ProteinuriaPhase 2NCT02327403
Belatacept Conversion in Proteinuric Kidney Transplant Recipients
A Phase 2 study testing Belatacept in people with Proteinuria, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Background: Proteinuria develops in about 30% of kidney transplant recipients and is a strong predictor of graft loss. The amount of proteinuria has a direct correlation with the risk of graft failure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Proteinuria
- What is being tested?
- Belatacept
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to 1 Oct 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female adult kidney transplant recipients older than 18 years old
- eGFR ≥30 ml/min
- ≥6 months after transplantation
- Proteinuria ≥1 gram/day in spot urine protein/creatinine ratio
- Ability to provide written informed consent for the study.
- Maintenance immunosuppression of CNI (cyclosporine or tacrolimus), antiproliferative agent (azathioprine, MMF or MPA) with either steroids or not.
Who cannot join
- Age <18 years
- eGFR<30 ml/min
- active acute cellular rejection (ACR; higher than borderline) or ACR in the previous 6 months; active acute antibody-mediated rejection
- recurrent FSGS
- EBV IgG negative
- patient on mTOR inhibitor (e.g. Everolimus, Sirolimus)
- patient only on CNI (cyclosporine or tacrolimus) and steroids
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: The B7-1 Study": Belatacept Conversion in Proteinuric Renal Transplant Recipients: an Interventional Multi-Center Trial
Background: Proteinuria develops in about 30% of kidney transplant recipients and is a strong predictor of graft loss. The amount of proteinuria has a direct correlation with the risk of graft failure. Novel therapies are urgently needed to reduce proteinuria and prevent graft loss in transplant recipients, since ACE inhibitors carry a number of limitations in the transplant setting, including significant reduction in renal function, anemia and hyperkalemia.
Preliminary data: B7-1 is expressed at significant levels in about 10% of kidney allograft biopsies with predominance in patients with proteinuria.
Read more
Hypothesis: We hypothesize that B7-1 targeting therapy may reduce proteinuria and improve graft survival in proteinuric transplant recipients that have B7-1 staining on allografts. In addition, the absence of CNI nephrotoxicity and the potential protective effect of Belatacept on DSA production may be of benefit in this subset of transplant patients.
Objectives:
Primary: Determine the effect of Belatacept conversion in reducing proteinuria by 25% at 12 months in renal transplant recipients (≥1gram/d) that are either B7-1-positive or negative on kidney biopsy.
Secondary: Assess the effect of Belatacept conversion in the percent change of renal function from baseline to 12 months; donor-specific anti-HLA antibodies presence and intensity (MFI); correlation of B7-1 positivity on immunofluorescence on biopsy with B7-1-expression in urine extracellular vesicles; adverse events; acute rejection episodes; blood pressure control; new onset diabetes; hyperlipidemia; graft survival; and patient survival.
Read the detailed description
A total of 36 patients will be recruited.
- Conditions
- Proteinuria
- Being tested
- Belatacept
- Keywords
- Proteinuria, Kidney transplantation, Allograft dysfunction, B7-1, Belatacept
- Medical subject headings
- Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelataceptDrug
Conversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression.
| Study group | Role | What they receive |
|---|---|---|
| Proteinuric Kidney Transplant Recipients | Experimental | Belatacept conversion Receives: Drug: Belatacept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Proteinuria by 25%
Change in proteinuria by 25%: daily proteinuria is estimated by spot urine protein (mg/dL) to creatinine (mg/dL) ratio at baseline (before the belatacept conversion) and post-conversion 12 months; and interval % change was calculated by getting the ratio of difference between the two time points to the baseline value.
Measured: 12 months
Secondary outcomes (7)
Change in Renal Function (eGFR in mL/Min/1.73 m^2)
Measured: from baseline to 12 months
Acute Rejection Episodes
Acute rejection episodes [Time Frame: 12 months]: Number of biopsy-proven rejection episodes from belatacept conversion to post-conversion 12 months.
Measured: 12 months
Change in Blood Pressure Measurement (mm Hg)
Change in Blood pressure measurement (mm Hg) [Time Frame: 12 months]: The mmHg difference in systolic and diastolic blood pressures between the baseline (pre-belatacept conversion) and post-conversion 12 months is assessed. Blood pressure measurement done at the office visits at baseline and 12 months after at least 5 minutes of resting.
Measured: 12 months
Change in Fasting Glucose
New onset diabetes [Time Frame: 12 months]: Number of new onset diabetes per American Diabetes Association 2015 Criteria from belatacept conversion to post-conversion 12 months
Measured: 12 months
Hyperlipidemia
Hyperlipidemia [ Time Frame: 12 months]: Changes (mg/dL) in serum total cholesterol, LDL, HDL, and triglyceride levels from pre-belatacept conversion to post-conversion 12 months.
Measured: 12 months
Graft Survival
Graft survival [Time Frame: 12 months]: Number of patients who developed end stage kidney disease and required kidney replacement therapy within 12 months post-belatacept conversion.
