- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00578448
Belatacept Pharmacokinetic Trial in Renal Transplantation
December 16, 2013 updated by: Bristol-Myers Squibb
An Open-label Pharmacokinetic Study in De Novo Renal Transplant Subjects Receiving a Belatacept Based Immunosuppressant Regimen
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
Study Overview
Study Type
Interventional
Enrollment (Actual)
14
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Buenos Aires
-
Capital Federal, Buenos Aires, Argentina, 1425
- Local Institution
-
-
-
-
-
Aguascalientes, Mexico, 20219
- Local Institution
-
-
Morelos
-
Cuernavaca, Morelos, Mexico, 62448
- Local Institution
-
-
-
-
Massachusetts
-
Springfield, Massachusetts, United States, 01107
- Western New England Renal & Transplant
-
-
Michigan
-
Detriot, Michigan, United States, 48202
- Henry Ford Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Recipient of a living or deceased donor kidney
- First or second transplant
- Men and women, including women of childbearing potential, 18 years and older
Exclusion Criteria:
- Panel reactive antibodies ≥ 30%
- Significant infection
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: A
10mg/kg 6 doses (Day 1, 5, week 2, 4, 8 and 12) for 12 weeks |
IV infusion
Other Names:
|
Active Comparator: B
5mg/kg 33 doses (every 4 weeks) for 144 weeks |
IV infusion
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Belatacept Serum Concentrations Between Weeks 12 and 16 by Nominal Collection Time, Following 10mg/kg IV Belatacept - Pharmacokinetic Population
Time Frame: Day 84 to Day 112
|
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.
|
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
Time Frame: Day 84 to Day 112
|
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.
|
Day 84 to Day 112
|
Time of Maximum Observed Serum Concentration (Tmax) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population
Time Frame: Day 84 to Day 112
|
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.
|
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
Time Frame: Day 82 to Day 112
|
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).
|
Day 82 to Day 112
|
Total Body Clearance (CLT) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population
Time Frame: Day 84 to Day 112
|
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).
|
Day 84 to Day 112
|
Steady-state Volume Distribution (Vss) Following 10mg/kg IV Belatacept Between Weeks 12 and 16 - Pharmacokinetic Population
Time Frame: Day 84 to Day 112
|
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).
|
Day 84 to Day 112
|
Serum Half Life (T-HALF) Between Weeks 12 and 16 Following 10mg/kg IV Belatacept - Pharmacokinetic Population
Time Frame: Day 84 to Day 112
|
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).
|
Day 84 to Day 112
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Summary of Trough Serum Concentration of Belatacept Prior to Dosing up to 3 Years Post Transplantation - Pharmacokinetic Population
Time Frame: Day 1 to Day 1092
|
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).
|
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
Time Frame: Day 1 up to 4 years post transplantation
|
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.
|
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
Time Frame: Baseline to Day 364
|
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)
|
Baseline to Day 364
|
Mean Change From Baseline to Days 5, 28, 112, 168, and 364 in Kynurenine - All Treated Participants
Time Frame: Day 1 to Day 364
|
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).
|
Day 1 to Day 364
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2008
Primary Completion (Actual)
March 1, 2009
Study Completion (Actual)
September 1, 2012
Study Registration Dates
First Submitted
December 19, 2007
First Submitted That Met QC Criteria
December 19, 2007
First Posted (Estimate)
December 21, 2007
Study Record Updates
Last Update Posted (Estimate)
January 17, 2014
Last Update Submitted That Met QC Criteria
December 16, 2013
Last Verified
December 1, 2013
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IM103-047
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Renal Transplantation
-
Astellas Pharma IncAstellas Pharma Europe B.V.CompletedKidney Transplantation | Renal Transplantation | Transplantation, Kidney | Grafting, Kidney | Transplantation, RenalBelgium, Germany, Spain, Sweden, Italy, Switzerland, United Kingdom, Austria, France, Poland, Czech Republic, Netherlands
-
National Institute of Allergy and Infectious Diseases...PPD; Rho Federal Systems Division, Inc.; Immune Tolerance Network (ITN)Active, not recruitingKidney Transplantation | Renal Transplantation | Renal Transplant RecipientUnited States
-
Astellas Pharma Korea, Inc.CompletedKidney Transplantation | Renal Transplantation | Stable Renal RecipientsKorea, Republic of
-
University of Oslo School of PharmacyCompletedHeart Transplantation | Renal TransplantationNorway
-
NovartisCompletedOrgan Transplantation, Renal Transplantation
-
National Institute of Allergy and Infectious Diseases...Clinical Trials in Organ TransplantationTerminatedKidney Transplantation | Renal TransplantationUnited States
-
National Institute of Allergy and Infectious Diseases...Immune Tolerance Network (ITN)CompletedKidney Transplantation | Renal Transplant | Renal Transplantation | Transplant Rejection | Transplant ToleranceUnited States
-
University of North Carolina, Chapel HillMallinckrodtWithdrawnKidney Transplantation | Renal Transplantation | FSGSUnited States
-
Bristol-Myers SquibbCompletedKidney Transplantation | Graft Rejection | Renal TransplantationUnited States
-
Rabin Medical CenterRecruitingRenal TransplantationIsrael
Clinical Trials on Belatacept
-
Bristol-Myers SquibbCompletedRenal TransplantationUnited States
-
Guizhou Provincial People's HospitalActive, not recruiting
-
Bristol-Myers SquibbCompletedKidney Transplantation | Chronic Kidney FailureUnited States, Argentina, Australia, Germany, Italy, South Africa, Spain, Brazil, Mexico, Belgium, France, Hungary, Switzerland, India, Canada, Austria, Czech Republic, Poland, Israel, Sweden, Turkey
-
Methodist Health SystemActive, not recruitingUse of Belatacept in Kidney Transplant PatientsUnited States
-
Bristol-Myers SquibbCompletedRenal TransplantationUnited States, Argentina, Germany, Italy, Chile, Spain, Brazil, Sweden, Belgium, France, Hungary, Australia, South Africa, Austria, Canada, United Kingdom, Poland, Czechia, Norway
-
Bristol-Myers SquibbCompletedHealthy VolunteersUnited States
-
Bristol-Myers SquibbCompletedRheumatoid ArthritisUnited States, Netherlands, Belgium, Canada, Germany, France, Ireland, Switzerland, United Kingdom
-
Bristol-Myers SquibbTerminatedImmunosuppression in Solid Organ TransplantFrance, Germany, Italy, United States, Austria, Canada, Spain, Argentina, Brazil
-
University of MarylandBristol-Myers SquibbCompletedEnd-Stage Renal DiseaseUnited States
-
Ain Shams UniversityRecruiting