A Phase 2 interventional study of Belatacept in Renal Transplantation, sponsored by Bristol-Myers Squibb. Completed at 5 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-01-17.
Sponsored by Bristol-Myers Squibb · Phase 2, Interventional, and Treatment
The purpose of this study is to assess the pharmacokinetics and safety of belatacept in de novo renal transplant subjects treated with belatacept-based immunosuppressant medication
Bristol-Myers Squibb is the lead sponsor of 1,538 studies on the registry; 116 are open to participants now.
Of its 429 completed or terminated interventional studies of FDA-regulated products, 223 (52%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
10mg/kg 6 doses (Day 1, 5, week 2, 4, 8 and 12) for 12 weeks
Drug: Belatacept
5mg/kg 33 doses (every 4 weeks) for 144 weeks
Drug: Belatacept
IV infusion
Also known as: BMS-224818
Mean Belatacept Serum Concentrations Between Weeks 12 and 16 by Nominal Collection Time, Following 10mg/kg IV Belatacept - Pharmacokinetic Population
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.
Time frame: Day 84 to Day 112
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, 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.
Time frame: Day 84 to Day 112
Time of Maximum Observed Serum Concentration (Tmax) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population
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.
Time frame: Day 84 to Day 112
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
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 \[version 2.6.1\]). 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).
Time frame: Day 82 to Day 112
Total Body Clearance (CLT) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population
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).
Time frame: Day 84 to Day 112
Steady-state Volume Distribution (Vss) Following 10mg/kg IV Belatacept Between Weeks 12 and 16 - Pharmacokinetic Population
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. 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).
Time frame: Day 84 to Day 112
Serum Half Life (T-HALF) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population
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. 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).
Time frame: Day 84 to Day 112
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
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).
Time frame: Day 1 to Day 1092
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 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.
Time frame: Day 1 up to 4 years post transplantation
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Tryptophan - All Treated Participants
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)
Time frame: Baseline to Day 364
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Kynurenine - All Treated Participants
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).
Time frame: Day 1 to Day 364
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)
| Milestone | Belatacept 10mg/kg; 5mg/kg Maintenance |
|---|---|
| Started | 12 |
| Completed | 9 |
| Not completed | 3 |
| Withdrew: Death | 1 |
| Withdrew: Adverse event | 1 |
| Withdrew: Started marketed cellcept and prograf | 1 |
| Milestone | Belatacept 10mg/kg; 5mg/kg Maintenance |
|---|---|
| Started | 9 |
| Completed | 8 |
| Not completed | 1 |
| Withdrew: Adverse event | 1 |
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.
| ng/mL | Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance |
|---|---|
| 0.00 h | 8491.00 ± 5175.97 |
| 0.50 h | 242667 ± 64459.3 |
| 2.00 h | 212800 ± 62467.4 |
| 72.00 h | 55970.0 ± 12989.7 |
| 168.00 h | 36890.0 ± 16426.8 |
| 336.00 h | 19063.0 ± 7803.41 |
| 504.00 h | 11587.0 ± 6282.26 |
| 672 h | 7613.00 ± 4698.61 |
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.
| µg/mL | Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance |
|---|---|
| Cmin | 7.29 ± 61 |
| Cmax | 238.33 ± 27 |
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.
| hours | Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance |
|---|---|
| Time of Maximum Observed Serum Concentration (Tmax) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population | 0.60 (0.5 to 2.5) |
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 \[version 2.6.1\]). 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).
| µg*h/mL | Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance |
|---|---|
| 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 ± 35 |
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).
| µg/mL | 10mg/kg IV Belatacept |
|---|---|
| Day 5 Post Transplantation | 33.499 ± 25.020 |
| Day 14 Post Transplantation | 24.558 ± 40.605 |
| Day 28 Post Transplantation | 21.375 ± 39.224 |
| Day 56 Post Transplantation (N=12) | 8.574 ± 58.386 |
| Day 84 Post Transplantation | 7.289 ± 60.959 |
| Day 112 Post Transplantation | 6.391 ± 61.718 |
| Day 168 Post Transplantation | 3.189 ± 47.797 |
| Day 364 Post Transplantation | 3.704 ± 42.236 |
| Day 728 Post Transplantation | 4.383 ± 43.209 |
| Day 1092 Post Transplantation | 4.996 ± 55.892 |
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).
| mL/h/kg | Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance |
|---|---|
| Total Body Clearance (CLT) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population | 0.47 ± 27 |
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. 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).
| l/kg | Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance |
|---|---|
| Steady-state Volume Distribution (Vss) Following 10mg/kg IV Belatacept Between Weeks 12 and 16 - Pharmacokinetic Population | 0.11 ± 0.033 |
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. 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).
| hours | Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance |
|---|---|
| Serum Half Life (T-HALF) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population | 235.43 ± 76.414 |
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.
| participants | Belatacept 10mg/kg; 5mg/kg Maintenance |
|---|---|
| Acute rejection of transplant | 4 |
| Death | 1 |
| Graft Loss | 1 |
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)
| µM | Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance |
|---|---|
| Day 5 Post Transplantation | -27.375 ± 38.9151 |
| Day 28 Post Transplantation | -22.765 ± 39.0174 |
| Day 112 Post Transplantation | -27.331 ± 39.2819 |
| Day 168 Post Transplantation | -18.627 ± 37.9010 |
| Day 364 Post Transplantation | -24.610 ± 41.4859 |
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).
| µM | Belatacept 10mg/kg(3 Months); 5mg/kg Maintenance |
|---|---|
| Day 5 Post Transplantation | -7.276 ± 9.3070 |
| Day 28 Post Transplantation | -8.486 ± 9.1880 |
| Day 112 Post Transplantation | -7.936 ± 9.6630 |
| Day 168 Post Transplantation | -7.589 ± 9.6115 |
| Day 364 Post Transplantation | -7.279 ± 9.7117 |
Collected over 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.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Bela 10-5mg/kg | — | 6/12 (50%) | 12/12 (100%) |
| Event | Bela 10-5mg/kg |
|---|---|
| Urinary tract infectionInfections and infestations | 2/12 |
| MyelopathyNervous system disorders | 1/12 |
| NauseaGastrointestinal disorders | 1/12 |
| Benign prostatic hyperplasiaReproductive system and breast disorders | 1/12 |
| GastritisGastrointestinal disorders | 1/12 |
| Intracranial aneurysmNervous system disorders | 1/12 |
| PyrexiaGeneral disorders | 1/12 |
| Ureteral necrosisRenal and urinary disorders | 1/12 |
| Blood creatine increasedInvestigations | 1/12 |
| CellulitisInfections and infestations | 1/12 |
| Event | Bela 10-5mg/kg |
|---|---|
| Urinary tract infectionInfections and infestations | 7/12 |
| DyslipidaemiaMetabolism and nutrition disorders | 5/12 |
| Oedema peripheralGeneral disorders | 4/12 |
| AnaemiaBlood and lymphatic system disorders | 4/12 |
| Abdominal painGastrointestinal disorders | 4/12 |
| HypertensionVascular disorders | 4/12 |
| HeadacheNervous system disorders | 4/12 |
| DiarrhoeaGastrointestinal disorders | 4/12 |
| ConstipationGastrointestinal disorders | 4/12 |
| InfluenzaInfections and infestations | 4/12 |
Participants treated with study drug after renal transplant.
| Age, Categorical(Participants) | IV Belatacept 10mg/kg With 5mg/kg Maintenance |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 10 |
| >=65 years | 2 |
| Age, Continuous(years) | IV Belatacept 10mg/kg With 5mg/kg Maintenance |
|---|---|
| Mean | 48.7 ± 19.05 |
| Sex: Female, Male(Participants) | IV Belatacept 10mg/kg With 5mg/kg Maintenance |
|---|---|
| Female | 4 |
| Male | 8 |
| Region of Enrollment(participants) | IV Belatacept 10mg/kg With 5mg/kg Maintenance |
|---|---|
| United States | 4 |
| Mexico | 6 |
| Argentina | 2 |
| Weight(kilograms) | IV Belatacept 10mg/kg With 5mg/kg Maintenance |
|---|---|
| Mean | 74.90 ± 17.735 |
This study is completed, as verified in Dec 2013. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Bristol-Myers Squibb