Trial Outcomes & Findings for Belatacept Pharmacokinetic Trial in Renal Transplantation (NCT NCT00578448)
NCT ID: NCT00578448
Last Updated: 2014-01-17
Results Overview
Pharmacokinetic (PK) sampling started from pre-dose (0 hour) on Day 84 and ended at 672 hour (h) on Day 112 (between Weeks 12 to 16). The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method and measured as nanograms/milliliter (ng/mL). Less than the lower limit of quantification (LLQ), 3.000 ng/mL concentration value was treated as missing.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
14 participants
Primary outcome timeframe
Day 84 to Day 112
Results posted on
2014-01-17
Participant Flow
First participant, first visit: 3 March 2008. Last subject, last visit 6 September 2012. Participants had received a renal transplant from a living or deceased donor with an anticipated cold ischemia time of less than (\<) 24 hours (h)
14 participants enrolled; 12 received study drug; 2 not treated due to: kidney damage (1) and prolonged cold ischemia (1). Study continued for up to 3 years until drug approval in participant's country. Participants continued in a 1 year extension after conclusion of the 3rd year.
Participant milestones
| Measure |
Belatacept 10mg/kg; 5mg/kg Maintenance
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 4 (Weeks 8 and 12). After 4 months, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the trial (3 years and then a 1 year extension was available for those who completed the 3rd year).
|
|---|---|
|
Day 1 up to 3 Years of Planned Study
STARTED
|
12
|
|
Day 1 up to 3 Years of Planned Study
COMPLETED
|
9
|
|
Day 1 up to 3 Years of Planned Study
NOT COMPLETED
|
3
|
|
1 Year Long Term Extension (LTE)
STARTED
|
9
|
|
1 Year Long Term Extension (LTE)
COMPLETED
|
8
|
|
1 Year Long Term Extension (LTE)
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Belatacept 10mg/kg; 5mg/kg Maintenance
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 4 (Weeks 8 and 12). After 4 months, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the trial (3 years and then a 1 year extension was available for those who completed the 3rd year).
|
|---|---|
|
Day 1 up to 3 Years of Planned Study
Death
|
1
|
|
Day 1 up to 3 Years of Planned Study
Adverse Event
|
1
|
|
Day 1 up to 3 Years of Planned Study
started marketed Cellcept and Prograf
|
1
|
|
1 Year Long Term Extension (LTE)
Adverse Event
|
1
|
Baseline Characteristics
Belatacept Pharmacokinetic Trial in Renal Transplantation
Baseline characteristics by cohort
| Measure |
IV Belatacept 10mg/kg With 5mg/kg Maintenance
n=12 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 4 (Weeks 8 and 12). After 4 months, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the trial.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
|
Age, Continuous
|
48.7 years
STANDARD_DEVIATION 19.05 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
2 participants
n=5 Participants
|
|
Weight
|
74.90 kilograms
STANDARD_DEVIATION 17.735 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 84 to Day 112Population: Number (N) of participants analyzed for each collection time was 10, except for time 0.50 h, which was missing 1 participant. Therefore Number (N) for Time 0.50 h = 9.
Pharmacokinetic (PK) sampling started from pre-dose (0 hour) on Day 84 and ended at 672 hour (h) on Day 112 (between Weeks 12 to 16). The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method and measured as nanograms/milliliter (ng/mL). Less than the lower limit of quantification (LLQ), 3.000 ng/mL concentration value was treated as missing.
Outcome measures
| Measure |
Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance
n=10 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 3. After Day 112, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the study.