Measured: 12 months
Patient Survival
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2014 (estimated)
- Study startOct 2015
- Primary completionSep 2020
- Study completion1 Oct 2020
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 ProteinuriaStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, Leonardo V. Riella, MD PhD, Brigham and Women's Hospital
- Investigators
- Leonardo V Riella, MD, PhD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02327403
- Sponsor's protocol ID
- 2015P000154
- Status last verified
- Oct 2022
- First submitted
- 22 Dec 2014
- Last updated
- 9 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The B7-1 Study": Belatacept Conversion in Proteinuric Renal Transplant Recipients: an Interventional Multi-Center Trial
- ClinicalTrials.gov ID
- NCT02327403
- Acronym / sponsor ID
- 2015P000154
- Conditions
- Proteinuria
- Keywords
- Proteinuria, Kidney transplantation, Allograft dysfunction, B7-1, Belatacept
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Oct 2015 (actual)
- Primary completion
- Sep 2020 (actual)
- Study completion
- 1 Oct 2020 (actual)
- First posted
- 30 Dec 2014 (estimated)
- Results
- Posted 9 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: Proteinuria develops in about 30% of kidney transplant recipients and is a strong predictor of graft loss. The amount of proteinuria has a direct correlation with the risk of graft failure. Novel therapies are urgently needed to reduce proteinuria and prevent graft loss in transplant recipients, since ACE inhibitors carry a number of limitations in the transplant setting, including significant reduction in renal function, anemia and hyperkalemia.
Preliminary data: B7-1 is expressed at significant levels in about 10% of kidney allograft biopsies with predominance in patients with proteinuria.
Hypothesis: We hypothesize that B7-1 targeting therapy may reduce proteinuria and improve graft survival in proteinuric transplant recipients that have B7-1 staining on allografts. In addition, the absence of CNI nephrotoxicity and the potential protective effect of Belatacept on DSA production may be of benefit in this subset of transplant patients.
Objectives:
Primary: Determine the effect of Belatacept conversion in reducing proteinuria by 25% at 12 months in renal transplant recipients (≥1gram/d) that are either B7-1-positive or negative on kidney biopsy.
Secondary: Assess the effect of Belatacept conversion in the percent change of renal function from baseline to 12 months; donor-specific anti-HLA antibodies presence and intensity (MFI); correlation of B7-1 positivity on immunofluorescence on biopsy with B7-1-expression in urine extracellular vesicles; adverse events; acute rejection episodes; blood pressure control; new onset diabetes; hyperlipidemia; graft survival; and patient survival.
Detailed description
A total of 36 patients will be recruited.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Proteinuric Kidney Transplant Recipients | Experimental | Drug: BelataceptBelatacept conversion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female adult kidney transplant recipients older than 18 years old
- eGFR ≥30 ml/min
- ≥6 months after transplantation
- Proteinuria ≥1 gram/day in spot urine protein/creatinine ratio
- Ability to provide written informed consent for the study.
Key exclusion criteria (7 listed)
- Age <18 years
- eGFR<30 ml/min
- active acute cellular rejection (ACR; higher than borderline) or ACR in the previous 6 months; active acute antibody-mediated rejection
- recurrent FSGS
- EBV IgG negative
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 |
|---|---|---|
| BelataceptConversion from calcineurin-inhibitor to Belatacept maintenance immunosuppression. | Drug | Proteinuric Kidney Transplant Recipients |
Primary outcome
Change in Proteinuria by 25%
Time frame: 12 months
Change in proteinuria by 25%: daily proteinuria is estimated by spot urine protein (mg/dL) to creatinine (mg/dL) ratio at baseline (before the belatacept conversion) and post-conversion 12 months; and interval % change was calculated by getting the ratio of difference between the two time points to the baseline value.
7 secondary outcomes
Change in Renal Function (eGFR in mL/Min/1.73 m^2)
Time frame: from baseline to 12 months
Acute Rejection Episodes
Time frame: 12 months
Change in Blood Pressure Measurement (mm Hg)
Time frame: 12 months
Change in Fasting Glucose
Time frame: 12 months
Hyperlipidemia
Time frame: 12 months
Graft Survival
Time frame: 12 months
Patient Survival
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Proteinuria
Enrolling by invitationObservational study
An Observational Post-Authorization Safety and Effectiveness Study of Ravulizumab in Adult Patients Aged 18 and Older Diagnosed With Paroxysmal Nocturnal Hemoglobinuria Using Multicenter Electronic Medical Records in South Korea
Hemoglobinuria, Paroxysmal
Not yet recruitingObservational study
Obesity-Related Indices and Albuminuria in Type 2 Diabetes
Obesity and Diabetes Mellitus, Type 2, Albuminuria
Active, not recruitingObservational study
Family Investigation of Nephropathy and Diabetes (F.I.N.D.)
Diabetic Nephropathy, Diabetes Mellitus
RecruitingPhase 3
Study of Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy.
C3G
RecruitingObservational study
Hypertension in Children and Young People at Risk of Autosomal Dominant Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease (ADPKD
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.
Leonardo V Riella, MD, PhD principal investigator
Brigham and Women's Hospital
1 site 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 Proteinuria, run by Brigham and Women's Hospital 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 6 inclusion and 7 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 9 Nov 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 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 9 Nov 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?
Change in Proteinuria by 25% (time frame: 12 months). 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 9 Nov 2022.