Kidney TransplantPhase 2NCT01791491
Pharmacokinetics, Safety and Tolerability of Single-dose Belatacept in Adolescent Kidney Transplant Recipients
A Phase 2 study testing Belatacept in people with Kidney Transplant, run by Bristol-Myers Squibb at 8 sites in United States.
Trial summary
The purpose of this study is to evaluate how well adolescent kidney transplant patients tolerate a single dose of belatacept they receive at least 6 months after transplant surgery, and how their body handles the drug. Read more about this study
- Who is it for?
- Ages 12 to 17 years
- Conditions the study is for
- Kidney Transplant
- What is being tested?
- Belatacept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 8 sitesUnited States
- Study dates
- 9 May 2013to 6 Dec 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male and Female subjects,12-17 years old
- Receiving CNI-based maintenance immunosuppression since the time of renal transplantation in accordance with local standard of care
- Stable renal function, in the opinion of the investigator, with a cGFR>45 mL/min/1.73m2 at the time of enrollment (per updated Schwartz Formula)
- Adolescent Recipients of a renal allograft from a living donor or a deceased donor at least 6 months prior to enrollment
- Subject must be receiving a calcineurin inhibitor (CNI)-based [cyclosporine (CsA) [any formulation] or Tacrolimus (TAC)] immunosuppressive regimen
- Subject must be receiving adjunctive background maintenance immunosuppression with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS)/mycophenolic acid (MPA)
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- Subjects may be receiving maintenance corticosteroids in accordance with the local standard of care
- Negative Interferon Gamma Release Assay (IGRA) such as QuantiFERON-TB Gold test or T-Spot-TB
- FOCBP must have negative serum or urine pregnancy test within 24 hrs prior to start of study medication
- Subject must have stable estimated glomerular filtration rate (GFR) ≥45 mL/min/1.73m2 (updated Schwartz formula)
Who cannot join
- Epstein-Barr virus (EBV) serostatus negative or unknown at time of transplant and screening
- History of any treated or biopsy proven acute rejection (BPAR) within 3 months prior to enrollment
- Subjects who have experienced more than 1 episode of acute rejection (AR) of the current allograft or any antibody-mediated AR
- Subjects with any active infection [including, but not limited to, positive cytomegalovirus (CMV) or BK viral (BKV) loads, BKV associated nephropathy (BKVAN), CMV retinitis, CMV colitis, etc.]
- Urine albumin:creatinine ratio > 56.5 mg/mmol (> 0.5 mg albumin / mg creatinine) on a random voided urine specimen
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Emory University
Atlanta, Georgia, 30322
University Of Alabama At Birmingham
Birmingham, Alabama, 35233
Boston Childrens Hospital
Boston, Massachusetts, 02115
Childrens Hospital Of La
Los Angeles, California, 90027
University Of California Los Angeles
Los Angeles, California, 90095
Washington University
St Louis, Missouri, 63110
Stanford University Medical Center
Stanford, California, 94305
Childrens National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase 2 Multi-Center, Randomized Conversion Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Belatacept Administered to Pediatric Subjects With a Stable Renal Transplant
The purpose of this study is to evaluate how well adolescent kidney transplant patients tolerate a single dose of belatacept they receive at least 6 months after transplant surgery, and how their body handles the drug.
- Conditions
- Kidney Transplant
- Being tested
- Belatacept
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelataceptDrug
Also called BMS-224818
Single intravenous infusion of belatacept, 7.5 mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Belatacept | Experimental | Not described Receives: Drug: Belatacept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Serum Concentration (Cmax) of Belatacept
Cmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Cmax was measured in micrograms per milliliter.
Measured: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Time of Maximum Observed Plasma Concentration (Tmax) of Belatacept
Tmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Tmax was measured in hours (h).
Measured: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Half-Life of Elimination (T-Half) of Belatacept
T-HALF was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). T-HALF was measured in hours (h).
Measured: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC (0-T)) and Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Belatacept
AUC (0 - T) and AUC (0 - INF) were derived from serum concentration versus time data and measured in microgram hours per milliliter (µg*h/mL). Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL).
Measured: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Total Body Clearance (CLT) of Belatacept
CLT was the volume of abatacept cleared by the system, normalized by baseline body weight. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). CLT was measured in milliliters per hours per kilogram of body weight (mL/h/kg).
Measured: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Volume of Distribution at Steady-state (Vss) of Belatacept
Vss was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Vss was measured in liters per kg body weight (L/kg).
Measured: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Secondary outcomes (3)
Number of Participants With Death, Serious Adverse Events (SAEs), and Treatment-related Adverse Event (AE)
Death was a fatal event leading to permanent cessations of all vital functions of the body. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Treatment related=having certain, probable, possible, or missing relationship to study drug.