|
|---|---|
|
Mean Belatacept Serum Concentrations Between Weeks 12 and 16 by Nominal Collection Time, Following 10mg/kg IV Belatacept - Pharmacokinetic Population
0.00 h
|
8491.00 ng/mL
Standard Deviation 5175.97
|
|
Mean Belatacept Serum Concentrations Between Weeks 12 and 16 by Nominal Collection Time, Following 10mg/kg IV Belatacept - Pharmacokinetic Population
0.50 h
|
242667 ng/mL
Standard Deviation 64459.3
|
|
Mean Belatacept Serum Concentrations Between Weeks 12 and 16 by Nominal Collection Time, Following 10mg/kg IV Belatacept - Pharmacokinetic Population
2.00 h
|
212800 ng/mL
Standard Deviation 62467.4
|
|
Mean Belatacept Serum Concentrations Between Weeks 12 and 16 by Nominal Collection Time, Following 10mg/kg IV Belatacept - Pharmacokinetic Population
72.00 h
|
55970.0 ng/mL
Standard Deviation 12989.7
|
|
Mean Belatacept Serum Concentrations Between Weeks 12 and 16 by Nominal Collection Time, Following 10mg/kg IV Belatacept - Pharmacokinetic Population
168.00 h
|
36890.0 ng/mL
Standard Deviation 16426.8
|
|
Mean Belatacept Serum Concentrations Between Weeks 12 and 16 by Nominal Collection Time, Following 10mg/kg IV Belatacept - Pharmacokinetic Population
336.00 h
|
19063.0 ng/mL
Standard Deviation 7803.41
|
|
Mean Belatacept Serum Concentrations Between Weeks 12 and 16 by Nominal Collection Time, Following 10mg/kg IV Belatacept - Pharmacokinetic Population
504.00 h
|
11587.0 ng/mL
Standard Deviation 6282.26
|
|
Mean Belatacept Serum Concentrations Between Weeks 12 and 16 by Nominal Collection Time, Following 10mg/kg IV Belatacept - Pharmacokinetic Population
672 h
|
7613.00 ng/mL
Standard Deviation 4698.61
|
PRIMARY outcome
Timeframe: Day 84 to Day 112Population: One participant excluded from analysis of Cmax and Tmax due to a very high concentration value (it was considered an outlier) therefore, for Cmax, Number of participants analyzed (N)=9.
Cmax, Cmin are measured in micrograms per milliliter (µg/mL). At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 hour (h) on Day 112. Serum samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). Actual sampling times were used for PK calculations. The Cmax, and the Cmin were recorded directly from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria, which is also referred to as adjusted R-squared. Values below lower limits of quantification (LLQ), 0.003 µg/mL, were set to 0.0015 for computation of summary statistics.
Outcome measures
| Measure |
Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance
n=10 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 3. After Day 112, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the study.
|
|---|---|
|
Maximum Observed Serum Concentration (Cmax) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept and Trough Serum Concentration Prior to Dosing (Cmin) - Pharmacokinetic Population
Cmin
|
7.29 µg/mL
Geometric Coefficient of Variation 61
|
|
Maximum Observed Serum Concentration (Cmax) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept and Trough Serum Concentration Prior to Dosing (Cmin) - Pharmacokinetic Population
Cmax
|
238.33 µg/mL
Geometric Coefficient of Variation 27
|
PRIMARY outcome
Timeframe: Day 84 to Day 112Population: 1 participant excluded from analysis of Cmax and Tmax due to a very high concentration value (it was considered an outlier) therefore, for Tmax, Number of participants analyzed (N)=9.
Tmax measured in hours (h). At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 (h) on Day 112 . The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). Actual sampling times were used for PK calculations.
Outcome measures
| Measure |
Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance
n=9 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 3. After Day 112, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the study.
|
|---|---|
|
Time of Maximum Observed Serum Concentration (Tmax) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population
|
0.60 hours
Interval 0.5 to 2.5
|
PRIMARY outcome
Timeframe: Day 82 to Day 112At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 hour (h) on Day 112. The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). The area under the concentration-time curve in one dose interval \[AUC(TAU), where TAU = 4 weeks\] were calculated using the mixed log-linear trapezoidal algorithm in Kinetica. Actual sampling times were used for PK calculations. AUC (TAU) was measured as micrograms multiplied by time(h) per milliliter (µg\*h/mL).
Outcome measures
| Measure |
Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance
n=10 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 3. After Day 112, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the study.
|
|---|---|
|
Area Under the Concentration Time Curve Within a Dosing Interval (AUC) (TAU) Between Weeks 12 and 16 Following 10 mg/kg IV Belatacept - Pharmacokinetic Population
|
21241 µg*h/mL
Geometric Coefficient of Variation 35
|
PRIMARY outcome
Timeframe: Day 84 to Day 112Population: Participants who were treated and had PK data.
At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 hour (h) on Day 112. The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). Actual sampling times were used for PK calculations. CLT was calculated by dividing the dose by AUC(TAU) and was adjusted to body weight. CLT was measured as milliliter per time per kg body weight (mL/h/kg).
Outcome measures
| Measure |
Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance
n=10 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 3. After Day 112, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the study.
|
|---|---|
|
Total Body Clearance (CLT) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population
|
0.47 mL/h/kg
Geometric Coefficient of Variation 27
|
PRIMARY outcome
Timeframe: Day 84 to Day 112At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 hour (h) on Day 112. The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). Actual sampling times were used for PK calculations. Vss was calculated by dividing the dose by AUC and multiply the mean residence time (MRT). Vss was adjusted to body weight and measured as liter per kilogram body weight (l/kg).
