Efficacy, Safety, Tolerability and Pharmacokinetic (PK) S... | NCT02723786

ID	Type	Description	Link
2015-002812-33	EudraCT Number

Label	Type	Description	Intervention Names
GSK1070806 3 mg/kg IV	Experimental	Subjects received a single dose of 3 milligram per kilogram (mg/kg) intravenous (IV) infusion of GSK1070806 administered prior to kidney allograft reperfusion. Subjects also received a combination immunosuppression comprized of basiliximab; mycophenolate mofetil (MMF) or aziothioprine; tacrolimus; and corticosteroids based on the clinical judgment of the investigator.	Biological: GSK1070806 Drug: 1) basiliximab 2) mycophenolate mofetil (MMF) OR azathioprine 3) tacrolimus 4) corticosteroids

Name	Type	Description	Arm Group Labels	Other Names
GSK1070806	Biological	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.

Measure	Description	Time Frame
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.	Up to Day 7

Measure	Description	Time Frame
Serum Creatinine at Baseline and Change From Baseline Over Time Post Transplant	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.

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		L'Hospitalet de Llobregat		08907	Spain
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
33684160	Derived	Wlodek E, Kirkpatrick RB, Andrews S, Noble R, Schroyer R, Scott J, Watson CJE, Clatworthy M, Harrison EM, Wigmore SJ, Stevenson K, Kingsmore D, Sheerin NS, Bestard O, Stirnadel-Farrant HA, Abberley L, Busz M, DeWall S, Birchler M, Krull D, Thorneloe KS, Weber A, Devey L. A pilot study evaluating GSK1070806 inhibition of interleukin-18 in renal transplant delayed graft function. PLoS One. 2021 Mar 8;16(3):e0247972. doi: 10.1371/journal.pone.0247972. eCollection 2021.

ID	Title	Description
FG000	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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	May 24, 2017	Mar 8, 2018

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG0007

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 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.

AP Population

Posted

Count of Participants

Participants

Up to Day 7

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG0007

Title

Denominators

Categories

Title	Measurements
	OG0004

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000																		Other		The proportion of participants with DGF was 0.57, highest Posterior Density (HPD) 95% Credible interval (CI) (0.25,0.90). The posterior probability for the proportion of participants with DGF <30% was 0.07 (HPD 95% CI [0.00,1.00]). The posterior probability for the proportion of participants with DGF <50% was 0.34 (HPD 95% CI [0.00,1.00]).

Secondary

Serum Creatinine at Baseline and Change From Baseline Over Time Post Transplant

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.

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

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline and up to 12 months

ID	Title	Description
OG000	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.

Units	Counts
Participants

Secondary

Urine Volume at Baseline and Change From Baseline Over Time Post Transplant

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.

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

Posted

Mean

Standard Deviation

Liter

Baseline (Pre-operative) and up to Day 28

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Number of Participants in the First 7 Days With: Primary Non Function, Functional DGF, Intermediate Graft Function, Immediate Graft Function

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.

All Subjects Population

Posted

Count of Participants

Participants

Up to Day 7

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Episodes of Biopsy-proven Acute Rejection

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.

All Subjects Population. Only those participants with data available at the specified time points were analyzed.

Posted

Count of Participants

Participants

Up to 12 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

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

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.

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

Posted

Mean

Standard Deviation

Picograms per milliliter

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Secondary

Number of Participants With Dialysis Events in the First 30 Days Post-transplant

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.

AP Population

Posted

Count of Participants

Participants

Up to 30 days

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Number of Participants Who Are Dialysis Independent at Visits up to 12 Months Post-transplant

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.

All Subjects Population

Posted

Count of Participants

Participants

Up to 12 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE)

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.

All Subjects Population

Posted

Count of Participants

Participants

Up to 12 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Number of Participants Having Any Abnormality in Hematology Results of Potential Clinical Importance

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).

All Subjects Population

Posted

Count of Participants

Participants

Up to 12 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

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).

All Subjects Population

Posted

Count of Participants

Participants

Up to 12 months

ID	Title	Description
OG000	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.

Secondary

Number of Participants Having Any Abnormality of Potential Clinical Importance of Vital Signs Results

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).

All Subjects Population

Posted

Count of Participants

Participants

Up to 12 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Number of Participants Having Infections

Number of participants having infections were summarized.

All Subjects Population

Posted

Count of Participants

Participants

Up to 12 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Serum Concentrations 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. PK Population included participants in the 'All Subjects' Population for whom a serum PK sample is obtained and analyzed for GSK1070806.

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

Posted

Mean

Standard Deviation

Nanograms per milliliter

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

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.

PK Population

Posted

Geometric Mean

95% Confidence Interval

Log (nanograms per milliliter)

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

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.

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

Posted

Geometric Mean

95% Confidence Interval

Log (Hour*nanograms per milliliter)

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

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.

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

Posted

Mean

Standard Deviation

Picograms per milliliter

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

ID	Title	Description
OG000	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.

Units	Counts
Participants

Secondary

Number of Participants With Positive Result in Anti-GSK1070806 Antibodies (ADAs)

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.

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.

Posted

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

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.

Posted

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Urinary tract infection	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0003 events1 affected7 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA 2.0	Systematic Assessment	EG0002 events1 affected7 at risk
Hernia	General disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Kidney transplant rejection	Immune system disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Transplant dysfunction	Injury, poisoning and procedural complications	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Ureteric obstruction	Renal and urinary disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Prostatomegaly	Reproductive system and breast disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Ureteral stent removal	Surgical and medical procedures	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Visceral leishmaniasis	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
End stage renal disease	Renal and urinary disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Cardiac failure	Cardiac disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 2.0	Systematic Assessment	EG0004 events4 affected7 at risk
Nausea	Gastrointestinal disorders	MedDRA 2.0	Systematic Assessment	EG0002 events2 affected7 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 2.0	Systematic Assessment	EG0002 events1 affected7 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 2.0	Systematic Assessment	EG0003 events3 affected7 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Frequent bowel movements	Gastrointestinal disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Lip swelling	Gastrointestinal disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Vomiting	Gastrointestinal disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 2.0	Systematic Assessment	EG0005 events5 affected7 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 2.0	Systematic Assessment	EG0002 events2 affected7 at risk
Urinary tract infection	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0004 events2 affected7 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Influenza	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0002 events1 affected7 at risk
Postoperative wound infection	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Urinary retention	Renal and urinary disorders	MedDRA 2.0	Systematic Assessment	EG0004 events2 affected7 at risk
Renal disorder	Renal and urinary disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Ureteric stenosis	Renal and urinary disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Blood creatine increased	Investigations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Blood potassium decreased	Investigations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Blood sodium decreased	Investigations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Body temperature decreased	Investigations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Candida test positive	Investigations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Haemoglobin increased	Investigations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Wound evisceration	Injury, poisoning and procedural complications	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Acidosis	Metabolism and nutrition disorders	MedDRA 2.0	Systematic Assessment	EG0002 events1 affected7 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 2.0	Systematic Assessment	EG0002 events1 affected7 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Hypertension	Vascular disorders	MedDRA 2.0	Systematic Assessment	EG0002 events2 affected7 at risk
Catheter site haemorrhage	General disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Kidney transplant rejection	Immune system disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Tremor	Nervous system disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Bacterial disease carrier	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Nail infection	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Pharyngotonsillitis	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Purulent discharge	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Urinary tract infection enterococcal	Infections and infestations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Blood glucose increased	Investigations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Cytomegalovirus test positive	Investigations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Weight increased	Investigations	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Renal impairment	Renal and urinary disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Arteriovenous fistula site complication	Injury, poisoning and procedural complications	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Post procedural discharge	Injury, poisoning and procedural complications	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Transplant rejection	Immune system disorders	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk
Product contamination	Product Issues	MedDRA 2.0	Systematic Assessment	EG0001 events1 affected7 at risk

ID	Term
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C000608195	GSK1070806
D009173	Mycophenolic Acid
D000305	Adrenal Cortex Hormones

ID	Term
D002208	Caproates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D005227	Fatty Acids
D008055	Lipids
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists