Renal Transplantation, Prevention, GSK1070806

Brief summary

This is a phase 2 study to evaluate the efficacy, safety, tolerability and pharmacokinetics of GSK1070806 in subjects undergoing renal transplantation. GSK1070806 is an anti-interleukin 18 (IL18) monoclonal antibody, which binds to IL-18 and inhibits signaling through the IL-18 receptor. Recipients of donor kidneys, retrieved after circulatory death of the donor, will be administered a single intravenous infusion of GSK1070806 to test whether inhibition of IL-18 can reduce the rate of Delayed Graft Function (DGF) and graft rejection. Subjects will be followed for 12 months post dose/transplant. Up to 40 adult subjects will be enrolled in this study.

Interventions

BIOLOGICALGSK1070806

Injectable solution of 100 milligram/millilitre (mg/mL), administered as a single dose of 3 milligram/kilogram (mg/kg) (maximum of 10 mg/kg) diluted in 100 mL sterile IV infusion bag of 0.9% Sodium Chloride.

DRUG1) basiliximab 2) mycophenolate mofetil (MMF) OR azathioprine 3) tacrolimus 4) corticosteroids

This immunosuppressant regimen may be revised based on the clinical judgment of the investigator including titration of tacrolimus levels.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Recipient age range: Between 18 and 75 years of age inclusive, at the time of signing the informed consent. * Dialysis-dependent recipient of first time, single kidney-only, Donation after Circulatory Death (DCD) transplant. * Eligible for kidney transplantation: Considered eligible after undergoing multidisciplinary evaluation at the institution at which the transplantation will be performed. * Immunosuppressants (at the time of transplantation): planned to receive a combination of immunosuppressants including basiliximab, mycophenolate mofetil or azathioprine, tacrolimus, and corticosteroids. * Male and Female: 1. Males: Male subjects with female partners of child bearing potential must utilize a condom and female partners must comply with use of highly effective contraceptive methods for 180 days post-dose of study medication. 2. Females: * Non-reproductive potential defined as in the protocol. Reproductive potential: Must not be pregnant or lactating, 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) for 180 days post dose as defined in the protocol. * Capable of providing signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.

Exclusion criteria

* Liver function: Alanine Aminotransferase (ALT) \>2xUpper Limit of Normal (ULN) and bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * QT interval: single or average Corrected QT Interval (QTc)\>480 milliseconds (msec) or in subjects with bundle branch block QTc\>500 msec (these criteria do not apply to subjects with predominately paced rhythms). * Concurrent medication: Subjects who receive treatment that is prohibited for safety reasons (e.g. live vaccines, cyclophosphamide or other biologic immunosuppressants) should not receive investigational product without the explicit approval of the Medical Monitor (Sponsor). * Investigational product: Any within 5 half-lives or twice the duration of the biological effect whichever is longer (investigational product refers to any drug not approved for sale in the country in which it is being used). * Immunosuppression: Are being considered for steroid-free, anti-thymocyte globulin (ATG) or alemtuzumab induction, which have a much more profound and prolonged immunosuppressive effect than basiliximab. * Prior biologic immunosuppressives: The subject has received an agent within the following time period prior to the day of dosing in the current study: 30 days, 5 half-lives or twice the duration of the biological effect, whichever is longer. * Vaccines: A live vaccine within 30 days prior to GSK1070806 administration * Receiving a DCD kidney allograft from a donor with any of the following characteristics: cold ischemic time \>36 hours, age \<5 years old, age \>75 years old, ABO blood type incompatible against the recipient, T- and/or B-cell positive cross-match by complement dependent cytotoxicity or flow cytometry against the recipient (where positive cross-match is unavailable, virtual cross-match is allowed), serology positive for hepatitis B (except hepatitis B surface antibody and prior vaccination), hepatitis C or human immunodeficiency virus (HIV), Epstein Barr Virus (EBV) positive donor allograft with an EBV negative recipient, donor had acute or chronic bacterial, viral or fungal infection that according to the investigator causes a risk to recipient, particularly if the infection was resistant or systemic, normothermic regional machine perfusion organ retrieval techniques were utilized, surgical damage to donor allograft during organ procurement * Previous organ transplantation: has previously undergone any other organ transplantation (with the exception of corneal transplantation). * Malignancy: has a history of malignancy in the past 5 years except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix. * Acute or chronic infection: has required management of acute or chronic infections (excludes prophylaxis of infections), as follows: currently being treated for a chronic infection, which in the opinion of the investigator, could put the subject at undue risk; hospitalized for treatment of infection, or treated for an infection with parenteral antibiotics (includes antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 30 days before Day 0, which in the opinion of the investigator, could put the subject at undue risk; current evidence, or history within the last 14 days, of an influenza-like illness as defined by fever (\>38 degree Celsius) and two or more of the following symptoms: cough, sore throat, runny nose, sneezing, limb / joint pain, headache, vomiting / diarrhoea; subjects with any history of active tuberculosis, recent tuberculosis exposure, or judged by investigators to be at risk of tuberculosis will be excluded from the study. * Other disease/conditions. Has any of the following: clinical evidence of significant unstable or uncontrolled acute or chronic diseases, which in the opinion of the investigator, could confound the results of the study or put the subject at undue risk; a surgical procedure planned in the 12 months after Day 0, other than kidney transplantation or related procedure; a known history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the investigator, makes the subject unsuitable for the study * Hepatitis B: subjects will be excluded with any evidence of acute or chronic infection, or if interpretation of their results is unclear. This includes: Hepatitis B surface Antigen (HBsAg)+, Anti- Hepatitis B core (Anti-HBc)+, Hepatitis B Deoxyribose Nucleic Acid (HB DNA)+. It is permissible to enroll subjects who are anti-Hepatitis B (HB)s+ only, when this is attributable to vaccination and there is no history of previous infection. * Hepatitis C: subjects will be excluded if there is any evidence of past or current hepatitis C infection, including hepatitis C antibody, hepatitis C Recombinant ImmunoBlot Assay (RIBA) or Polymerase Chain Reaction (PCR). * HIV: known to have a historically positive HIV test. * Immunodeficiency: recipient with a history of, or laboratory evidence of immunodeficiency. * Drug Sensitivity: has a history of sensitivity to any of the study medications including: GSK1070806; background immunosuppressive regimen; designated prophylactic anti-infective therapies or components thereof, or a history of drug or other allergy including a previous anaphylactic reaction to parenteral administration or biologic therapy (ie monoclonal antibody) that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation. * Substance abuse: has clinical evidence of current drug or alcohol abuse or dependence. * Co enrollment: participating in another interventional study (participation in purely observational or cohort studies is acceptable provided they do not impair feasibility, or involve excessive additional sampling). * Compliance: is unlikely to comply with scheduled study visits based on investigator judgment or has a history of a psychiatric disorder or condition that may compromise communication with the investigator.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Requiring Dialysis During the First 7 Days Post Transplant	Up to Day 7	The requirement of dialysis (except as needed for hyperkalaemia during the first 24 hours \[hrs\]) were used to assess the frequency of delayed graft function (DGF) in donation after circulatory death (DCD) renal transplant recipients treated with GSK1070806. The 'Analysis Population' (AP) is defined as participants in the 'All Subjects' Population who have been declared to have DGF or have reached 7 days.

