Optimization of NULOJIX® Usage Towards Minimizing CNI Exposure in Simultaneous Pancreas and Kidney Transplantation

eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): * A score of ≥90 means kidney function is normal. * A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. * Scores between 30 and 59 indicates moderately reduced kidney function. * Scores between 15 and 29 indicate severely reduced kidney function. * Scores below 15 indicate very severe or end stage kidney failure.

Time frame: Week 52 Post-Transplant

Population: Intent-to-treat population with available data at week 52.

Viral infections following renal transplantation is a significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss. Specific viruses were monitored during this study using participant blood samples. Displayed are counts of participants who experienced BKV and CMV viremia as adverse events, diagnosed by test results from the local clinical pathology laboratory.

Time frame: Transplant through Week 52 Post-Transplant

Population: Intent-to-treat population

The stages of Chronic Kidney Disease are defined using the participant's GFR value: * Stage 1 if GFR value is ≥90 ( kidney function is normal) * Stage 2 if 60 ≤ GFR \< 90 (mildly reduced kidney function, pointing to kidney disease) * Stage 3A if 45 ≤ GFR \< 60\* * Stage 3B if 30 ≤ GFR \< 45\* * Stage 4 if 15 ≤ GFR \< 30 (severely reduced kidney function) * Stage 5 if GFR \< 15 (severe or end stage kidney failure). Stages 3A and 3B indicate moderately reduced kidney function.\*

Time frame: Week 52 Post-Transplant

Population: Intent-to-treat population

Viral infections following renal transplantation is a significant source of recipient morbidity and mortality, and a significant cause of allograft dysfunction and loss. Specific viruses were monitored during this study using participant blood samples. Displayed are counts of all participants diagnosed with EBV infection as an adverse event by EBV test(s), diagnosed by test results from the local clinical pathology laboratory.

Time frame: Transplant through Week 52 Post-Transplant

Population: Intent-to-treat population

An increased risk/incidence of malignancy is a recognized complication of immunosuppression in recipients of organ transplants. In Phase 3 clinical trials, overall malignancy rates were similar across all treatment groups, with the exception of posttransplant lymphoproliferative disease (PTLD).Displayed are counts of all participants who experienced malignancy reported as an adverse event.

Time frame: Transplant through Week 52 Post-Transplant

Population: Intent-to-treat population

Biopsy-proven acute rejection (AR) of the kidney (renal) or pancreas during the first 52 weeks post-transplant. AR grading using standard Banff\* criteria. For both kidney and pancreas, AR is defined as a grade ≥1. * AR for the kidney: Banff 2007 criteria. Severity of AR is graded by as IA, IB, IIA, IIB, or III, with IA defined as the mildest form of AR and III being the most severe. * AR for the pancreas: Banff 2011 Criteria. Severity of AR is graded as I, II, or III, with I defined as the mildest form of AR and III being the most severe.

Time frame: Transplant through Week 52

Population: Intent-to-treat population

Infections were required to be reported as a serious adverse event if they required either inpatient hospitalization or prolongation of a current hospitalization. Displayed are counts of all participants who experienced infection(s) as an adverse event, by treatment group.

Time frame: Transplant through Week 52 Post-Transplant

Population: Intent-to-treat population

Humoral rejection (i.e., antibody mediated rejection) of: 1. the kidney as defined by diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury determined by local pathology and, 2. the pancreas as defined by the presence of circulating anti-donor antibodies, and histopathological data including morphologic evidence of microvascular tissue injury and C4d staining in interacinar capillaries determined by local pathology.

Time frame: Transplant through Week 52

Population: Intent-to-treat population with available data

The stages of Chronic Kidney Disease (CKD) are defined using the participant's GFR value: * Stage 1 if GFR value is ≥ 90 (kidney function is normal) * Stage 2 if 60 ≤ GFR \< 90 (mildly reduced kidney function, pointing to kidney disease) * Stage 3A if 45 \<= GFR \< 60\* * Stage 3B if 30 \<= GFR \< 45\* * Stage 4 if 15 ≤ GFR \< 30 (severely reduced kidney function) * Stage 5 if GFR \< 15 (severe or end stage kidney failure). Stages 3A abd 3B indicate moderately reduced kidney function.\*

Time frame: Week 52 Post-Transplant

Population: Intent-to-treat population

Delayed grafted function is defined as dialysis in the first week on one or more occasions for any indication other than the treatment of acute hyperkalemia in the setting of otherwise acceptable renal function.

Time frame: Transplant through Week 52 Post-Transplant

Population: Intent-to-treat population

The de novo development of donor-specific antibody (DSA) is associated with an increased risk of graft rejection. The presence of anti-Histocompatibility Antigen (HLA) antibodies (alloantibodies) is associated with increased risk of acute and chronic injury to the transplant allograft.

Time frame: Transplant through Week 52

Population: Intent-to-treat population with available data

eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): * A score of ≥90 means kidney function is normal. * A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. * Scores between 30 and 59 indicates moderately reduced kidney function. * Scores between 15 and 29 indicate severely reduced kidney function. * Scores below 15 indicate very severe or end stage kidney failure.

Time frame: Week 52 Post-Transplant

Population: Intent-to-treat population

This measure counts death, graft loss, or undetectable C-peptide value (e.g., C-peptide \<0.3 ng/mL) occurring at any point post-transplant and independent of each other. * Kidney Graft Loss was defined as 90 consecutive days of dialysis dependency. * Pancreas graft loss was defined as returning to exogenous insulin therapy or initiation of oral hypoglycemic agents for greater than 30 days. * Factitious hypoglycemia due to surreptitious insulin administration results in elevated serum insulin levels and low or undetectable C-peptide levels.

Time frame: Transplant through Week 52 Post-Transplant

Population: Intent-to-treat population with available data.

C-peptide is a measure of pancreatic function. The definition of pancreatic loss: a C-peptide value of \<0.3 ng/mL.

Time frame: Week 52 Post-Transplant

Population: Intent-to-treat population with available data

C-peptide is a measure of pancreatic function. The definition of partial pancreatic graft function: a fasting C-peptide levels \>0.3ng.mL (0.1nmol.L) plus the participant's continued requirement for exogenous insulin or oral hypoglycemic agent(s).

Time frame: Week 52 Post-Transplant

Population: Intent-to-treat population with available data

Participants with full pancreatic graft functions are defined as those that no longer require exogenous insulin therapy.

Time frame: Week 52 Post-Transplant

Population: Intent-to-treat population

Participants achieved successful discontinuation if they were able to discontinue (e.g., off tacrolimus therapy completely) over a 4-8 weeks after tacrolimus withdrawal was initiated at week 40.

Time frame: Week 40 through week 48 Post-Transplant

Population: Intent-to-treat population with available data

Adverse events were collected systematically. Counts of all participants who experienced at least one adverse event (AEs, SAEs) by assigned treatment group. Refer to the Serious Adverse Events and Other Adverse Events tables for more detail.

Time frame: From Enrollment (Pre-Transplant) to Week 52 Post-Transplant

Population: Intent-to-treat population

Anti-hypertensive medications are a class of drugs that are used to treat hypertension. The medications seek to prevent the complications of high blood pressure, such as stoke and myocardial infarction.

Time frame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52

Population: Intent-to-treat population with available data

Lipid lowering medications are used in the treatment of high levels of fats (lipids), such as cholesterol in blood

Time frame: Baseline (Pre-Transplant), Week 28, and Week 52

Population: Intent-to-treat population

Fasting blood sugar (e.g., glucose) test is used to help diagnose diabetes, prediabetes, and gestational diabetes. Reference fasting blood sugar (glucose) values: * 70 to 99 mg/dL is normal * 100 to 125 mg/dL is considered prediabetes * 126 mg/dL or higher on two separate tests is considered diabetes.

Time frame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52

Population: Intent-to-treat population with available data

A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: * Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease * LDL cholesterol: \<70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; \<100 mg/dL for people considered high risk for cardiovascular disease; \<130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease * HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease * Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and * Triglycerides: \<150 mg/dL; high values indicate risk of cardiovascular disease.

Time frame: Baseline (Pre-Transplant)

Population: Intent-to-treat population with available data

A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: * Total cholesterol: 75-169 mg/dL if age ≤20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease * LDL cholesterol: \<70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; \<100 mg/dL for people considered high risk for cardiovascular disease; \<130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease * HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease * Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and * Triglycerides: \<150 mg/dL; high values indicate risk of cardiovascular disease.

Time frame: Week 28 Post-Transplant

Population: Intent-to-treat population with available data

Hemoglobin A1c (HbA1c) measures the average blood glucose levels over 8-12 weeks, thus acting as a useful long-term gauge of blood glucose control: * A value below 6.0% reflects normal levels, * 6.0% to 6.4% reflects prediabetes, and * a value of ≥ 6.5% reflects diabetes.

Time frame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52

Population: Intent-to-treat population with available data

A fasting lipid profiles measures total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. These measurements are used in assessing one's risk of cardiovascular disease. Target ranges for each of these measures are provided: * Total cholesterol: 75-169 mg/dL if age ≤ 20; 100-199 mg/dL if age ≥ 21; high values indicate risk of cardiovascular disease * LDL cholesterol: \<70 mg/dL for people with documented cardiovascular disease or metabolic syndrome; \<100 mg/dL for people considered high risk for cardiovascular disease; \<130 mg/dL for people considered low risk for cardiovascular disease; high values indicate risk of cardiovascular disease * HDL cholesterol: 40mg/dL and higher; high values indicate reduced risk of cardiovascular disease * Non-HDL cholesterol: 30 mg/dL above the target value for LDL cholesterol; high values indicate risk of cardiovascular disease and * Triglycerides: \<150 mg/dL; high values indicate risk of cardiovascular disease.

Time frame: Week 52 Post-Transplant

Population: Intent-to-treat population with available data

The estimated Glomerular Filtration Rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation (MDRD): * A score of ≥ 90 means kidney function is normal. * A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. * Scores between 30 and 59 indicates moderately reduced kidney function. * Scores between 15 and 29 indicate severely reduced kidney function. * Scores below 15 indicate severe or endstage kidney failure.

Time frame: Week 52 Post-Transplant

Population: Intent-to-treat population

AR grading using standard Banff\* criteria. For both kidney and pancreas, AR is defined as a grade ≥1. * AR for the kidney: Banff 2007 criteria. Severity of AR is graded by as IA, IB, IIA, IIB, or III, with IA defined as the mildest form of AR and III being the most severe. * AR for the pancreas: Banff 2011 Criteria. Severity of AR is graded is I, II, or III, with I defined as the mildest form of AR and III being the most severe.

Time frame: Transplant through Week 52

Population: Intent-to-treat population

A blood pressure measurement consists of two numbers: the systolic and diastolic pressures. Systolic pressure measures the pressure in blood vessels when the heart beats. Diastolic pressure measures the pressure in blood vessels between beats of the heart. * Systolic measures of \<120 and diastolic measures of \<80 are considered normal. * Systolic measures of 120-139 and diastolic measures of 80-89 are considered at risk (or pre-hypertension). * Systolic measures of ≥140 and diastolic measures of ≥90 are considered high.

Time frame: Baseline (Pre-Transplant) and Days 28, 84, and Weeks 28, 36, and 52

Population: Intent-to-treat population with available data

The estimated Glomerular Filtration Rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI): * A score of ≥ 90 means kidney function is normal. * A score between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. * Scores between 30 and 59 indicates moderately reduced kidney function. * Scores between 15 and 29 indicate severely reduced kidney function. * Scores below 15 indicate very severe or endstage kidney failure. An estimate of the slope, or change over time, in eGFR was produced using standard statistical linear modeling procedures. The estimate was then re-scaled so that it could be interpreted as a change in eGFR per month. Positive numbers indicate increasing kidney function. Larger numbers indicate greater change in kidney function.

Time frame: Day 28 through Week 52 Post-Transplant

Population: Intent-to-treat population

Participants are stratified by kidney biopsy results/treatment received. Upon having a for-cause biopsy performed, persons often receive treatment for rejection based on the biopsy results, which may or may not reveal signs of rejection. Details of biopsy findings and corresponding treatment are provided for each instance of treatment for rejection. Results summary format: biopsy results; treatment. Acronyms and abbreviations: * ACR=Acute Cellular Rejection * IFTA=Interstitial Fibrosis and Tubular Atrophy * ATG=Anti-thymocyte globulin therapy * IVIG=Intravenous Immunoglobulin therapy * Gd =Grade * PO=Orally * QD=Daily

Time frame: Transplant through Week 52

Population: Intent-to-treat population with available data. Only 'for cause' biopsies were performed post-transplant.

Participants are stratified by kidney biopsy results/treatment received. In the event of a for cause renal (kidney) biopsy: -The diagnosis of acute cellular rejection (ACR) using the Banff 2007 renal allograft pathology criteria. These criteria for renal allograft biopsies is an international histopathological classification standard. ACR is defined by a renal biopsy demonstrating a Banff 2007 classification of Grade IA or greater, with higher scores indicating more severe rejection. (Ref: Solez K, Colvin RB et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008 8(4): 753-60). Acronyms and abbreviations: * ACR=Acute Cellular Rejection\* * Normal\* * Borderline\* (criteria for ACR not fulfilled) * Gd.=Grade\* * IFTA=Interstitial Fibrosis and Tubular Atrophy\* * ATG=Anti-thymocyte globulin therapy * IVIG=Intravenous Immunoglobulin therapy * PO=Orally * QD=Daily \*Banff 2007 renal allograft pathology criteria

Time frame: Transplant through Week 52

Population: Intent-to-treat population with available data. All participants were considered evaluable for rejection. Only 'for cause' biopsies were performed post-transplant.