Renal Transplant RejectionPhase 4NCT01953120
Mechanisms of Belatacept Effect on Alloimmunity and Antiviral Response After Kidney Transplantation (BMS IM 103-309)
A Phase 4 study testing Belatacept in people with Renal Transplant Rejection, run by University of California, Los Angeles at 1 site in United States.
Trial summary
This research evaluates the effectiveness of a new drug called belatacept (Nulojix) for the prevention of acute rejection and preservation of kidney function in transplant patients. Belatacept was approved in 2011 by the United States Food and Drug Administration (FDA) and is being marketed as Nulojix. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Transplant Rejection
- 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
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to 21 Apr 2021
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The subject is willing to provide signed written informed consent Target Population
- The subject is a first-time recipient of a living or deceased donor kidney transplant
- Evidence of calcineurin inhibitor side effects during the first 3 months after transplant as defined as
- 1. Neurologic toxicity, defined as tremor, altered mental status, or seizure 2. Renal toxicity, defined as glomerular filtration rate (GFR) <60 3. Metabolic toxicity, defined as a new requirement for medication to control hyperglycemia 4. Hematologic toxicity, defined as development of thrombotic microangiopathy Age and Gender 4) Men and women, ages 18 and older, inclusive 5) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. Refer to the protocol for details regarding description and handling of WOCBP subjects.
- WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)) within 72 hours prior to the start of study medication then every 3 months during the period of study participation.
- 6) Men must use an adequate method of contraception throughout the study, and for up to 8 weeks after the last infusion, so that the risk of pregnancy to their partners is minimized.
- 7) Mycophenolate mofetil (MMF) must be dosed at 500 mg by mouth twice daily or greater at the time of study entry 8) Prednisone must be dosed at >=10 mg by mouth daily for patients less than 6 weeks post-transplantation, and at >=5mg by mouth daily for patients greater than 6 weeks post-transplantation at the time of study entry.
Who cannot join
- WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last infusion.
- Women who are pregnant or breastfeeding
- Women with a positive pregnancy test on enrollment or prior to study drug administration
- Males unwilling or unable to use an adequate method of contraception for the entire study period and for up to 8 weeks after the last infusion of study medication Immunologic status
- Subjects with panel reactive antibody (PRA) ≥ 30% at time of transplant
- Subjects with zero human leukocyte antigen (HLA) mismatched donors (either from related or unrelated donor)
Show all 18Show fewer
- Subjects with any prior solid organ transplant (including kidney)
- Subjects receiving a concurrent solid organ (heart, liver, pancreas) or cell (islet, bone marrow, stem cell) transplant
- Subjects with a history of biopsy-proven acute rejection post-transplant (humoral or cellular) in the first three months post transplantation Infection related risks
- Subjects who are hepatitis C antibody-positive or polymerase chain reaction (PCR)-positive for hepatitis C
- Subjects who are hepatitis B surface antigen-positive or PCR-positive for hepatitis B
- Subjects with known human immunodeficiency virus (HIV) infection
- Subjects with active tuberculosis (TB) requiring treatment within the previous 3 years or any subject who previously required triple (or more) combination therapy for TB.
- Subjects who are Epstein-Barr virus (EBV) antibody negative and have received grafts from EBV antibody positive donors.
- Prohibited Therapies and/or Medications
- Subjects who have used any investigational drug within 30 days prior to the Day 1 visit
- Subjects previously treated with belatacept
- Use of mammilian target of rapamycin (mTOR) inhibitors at any time after transplantation
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA Kidney Transplant Research
Los Angeles, California, 90024
About this study
Official title: Mechanisms of Belatacept (Nulojix) Effect on Alloimmunity and Antiviral Response After Kidney Transplantation - (BMS Study# IM 103-309)
This research evaluates the effectiveness of a new drug called belatacept (Nulojix) for the prevention of acute rejection and preservation of kidney function in transplant patients. Belatacept was approved in 2011 by the United States Food and Drug Administration (FDA) and is being marketed as Nulojix. The pharmaceutical company sponsoring this study is Bristol-Myers Squibb.
Belatacept is a prescription medicine used in adults to prevent transplant rejection in people who have received a kidney transplant. Transplant rejection happens when the body's immune system senses that the new transplanted kidney is different or foreign, and attacks it. Belatacept is used with corticosteroids and certain other medicines to help prevent rejection of your new kidney.
The purpose of the research is to understand whether the new drug, belatacept, is better than other anti-rejection drugs, such as cyclosporine and tacrolimus that are typically used in the treatment against kidney rejection in transplant patients.
Read the detailed description
Research Hypothesis: Switching to a belatacept-based immunosuppression regimen after kidney transplant will have a significant impact on antibody and T cell-mediated immune response as compared with control patients as measured in peripheral blood at 6 months after belatacept switch and comparable safety and efficacy as compared with calcineurin inhibitor (CNI) based regimens.
Primary Objective: To analyze the effect of switching from CNI to belatacept in patients with evidence of CNI toxicity on the development and maintenance of immune memory in response to both alloantigen and viral antigens commonly encountered after transplant, and to assess the safety and efficacy of conversion to belatacept as maintenance immunosuppression in combination with prednisone and mycophenolate mofetil.
Study Design: Open label, single center clinical trial. Patients with evidence of CNI toxicity will be eligible for switch to belatacept-based regimen within the first three months after transplant. All enrolled subjects will also receive concomitant maintenance immunosuppression with mycophenolate mofetil and corticosteroids.
Duration of Study: 6 months, with option to extend to 12 months of belatacept treatment Number of Subjects: 20 Study Population: Kidney transplant recipients within the first three months of their first transplant with evidence of CNI toxicity.
Test Product, Dose and Mode of Administration, Duration of Treatment: Study patients will receive intravenous belatacept at 5mg/kg every two weeks at day 1 and weeks 2, 4, 6, and 8, and then monthly at months 3, 4, and 5. At month 6 patients may elect to continue for an additional six month period of belatacept administration. Peripheral blood mononuclear cells (PBMCs) and sera for antibody testing will be collected at time of study entry and at 4, 8, 12, and 24 weeks after belatacept start, frozen and banked at our center, and analyzed in batch fashion for development of humoral and cell mediated immunity. Patients who elect to receive an additional 6 months of belatacept treatment will undergo additional immunologic analysis at 1 year after study entry.
- Conditions
- Renal Transplant Rejection
- 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 Nulojix
Subjects will receive intravenous belatacept at 5mg/kg every other week starting from day 1 and continuing with weeks 2, 4, 6, and 8, and then monthly at months 3, 4, 5, and 6. At month 6 patients may elect to continue for an additional six-month period of belatacept administration.
| Study group | Role | What they receive |
|---|---|---|
| Belatacept | Experimental | Survival and rejection in patients switched to belatacept. Receives: Drug: Belatacept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Antibody and T Cell-mediated Immune Response
To analyze the effect of switching from CNI to belatacept in patients with evidence of CNI toxicity on the development and maintenance of immune memory in response to both alloantigen and viral antigens commonly encountered after transplant, and to assess the safety and efficacy of conversion to belatacept as maintenance immunosuppression in combination with prednisone and mycophenolate mofetil.
Measured: Month 6
Secondary outcomes (1)
Post-transplant de Novo Donor Specific Antibody (DSA)
Incidence of de novo DSA detected at one or more time points during the period of study
Measured: Months 1, 3, and 12 if applicable as the secondary measures continue belatacept treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2013 (estimated)
- Study startOct 2013
- Primary completionApr 2021
- Study completion21 Apr 2021
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal Transplant RejectionStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, Suphamai Bunnapradist, University of California, Los Angeles
- Investigators
- Suphamai Bunnapradist, M.D., Principal investigator, UCLA Kidney Transplant Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01953120
- Sponsor's protocol ID
- 13-000270
- Status last verified
- Nov 2022
- First submitted
- 25 Sep 2013
- Last updated
- 13 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Schaenman J, Rossetti M, Pickering H, Sunga G, Wilhalme H, Elashoff D, Zhang Q, Hickey M, Reddy U, Danovitch G, Reed EF, Bunnapradist S. Preservation of Antiviral Immunologic Efficacy Without Alloimmunity After Switch to Belatacept in Calcineurin Inhibitor-Intolerant Patients. Kidney Int Rep. 2022 Oct 20;8(1):126-140. doi: 10.1016/j.ekir.2022.10.015. eCollection 2023 Jan.
PubMed 36644348
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Belatacept (Nulojix) Effect on Alloimmunity and Antiviral Response After Kidney Transplantation - (BMS Study# IM 103-309)
- ClinicalTrials.gov ID
- NCT01953120
- Acronym / sponsor ID
- 13-000270
- Conditions
- Renal Transplant Rejection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Oct 2013
- Primary completion
- Apr 2021 (actual)
- Study completion
- 21 Apr 2021 (actual)
- First posted
- 30 Sep 2013 (estimated)
- Results
- Posted 13 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research evaluates the effectiveness of a new drug called belatacept (Nulojix) for the prevention of acute rejection and preservation of kidney function in transplant patients. Belatacept was approved in 2011 by the United States Food and Drug Administration (FDA) and is being marketed as Nulojix. The pharmaceutical company sponsoring this study is Bristol-Myers Squibb.
Belatacept is a prescription medicine used in adults to prevent transplant rejection in people who have received a kidney transplant. Transplant rejection happens when the body's immune system senses that the new transplanted kidney is different or foreign, and attacks it. Belatacept is used with corticosteroids and certain other medicines to help prevent rejection of your new kidney.
The purpose of the research is to understand whether the new drug, belatacept, is better than other anti-rejection drugs, such as cyclosporine and tacrolimus that are typically used in the treatment against kidney rejection in transplant patients.
Detailed description
Research Hypothesis: Switching to a belatacept-based immunosuppression regimen after kidney transplant will have a significant impact on antibody and T cell-mediated immune response as compared with control patients as measured in peripheral blood at 6 months after belatacept switch and comparable safety and efficacy as compared with calcineurin inhibitor (CNI) based regimens.
Primary Objective: To analyze the effect of switching from CNI to belatacept in patients with evidence of CNI toxicity on the development and maintenance of immune memory in response to both alloantigen and viral antigens commonly encountered after transplant, and to assess the safety and efficacy of conversion to belatacept as maintenance immunosuppression in combination with prednisone and mycophenolate mofetil.
Study Design: Open label, single center clinical trial. Patients with evidence of CNI toxicity will be eligible for switch to belatacept-based regimen within the first three months after transplant. All enrolled subjects will also receive concomitant maintenance immunosuppression with mycophenolate mofetil and corticosteroids.
Duration of Study: 6 months, with option to extend to 12 months of belatacept treatment Number of Subjects: 20 Study Population: Kidney transplant recipients within the first three months of their first transplant with evidence of CNI toxicity.
Test Product, Dose and Mode of Administration, Duration of Treatment: Study patients will receive intravenous belatacept at 5mg/kg every two weeks at day 1 and weeks 2, 4, 6, and 8, and then monthly at months 3, 4, and 5. At month 6 patients may elect to continue for an additional six month period of belatacept administration. Peripheral blood mononuclear cells (PBMCs) and sera for antibody testing will be collected at time of study entry and at 4, 8, 12, and 24 weeks after belatacept start, frozen and banked at our center, and analyzed in batch fashion for development of humoral and cell mediated immunity. Patients who elect to receive an additional 6 months of belatacept treatment will undergo additional immunologic analysis at 1 year after study entry.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Belatacept | Experimental | Drug: BelataceptSurvival and rejection in patients switched to belatacept. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- The subject is willing to provide signed written informed consent Target Population
- The subject is a first-time recipient of a living or deceased donor kidney transplant
- Evidence of calcineurin inhibitor side effects during the first 3 months after transplant as defined as
- 1. Neurologic toxicity, defined as tremor, altered mental status, or seizure 2. Renal toxicity, defined as glomerular filtration rate (GFR) <60 3. Metabolic toxicity, defined as a new requirement for medication to control hyperglycemia 4. Hematologic toxicity, defined as development of thrombotic microangiopathy Age and Gender 4) Men and women, ages 18 and older, inclusive 5) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. Refer to the protocol for details regarding description and handling of WOCBP subjects.
- WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)) within 72 hours prior to the start of study medication then every 3 months during the period of study participation.
Key exclusion criteria (18 listed)
- WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last infusion.
- Women who are pregnant or breastfeeding
- Women with a positive pregnancy test on enrollment or prior to study drug administration
- Males unwilling or unable to use an adequate method of contraception for the entire study period and for up to 8 weeks after the last infusion of study medication Immunologic status
- Subjects with panel reactive antibody (PRA) ≥ 30% at time of transplant
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: NulojixSubjects will receive intravenous belatacept at 5mg/kg every other week starting from day 1 and continuing with weeks 2, 4, 6, and 8, and then monthly at months 3, 4, 5, and 6. At month 6 patients may elect to continue for an additional six-month period of belatacept administration. | Drug | Belatacept |
Primary outcome
Antibody and T Cell-mediated Immune Response
Time frame: Month 6
To analyze the effect of switching from CNI to belatacept in patients with evidence of CNI toxicity on the development and maintenance of immune memory in response to both alloantigen and viral antigens commonly encountered after transplant, and to assess the safety and efficacy of conversion to belatacept as maintenance immunosuppression in combination with prednisone and mycophenolate mofetil.
1 secondary outcome
Post-transplant de Novo Donor Specific Antibody (DSA)
Time frame: Months 1, 3, and 12 if applicable as the secondary measures continue belatacept treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36644348Schaenman J, Rossetti M, Pickering H, Sunga G, Wilhalme H, Elashoff D, Zhang Q, Hickey M, Reddy U, Danovitch G, Reed EF, Bunnapradist S. Preservation of Antiviral Immunologic Efficacy Without Alloimmunity After Switch to Belatacept in Calcineurin Inhibitor-Intolerant Patients. Kidney Int Rep. 2022 Oct 20;8(1):126-140. doi: 10.1016/j.ekir.2022.10.015. eCollection 2023 Jan.
- Individual participant dataSharing planned: No
Related trials for Renal Transplant Rejection
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney
Not yet recruitingPhase 2
(TNX-1500) in Kidney Transplant Recipients
Kidney Transplant, Kidney Transplant Failure and Rejection
RecruitingPhase 2
A Study to Learn About the Effects of Felzartamab Infusions in Adults With Kidney Transplants Who Have Late Isolated Microvascular Inflammation
Microvascular Inflammation
Not yet recruitingObservational study
Assessment of Perceived Stress in an Observational Study Evaluating a Biopsy-sparing Surveillance Strategy in Kidney Transplant Recipients With Blood and Urinary Biomarkers Predictive of the Absence of Rejection
Renal Transplantation; Complication, Renal Transplant
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.
Suphamai Bunnapradist, M.D. principal investigator
UCLA Kidney Transplant Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Belatacept in people with Renal Transplant Rejection, run by University of California, Los Angeles at 1 site 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 7 inclusion and 18 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 13 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 13 Dec 2022). 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?
Antibody and T Cell-mediated Immune Response (time frame: Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01953120, which also lists 1 linked publication.
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 13 Dec 2022.