Secondary

Measure	Time frame	Description
Urine Volume at Baseline and Change From Baseline Over Time Post Transplant	Baseline (Pre-operative) and up to Day 28	Urine volume at Baseline and over time post transplant was measured to assess graft function in DCD renal transplant recipients treated with GSK1070806. Baseline value was the latest pre-dose assessment value. Change from Baseline was post Baseline value minus Baseline value. All Subjects Population comprised of participants who received the dose of study medication.
Number of Participants in the First 7 Days With: Primary Non Function, Functional DGF, Intermediate Graft Function, Immediate Graft Function	Up to Day 7	Number of participants in the first 7 days with primary non function, functional DGF, intermediate graft function and immediate graft function were evaluated to access graft function in DCD renal transplant recipients treated with GSK1070806. The AP Population is defined as participants in the 'All Subjects' Population who have been declared to have DGF or have reached 7 days.
Number of Participants With Episodes of Biopsy-proven Acute Rejection	Up to 12 months	Number of participants with episodes of biopsy-proven acute rejection were evaluated to assess the effect of GSK1070806 on acute rejection risk, and rejection/Pharmacodynamic (PD) biomarkers.
Serum Interferon Gamma-induced Protein 10 (IP-10) and Serum Monokine Induced Gamma Interferon (Mig) Levels at Baseline and Change From Baseline Over Time Post Transplant	Baseline and at 0.75 hours, 4-8 hours, Day 1, Day 2, Day 30, Day 90, 6 months and 12 months post reperfusion	The interferon-gamma -inducible chemokine IP10 and the interferon-gamma -inducible chemokine Mig have been identified as an early predictive marker of antibody-mediated kidney graft rejection. Baseline value was the latest pre-dose assessment value. Change from Baseline was calculated as post Baseline value minus Baseline value.
Number of Participants With Dialysis Events in the First 30 Days Post-transplant	Up to 30 days	Number of participants with dialysis events in the first 30 days post transplant was evaluated to assess the effect of GSK1070806 on dialysis dependency and graft survival. The AP Population is defined as participants having Baseline and at least one post-Baseline assessment.
Number of Participants Who Are Dialysis Independent at Visits up to 12 Months Post-transplant	Up to 12 months	Number of participants who are dialysis independent at visits up to 12 months post transplant was evaluated to assess the effect of GSK1070806 on dialysis dependency and graft survival.
Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE)	Up to 12 months	AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.
Number of Participants Having Any Abnormality in Hematology Results of Potential Clinical Importance	Up to 12 months	Blood samples were collected to evaluate hematology parameters. Number of participants with abnormality in any hematology parameter results of potential clinical importance (high or low) observed at any time post Baseline are presented. PCI (high or low) was considered if hematocrit (high:\>0.54;low:change from baseline \[CFB\] 0.075 decrease), hemoglobin (high:180; low: CFB 25 decrease), lymphocytes (low: 0.8), neutrophil count (low: 1.5), platelet count (low: 100; high: 550), White blood cells (low: 3; high:20).
Serum Creatinine at Baseline and Change From Baseline Over Time Post Transplant	Baseline and up to 12 months	Blood samples were collected to measure serum creatinine at the indicated timepoints to assess graft function in DCD renal transplant recipients treated with GSK1070806. Baseline value was the latest pre-dose assessment value. Change from Baseline was post Baseline value minus Baseline value. NA indicates data is not available as standard deviation could not be calculated due to n=1. The AP Population is defined as participants having Baseline and at least one post-Baseline assessment.
Number of Participants Having Any Abnormality of Potential Clinical Importance of Vital Signs Results	Up to 12 months	Vital signs parameters included analysis of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and body temperature. Number of participants with any abnormality of potential clinical importance (high or low) in any of these vitals signs at any time post Baseline visit have been presented. PCI (high or low) was considered if SBP (low: \<85, high:\>160), DBP (low: \<45, high\>100), HR (low: \<40, high: \>110) and temperature (low: \<35.5, high: \>37.5).
Number of Participants Having Infections	Up to 12 months	Number of participants having infections were summarized.
Serum Concentrations of GSK1070806	Pre-operative, 0.75 hours, 4-8 hours, 24 hours, 168 hours, Day 30, Day 90, 6 months and 12 months after kidney reperfusion	Serial blood samples were collected to evaluate PK of GSK1070806 at Pre-operative, 0.75 hours, 4-8 hours, 24 hours, 168 hours, Day 30, Day 90, 6 months and 12 months after kidney reperfusion. PK Population included participants in the 'All Subjects' Population for whom a serum PK sample is obtained and analyzed for GSK1070806.
Maximum Plasma Concentration (Cmax) of GSK1070806	Pre-operative, 0.75 hours, 4-8 hours, 24 hours, 168 hours, Day 30, Day 90, 6 months and 12 months after kidney reperfusion	Serial blood samples were collected to evaluate PK of GSK1070806 at Pre-operative, 0.75 hours, 4-8 hours, 24 hours, 168 hours, Day 30, Day 90, 6 months and 12 months after kidney reperfusion. Log-transformed geometric mean and 95% confidence interval have been presented.
Area Under the Plasma Concentration Time Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC[0-t]) and AUC From Time 0 to Infinite Time (AUC[0-inf]) of GSK1070806	Pre-operative, 0.75 hours, 4-8 hours, 24 hours, 168 hours, Day 30, Day 90, 6 months and 12 months after kidney reperfusion	Blood samples were collected to evaluate PK of GSK1070806 at Pre-operative, 0.75 hours, 4-8 hours, 24 hours, 168 hours, Day 30, Day 90, 6 months and 12 months after kidney reperfusion. Log-transformed geometric mean and 95% confidence interval have been presented.
Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Baseline and at 0.75 hours, 4-8 hours, Day 1, Day 2, Day 30, Day 90, 6 months and 12 months post reperfusion	IL-18 is itself rapidly secreted from intracellular stores following inflammasome mediated-activation. The appearance of IL-18 marks the initiation of the inflammatory response leading to further injury. Blood samples were collected at indicated time points to assess serum levels of free, total, and GSK1070806 bound IL-18. Baseline value was the latest pre-dose assessment value. Change from Baseline was post Baseline value minus Baseline value.
Number of Participants With Positive Result in Anti-GSK1070806 Antibodies (ADAs)	0.75 hour and 4-8 hour on Day 0, Day 1, Day 2, Day 30, Day 90, 6 months and 12 months post reperfusion	Serum samples were to be collected to test for the presence of antibodies against GSK1070806 at indicated time points. The presence of anti-GSK1070806 binding antibodies were to be assessed using a validated electrochemiluminescent (ECL) immunoassay.
ADA Titer Before and After GSK1070806 Administration	0.75 hour and 4-8 hour on Day 0, Day 1, Day 2, Day 30, Day 90, 6 months and 12 months post reperfusion	Serum samples were to be collected to test for the presence of antibodies against GSK1070806 at indicated time points. The presence of ADA titre was to be assessed using a validated ECL immunoassay.
Number of Participants Having Any Abnormal Clinical Chemistry Results of Potential Clinical Importance	Up to 12 months	Blood samples were collected to evaluate clinical chemistry parameters. Number of participants with abnormal chemistry results of potential clinical importance (high or low) in any of these parameters at any time post Baseline visit have been presented. PCI (high or low) was considered if albumin (low\<30), calcium (low\<2, high\>2.75), creatinine (high: CHB\>44.2 increase), glucose (low\<3, high\>9), magnesium (low\<0.5, high\>1.23), phosphorus (low\<0.8, high\>1.6), potassium (low\<3, high\>5.5), sodium (low: 130, high\>150), Total carbon dioxide (CO2) (low:18, high\>32), Alanine aminotransferase (ALT) (high\>=2\upper limit of normal \[ULN\]), Aspartate aminotransferase (AST) (high: \>=2\ULN), Alkaline phosphatase (ALP) (high:\>=2\ULN), Total bilirubin (high: \>2\ULN), Total bilirubin+ALT (high: 1.5\ULN total bilirubin with \>=2\ULN ALT).

Countries

Spain, United Kingdom

Participant flow

Recruitment details

This was a single arm study to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of GSK1070806 plus standard of care (SOC) for the prevention of delayed graft function in adult participants after renal transplantation.

Pre-assignment details

A total of 10 participants were screened for the study, and 7 of them received study treatment. The study enrolled participants in 4 centers across 2 countries (Spain and United Kingdom).

Participants by arm

Arm	Count
GSK1070806 3 mg/kg IV Participants received a single dose of 3 milligram per kilogram (mg/kg) intravenous (IV) infusion of GSK1070806 administered prior to kidney allograft reperfusion. Participants also received a combination immunosuppression comprised of basiliximab; mycophenolate mofetil (MMF) or aziothioprine; tacrolimus; and corticosteroids based on the clinical judgment of the investigator.	7
Total	7

Arm

Count

GSK1070806 3 mg/kg IV

Participants received a single dose of 3 milligram per kilogram (mg/kg) intravenous (IV) infusion of GSK1070806 administered prior to kidney allograft reperfusion. Participants also received a combination immunosuppression comprised of basiliximab; mycophenolate mofetil (MMF) or aziothioprine; tacrolimus; and corticosteroids based on the clinical judgment of the investigator.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	1

Baseline characteristics

Characteristic	GSK1070806 3 mg/kg IV
Age, Continuous	58.7 Years STANDARD_DEVIATION 13.46
Race/Ethnicity, Customized White	7 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	7 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 7
other Total, other adverse events	7 / 7
serious Total, serious adverse events	6 / 7

Outcome results

Primary

Number of Participants Requiring Dialysis During the First 7 Days Post Transplant

The requirement of dialysis (except as needed for hyperkalaemia during the first 24 hours \[hrs\]) were used to assess the frequency of delayed graft function (DGF) in donation after circulatory death (DCD) renal transplant recipients treated with GSK1070806. The 'Analysis Population' (AP) is defined as participants in the 'All Subjects' Population who have been declared to have DGF or have reached 7 days.

Time frame: Up to Day 7

Population: AP Population

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
GSK1070806 3 mg/kg IV	Number of Participants Requiring Dialysis During the First 7 Days Post Transplant	4 Participants

Secondary

ADA Titer Before and After GSK1070806 Administration

Serum samples were to be collected to test for the presence of antibodies against GSK1070806 at indicated time points. The presence of ADA titre was to be assessed using a validated ECL immunoassay.

Time frame: 0.75 hour and 4-8 hour on Day 0, Day 1, Day 2, Day 30, Day 90, 6 months and 12 months post reperfusion

Population: All Subjects Population. Data was not collected as the immunogenicity samples were not collected for this terminated indication since healthy volunteers showed low titers and Type 2 Diabetics showed no titers per Investigator's Brochure.

Secondary

Area Under the Plasma Concentration Time Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC[0-t]) and AUC From Time 0 to Infinite Time (AUC[0-inf]) of GSK1070806

Blood samples were collected to evaluate PK of GSK1070806 at Pre-operative, 0.75 hours, 4-8 hours, 24 hours, 168 hours, Day 30, Day 90, 6 months and 12 months after kidney reperfusion. Log-transformed geometric mean and 95% confidence interval have been presented.

Time frame: Pre-operative, 0.75 hours, 4-8 hours, 24 hours, 168 hours, Day 30, Day 90, 6 months and 12 months after kidney reperfusion

Population: PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
GSK1070806 3 mg/kg IV	Area Under the Plasma Concentration Time Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC[0-t]) and AUC From Time 0 to Infinite Time (AUC[0-inf]) of GSK1070806	AUC (0-t), n=7	26131338.2 Log (Hour*nanograms per milliliter)
GSK1070806 3 mg/kg IV	Area Under the Plasma Concentration Time Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC[0-t]) and AUC From Time 0 to Infinite Time (AUC[0-inf]) of GSK1070806	AUC (0-inf), n=6	41032450.7 Log (Hour*nanograms per milliliter)

Secondary

Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant

IL-18 is itself rapidly secreted from intracellular stores following inflammasome mediated-activation. The appearance of IL-18 marks the initiation of the inflammatory response leading to further injury. Blood samples were collected at indicated time points to assess serum levels of free, total, and GSK1070806 bound IL-18. Baseline value was the latest pre-dose assessment value. Change from Baseline was post Baseline value minus Baseline value.

Time frame: Baseline and at 0.75 hours, 4-8 hours, Day 1, Day 2, Day 30, Day 90, 6 months and 12 months post reperfusion

Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Free IL-18, Baseline (pre-operative), n=5	26.840 Picograms per milliliter	Standard Deviation 37.0569
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Free IL-18, Day 0, 0.75 hour, n=5	-22.620 Picograms per milliliter	Standard Deviation 37.1672
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Free IL-18, Day 0, 4-8 hour, n=5	-22.540 Picograms per milliliter	Standard Deviation 34.1535
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Free IL-18, Day 1, n=5	-23.890 Picograms per milliliter	Standard Deviation 37.0569
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Free IL-18, Day 2, n=4	-5.263 Picograms per milliliter	Standard Deviation 14.4846
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Free IL-18, Day 30, n=4	-27.925 Picograms per milliliter	Standard Deviation 41.5019
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Free IL-18, Day 90, n=2	-2.250 Picograms per milliliter	Standard Deviation 3.182
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Bound IL-18, Baseline (pre-operative), n=5	21.156 Picograms per milliliter	Standard Deviation 7.5139
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Bound IL-18, Day 0, 0.75 hour, n=5	362.084 Picograms per milliliter	Standard Deviation 220.2164
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Bound IL-18, Day 0, 4-8 hour, n=5	314.864 Picograms per milliliter	Standard Deviation 139.1919
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Bound IL-18, Day 1, n=5	472.204 Picograms per milliliter	Standard Deviation 193.0366
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Bound IL-18, Day 2, n=4	485.740 Picograms per milliliter	Standard Deviation 252.2876
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Bound IL-18, Day 30, n=4	617.543 Picograms per milliliter	Standard Deviation 282.9679
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Bound IL-18, Day 90, n=2	946.020 Picograms per milliliter	Standard Deviation 21.3971
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Total IL-18, Baseline (pre-operative), n=7	130.6857 Picograms per milliliter	Standard Deviation 71.37029
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Total IL-18, Day 0, 0.75 hour, n=6	572.3333 Picograms per milliliter	Standard Deviation 368.6862
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Total IL-18, Day 0, 4-8 hour, n=6	576.3667 Picograms per milliliter	Standard Deviation 273.88543
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Total IL-18, Day 1, n=6	636.5667 Picograms per milliliter	Standard Deviation 208.88294
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Total IL-18, Day 2, n=5	660.6600 Picograms per milliliter	Standard Deviation 297.32305
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Total IL-18, Day 30, n=6	1175.5000 Picograms per milliliter	Standard Deviation 710.48323
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Total IL-18, Day 90, n=7	1423.5429 Picograms per milliliter	Standard Deviation 685.42012
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Total IL-18, 6 months, n=7	1303.7143 Picograms per milliliter	Standard Deviation 1006.89585
GSK1070806 3 mg/kg IV	Baseline and Change From Baseline in Serum Levels of Free, Total, and GSK1070806 Bound Interleukin 18 (IL-18) Over Time Post-transplant	Serum Total IL-18, 12 months, n=6	1091.0833 Picograms per milliliter	Standard Deviation 1102.78861

Secondary

Maximum Plasma Concentration (Cmax) of GSK1070806

Serial blood samples were collected to evaluate PK of GSK1070806 at Pre-operative, 0.75 hours, 4-8 hours, 24 hours, 168 hours, Day 30, Day 90, 6 months and 12 months after kidney reperfusion. Log-transformed geometric mean and 95% confidence interval have been presented.

Time frame: Pre-operative, 0.75 hours, 4-8 hours, 24 hours, 168 hours, Day 30, Day 90, 6 months and 12 months after kidney reperfusion

Population: PK Population

Arm	Measure	Value (GEOMETRIC_MEAN)
GSK1070806 3 mg/kg IV	Maximum Plasma Concentration (Cmax) of GSK1070806	36315.1 Log (nanograms per milliliter)

Secondary

Number of Participants Having Any Abnormal Clinical Chemistry Results of Potential Clinical Importance

Blood samples were collected to evaluate clinical chemistry parameters. Number of participants with abnormal chemistry results of potential clinical importance (high or low) in any of these parameters at any time post Baseline visit have been presented. PCI (high or low) was considered if albumin (low\<30), calcium (low\<2, high\>2.75), creatinine (high: CHB\>44.2 increase), glucose (low\<3, high\>9), magnesium (low\<0.5, high\>1.23), phosphorus (low\<0.8, high\>1.6), potassium (low\<3, high\>5.5), sodium (low: 130, high\>150), Total carbon dioxide (CO2) (low:18, high\>32), Alanine aminotransferase (ALT) (high\>=2\*upper limit of normal \[ULN\]), Aspartate aminotransferase (AST) (high: \>=2\*ULN), Alkaline phosphatase (ALP) (high:\>=2\*ULN), Total bilirubin (high: \>2\*ULN), Total bilirubin+ALT (high: 1.5\*ULN total bilirubin with \>=2\*ULN ALT).

Time frame: Up to 12 months