Outcome measures
| Measure |
Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance
n=10 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 3. After Day 112, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the study.
|
|---|---|
|
Steady-state Volume Distribution (Vss) Following 10mg/kg IV Belatacept Between Weeks 12 and 16 - Pharmacokinetic Population
|
0.11 l/kg
Standard Deviation 0.033
|
PRIMARY outcome
Timeframe: Day 84 to Day 112At Day 84, blood samples obtained from pre-dose (0 hour) and ended at 672 hour (h) on Day 112. The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). Actual sampling times were used for PK calculations. T-HALF was calculated as ln2/Lz, where Lz is the absolute value of the slope of the terminal log-linear phase. T-HALF is measured in hours (h).
Outcome measures
| Measure |
Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance
n=10 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 3. After Day 112, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the study.
|
|---|---|
|
Serum Half Life (T-HALF) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population
|
235.43 hours
Standard Deviation 76.414
|
SECONDARY outcome
Timeframe: Day 1 to Day 1092Population: Number of participants (N) analyzed = 11 for Days 5, 14,and 28; and 12 for Day 56. Days 84, 112, 168, 364 N=10.
Blood samples were obtained pre and post dose at designated time points up to Day 112 and thereafter, pre-dose samples were obtained at Days 168 and 364, and then once yearly up to end of Year 3. The samples were analyzed for belatacept by enzyme-linked immunosorbent assay (ELISA) using a validated method. Individual participant PK parameters were derived from serum concentration versus time data using a non-compartmental method, using a validated PK analysis program (KineticaTM 4.4.1 within the eToolbox \[version 2.6.1\]). Actual sampling times were used for PK calculations. The trough serum concentration (Cmin), was recorded directly from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria, which is also referred to as adjusted R-squared. Cmin was measured as micrograms per milliliter (µg/mL).
Outcome measures
| Measure |
Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance
n=11 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 3. After Day 112, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the study.
|
|---|---|
|
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
Day 14 Post Transplantation
|
24.558 µg/mL
Geometric Coefficient of Variation 40.605
|
|
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
Day 5 Post Transplantation
|
33.499 µg/mL
Geometric Coefficient of Variation 25.020
|
|
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
Day 28 Post Transplantation
|
21.375 µg/mL
Geometric Coefficient of Variation 39.224
|
|
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
Day 56 Post Transplantation (N=12)
|
8.574 µg/mL
Geometric Coefficient of Variation 58.386
|
|
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
Day 84 Post Transplantation
|
7.289 µg/mL
Geometric Coefficient of Variation 60.959
|
|
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
Day 112 Post Transplantation
|
6.391 µg/mL
Geometric Coefficient of Variation 61.718
|
|
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
Day 168 Post Transplantation
|
3.189 µg/mL
Geometric Coefficient of Variation 47.797
|
|
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
Day 364 Post Transplantation
|
3.704 µg/mL
Geometric Coefficient of Variation 42.236
|
|
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
Day 728 Post Transplantation
|
4.383 µg/mL
Geometric Coefficient of Variation 43.209
|
|
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
Day 1092 Post Transplantation
|
4.996 µg/mL
Geometric Coefficient of Variation 55.892
|
SECONDARY outcome
Timeframe: Day 1 up to 4 years post transplantationPopulation: All treated participants were analyzed during the planned 3 year study N=12. Only 9 participants entered the LTE so N=9 for LTE.
Acute rejection of transplant defined as a clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. Graft loss was defined as either functional loss or physical loss. Day 1 is day of transplantation.
Outcome measures
| Measure |
Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance
n=12 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 3. After Day 112, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the study.
|
|---|---|
|
Acute Rejection, Graft Loss, and Death up to 3 Years Post Transplantation in Planned Study and 1 Year Long Term Extension - All Treated Participants
Acute rejection of transplant
|
4 participants
|
|
Acute Rejection, Graft Loss, and Death up to 3 Years Post Transplantation in Planned Study and 1 Year Long Term Extension - All Treated Participants
Death
|
1 participants
|
|
Acute Rejection, Graft Loss, and Death up to 3 Years Post Transplantation in Planned Study and 1 Year Long Term Extension - All Treated Participants
Graft Loss
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline to Day 364Population: Number analyzed for Baseline, Days 5, 28, 112, 168, 364 = 12, 11, 11, 10, 10, and 10, respectively.