Measured: Date of First Dose to 24 weeks post the last dose; approximately 26 weeks
Number of Participants With Positive Belatacept-induced Immunogenicity Response
Serum samples were analyzed for anti-belatacept antibodies using a validated homogenous bridging assay. The assay followed a tiered approach consistent with health authority guidance: tier 1 for screening ADA responses, tier 2 for confirming drug specificity of the ADA-positive responses, and tier 3 for titer. A neutralizing antibody assay was used to test those samples positive to the LEA29Y portion of the molecule in tier 2 and for which drug concentrations are =>1 μg/mL. Lack of immunogenicity was defined as the absence of a positive response.
Measured: Baseline/Day 1, Days 15, 29, and 57
Percentage of CD86 Receptor Occupancy
Blood samples collected following the single dose belatacept infusion were assessed for CD86 receptor occupancy (CD86 RO).
Measured: 0.5 hours post dose on Day 1, Day 29 and Day 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2013 (estimated)
- Study start9 May 2013
- Primary completion6 Dec 2016
- Study completion6 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Kidney TransplantStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01791491
- Sponsor's protocol ID
- IM103-144
- Other IDs
- 2011-005257-31
- Status last verified
- Jun 2017
- First submitted
- 31 Jan 2013
- Last updated
- 24 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Multi-Center, Randomized Conversion Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Belatacept Administered to Pediatric Subjects With a Stable Renal Transplant
- ClinicalTrials.gov ID
- NCT01791491
- Acronym / sponsor ID
- IM103-144
- Conditions
- Kidney Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 9 May 2013 (actual)
- Primary completion
- 6 Dec 2016 (actual)
- Study completion
- 6 Dec 2016 (actual)
- First posted
- 15 Feb 2013 (estimated)
- Results
- Posted 26 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate how well adolescent kidney transplant patients tolerate a single dose of belatacept they receive at least 6 months after transplant surgery, and how their body handles the drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Belatacept | Experimental | Drug: Belatacept |
Who may qualify
- Ages
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- Male and Female subjects,12-17 years old
- Receiving CNI-based maintenance immunosuppression since the time of renal transplantation in accordance with local standard of care
- Stable renal function, in the opinion of the investigator, with a cGFR>45 mL/min/1.73m2 at the time of enrollment (per updated Schwartz Formula)
- Adolescent Recipients of a renal allograft from a living donor or a deceased donor at least 6 months prior to enrollment
- Subject must be receiving a calcineurin inhibitor (CNI)-based [cyclosporine (CsA) [any formulation] or Tacrolimus (TAC)] immunosuppressive regimen
Key exclusion criteria (5 listed)
- Epstein-Barr virus (EBV) serostatus negative or unknown at time of transplant and screening
- History of any treated or biopsy proven acute rejection (BPAR) within 3 months prior to enrollment
- Subjects who have experienced more than 1 episode of acute rejection (AR) of the current allograft or any antibody-mediated AR
- Subjects with any active infection [including, but not limited to, positive cytomegalovirus (CMV) or BK viral (BKV) loads, BKV associated nephropathy (BKVAN), CMV retinitis, CMV colitis, etc.]
- Urine albumin:creatinine ratio > 56.5 mg/mmol (> 0.5 mg albumin / mg creatinine) on a random voided urine specimen
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BelataceptAlso: BMS-224818Single intravenous infusion of belatacept, 7.5 mg/kg | Drug | Belatacept |
Primary outcome
Maximum Observed Serum Concentration (Cmax) of Belatacept
Time frame: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Cmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Cmax was measured in micrograms per milliliter.
Time of Maximum Observed Plasma Concentration (Tmax) of Belatacept
Time frame: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Tmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Tmax was measured in hours (h).
Half-Life of Elimination (T-Half) of Belatacept
Time frame: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
T-HALF was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). T-HALF was measured in hours (h).
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC (0-T)) and Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Belatacept
Time frame: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
AUC (0 - T) and AUC (0 - INF) were derived from serum concentration versus time data and measured in microgram hours per milliliter (µg*h/mL). Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL).
Total Body Clearance (CLT) of Belatacept
Time frame: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
CLT was the volume of abatacept cleared by the system, normalized by baseline body weight. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). CLT was measured in milliliters per hours per kilogram of body weight (mL/h/kg).
Volume of Distribution at Steady-state (Vss) of Belatacept
Time frame: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Vss was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Vss was measured in liters per kg body weight (L/kg).
3 secondary outcomes
Number of Participants With Death, Serious Adverse Events (SAEs), and Treatment-related Adverse Event (AE)
Time frame: Date of First Dose to 24 weeks post the last dose; approximately 26 weeks
Number of Participants With Positive Belatacept-induced Immunogenicity Response
Time frame: Baseline/Day 1, Days 15, 29, and 57
Percentage of CD86 Receptor Occupancy
Time frame: 0.5 hours post dose on Day 1, Day 29 and Day 57
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belatacept in people with Kidney Transplant, run by Bristol-Myers Squibb at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Observed Serum Concentration (Cmax) of Belatacept (time frame: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2017.