Indoleamine 2,3 dioxygenase (IDO) is a tryptophan catabolizing enzyme that can be induced in antigen-presenting cells by the engagement of B7 by cytotoxic lymphocyte antigen 4 (CTLA-4). Tryptophan depletion in cellular microenvironments has an inhibitory effect on T cells and may be part of a broader immuno-regulatory effect of IDO induction. The IDO activity was determined by measuring the quantity of tryptophan and its metabolite, kynurenine, in serum samples using a validated high performance liquid chromatography (HPLC) method. Baseline is defined as pre-dose. Tryptophan was measured in micromoles (µM)
Outcome measures
| Measure |
Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance
n=12 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 3. After Day 112, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the study.
|
|---|---|
|
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Tryptophan - All Treated Participants
Day 5 Post Transplantation
|
-27.375 µM
Standard Deviation 38.9151
|
|
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Tryptophan - All Treated Participants
Day 28 Post Transplantation
|
-22.765 µM
Standard Deviation 39.0174
|
|
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Tryptophan - All Treated Participants
Day 112 Post Transplantation
|
-27.331 µM
Standard Deviation 39.2819
|
|
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Tryptophan - All Treated Participants
Day 168 Post Transplantation
|
-18.627 µM
Standard Deviation 37.9010
|
|
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Tryptophan - All Treated Participants
Day 364 Post Transplantation
|
-24.610 µM
Standard Deviation 41.4859
|
SECONDARY outcome
Timeframe: Day 1 to Day 364Population: Number analyzed for Baseline, Days 5, 28, 112, 168, 364 = 12, 11, 11, 10, 10, and 10, respectively.
Indoleamine 2,3 dioxygenase (IDO) is a tryptophan catabolizing enzyme that can be induced in antigen-presenting cells by the engagement of B7 by CTLA-4. Tryptophan depletion in cellular microenvironments has an inhibitory effect on T cells and may be part of a broader immuno-regulatory effect of IDO induction. The IDO activity was determined by measuring the quantity of tryptophan and its metabolite, kynurenine, in serum samples using a validated high performance liquid chromatography (HPLC) method. Baseline is defined as pre-dose. Kynurenine was measured in micromoles (µM).
Outcome measures
| Measure |
Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance
n=12 Participants
Participants received intravenous (IV) belatacept (10 milligram per kilogram body weight (mg/kg) on Days 1 and 5, and then every 2 weeks through Month 1 (Weeks 2 and 4), and then every 4 weeks through Month 3. After Day 112, participants received a maintenance dose of 5 mg/kg belatacept administered every 4 weeks until completion of the study.
|
|---|---|
|
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Kynurenine - All Treated Participants
Day 112 Post Transplantation
|
-7.936 µM
Standard Deviation 9.6630
|
|
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Kynurenine - All Treated Participants
Day 5 Post Transplantation
|
-7.276 µM
Standard Deviation 9.3070
|
|
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Kynurenine - All Treated Participants
Day 28 Post Transplantation
|
-8.486 µM
Standard Deviation 9.1880
|
|
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Kynurenine - All Treated Participants
Day 168 Post Transplantation
|
-7.589 µM
Standard Deviation 9.6115
|
|
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Kynurenine - All Treated Participants
Day 364 Post Transplantation
|
-7.279 µM
Standard Deviation 9.7117
|
Adverse Events
Bela 10-5mg/kg
Serious events: 6 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bela 10-5mg/kg
n=12 participants at risk
|
|---|---|
|
Nervous system disorders
Myelopathy
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Gastritis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Nervous system disorders
Intracranial aneurysm
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
General disorders
Pyrexia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Renal and urinary disorders
Ureteral necrosis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Investigations
Blood creatine increased
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Cellulitis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Dehydration
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Meningitis viral
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Urinary tract infection
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Septic shock
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Congenital, familial and genetic disorders
Congenital cystic kidney disease
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Gastritis haemorrhagic
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Pneumonia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Retroperitoneal haematoma
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
Other adverse events
| Measure |
Bela 10-5mg/kg
n=12 participants at risk
|
|---|---|
|
Reproductive system and breast disorders
Genital lesion
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Nervous system disorders
Headache
|
33.3%
4/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Vascular disorders
Aneurysm
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Cardiac disorders
Arrhythmia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
General disorders
Chest pain
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Injury, poisoning and procedural complications
Contusion
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Eye disorders
Eye pain
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Injury, poisoning and procedural complications
Foot fracture
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
25.0%
3/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Endocrine disorders
Hypothyroidism
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Psychiatric disorders
Insomnia
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Nervous system disorders
Myelopathy
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
General disorders
Oedema peripheral
|
33.3%
4/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Onychomycosis
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Pharyngotonsillitis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Pyelonephritis acute
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Respiratory tract infection
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Injury, poisoning and procedural complications
Skin injury
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Abdominal distension
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Blood and lymphatic system disorders
Anaemia
|
33.3%
4/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Investigations
Blood creatine phosphokinase increased
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Colitis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Eye disorders
Eye haemorrhage
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Food poisoning
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Gastritis
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Herpes zoster
|
25.0%
3/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Renal and urinary disorders
Hydronephrosis
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
General disorders
Malaise
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Nervous system disorders
Neuropathy peripheral
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Oral candidiasis
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Pharyngitis
|
25.0%
3/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Tinea versicolour
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Ear and labyrinth disorders
Vertigo
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
4/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Vascular disorders
Arterial spasm
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Candidiasis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Eye disorders
Chalazion
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Glucose tolerance impaired
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Haematochezia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Herpes simplex
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Vascular disorders
Hypertension
|
33.3%
4/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
General disorders
Influenza like illness
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Molluscum contagiosum
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Mouth ulceration
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
General disorders
Pyrexia
|
25.0%
3/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Musculoskeletal and connective tissue disorders
Scoliosis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Cardiac disorders
Tachycardia
|
25.0%
3/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Injury, poisoning and procedural complications
Traumatic renal injury
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
BK virus infection
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
General disorders
Chills
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
General disorders
Fatigue
|
25.0%
3/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Flatulence
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Fluid overload
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Gastrointestinal sounds abnormal
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Injury, poisoning and procedural complications
Graft dysfunction
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
25.0%
3/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Hypocholesterolaemia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Injury, poisoning and procedural complications
Incision site pain
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Infected cyst
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Nasopharyngitis
|
25.0%
3/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Overweight
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Renal and urinary disorders
Perinephric effusion
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Postoperative wound infection
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Renal and urinary disorders
Proteinuria
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Renal and urinary disorders
Renal vein thrombosis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Staphylococcal infection
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Investigations
White blood cell count decreased
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Injury, poisoning and procedural complications
Wound evisceration
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Skin and subcutaneous tissue disorders
Acne
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Body tinea
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Cellulitis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Nervous system disorders
Cerebral infarction
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Nervous system disorders
Cervicobrachial syndrome
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
General disorders
Cyst
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Dehydration
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Reproductive system and breast disorders
Genital discharge
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Nervous system disorders
Hypoaesthesia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Renal and urinary disorders
Leukocyturia
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Investigations
Liver function test abnormal
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Blood and lymphatic system disorders
Polycythaemia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Renal and urinary disorders
Renal haemorrhage
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Sinusitis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Urinary tract infection
|
58.3%
7/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Nervous system disorders
Amnesia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Investigations
Body temperature increased
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
41.7%
5/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Dyspepsia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Renal and urinary disorders
Dysuria
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Folliculitis
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Gastroenteritis
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
25.0%
3/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
General disorders
Oedema
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Nervous system disorders
Paraesthesia
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Eye disorders
Retinal haemorrhage
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Renal and urinary disorders
Urethral stenosis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Investigations
Blood creatinine increased
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Psychiatric disorders
Depression
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
4/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Dry mouth
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Vascular disorders
Hypotension
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Incision site cellulitis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Blood and lymphatic system disorders
Leukopenia
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Odynophagia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Skin and subcutaneous tissue disorders
Papule
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Renal and urinary disorders
Urinary retention
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Abdominal pain lower
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Psychiatric disorders
Anxiety
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Constipation
|
33.3%
4/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Nervous system disorders
Dizziness
|
25.0%
3/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Furuncle
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Hiatus hernia
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Influenza
|
33.3%
4/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
General disorders
Ischaemic ulcer
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Renal and urinary disorders
Nocturia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Gastrointestinal disorders
Oesophagitis
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Musculoskeletal and connective tissue disorders
Osteopenia
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Cardiac disorders
Palpitations
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Tinea cruris
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Investigations
Troponin increased
|
16.7%
2/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Upper respiratory tract infection
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Investigations
Urine output increased
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
|
Infections and infestations
Vaginal infection
|
8.3%
1/12 • Day 1 (day of transplant) up to 3 years post transplant for the study and 1 additional year for the 1 year extension for those participants who entered the extension.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER