belatacept for Highly Sensitized Prospective Kidney Transplant Recipients

Phase-Based Progress Estimates
1
Effectiveness
1
Safety
Duke Transplant Center, Duke University Medical Center, Durham, NC
Highly Sensitized Prospective Kidney Transplant Recipients
belatacept - Biological
Eligibility
18+
All Sexes
Eligible conditions
Select

Study Summary

This study is evaluating whether two drugs can make kidney transplant candidates less sensitized.

See full description

Treatment Effectiveness

Effectiveness Progress

1 of 3

Other trials for Highly Sensitized Prospective Kidney Transplant Recipients

Study Objectives

This trial is evaluating whether belatacept will improve 2 primary outcomes and 14 secondary outcomes in patients with Highly Sensitized Prospective Kidney Transplant Recipients. Measurement will happen over the course of Baseline (Visit 0) to Week 20 post treatment initiation.

Week 20
Proportion of subjects who meet any one of the pre-specified events detailed in the outcome description: from Baseline to Week 20 post treatment initiation
Week 16
Mean number of Human Leukocyte Antigen (HLA) antibodies eliminated, compared to Baseline
Mean percent reduction from Baseline in mean fluorescence intensity (MFI) of Human Leukocyte Antigen (HLA) antibodies classified by an MFI >10,000 at treatment initiation
Mean percent reduction from Baseline in mean fluorescence intensity (MFI) of the immunodominant Human Leukocyte Antigen (HLA) antibody, Class I and Class II
Mean proportion of Human Leukocyte Antigen (HLA) antibodies eliminated, compared to Baseline
Week 20
Proportion of subjects who do not meet a stopping rule for safety and remain free of all of the safety events listed in the outcome description, through Week 20 post treatment initiation or until receiving a transplant, whichever occurs earlier
Week 20
Incidence of cytomegalovirus (CMV) disease within 20 weeks after starting treatment
Incidence of cytomegalovirus (CMV) infection within 20 weeks after starting treatment
Incidence of invasive fungal infections, mycobacterial infections or Pneumocystis jirovecii infection within 20 weeks after starting treatment
Week 52
Incidence of cytomegalovirus (CMV) disease within 52 weeks after starting treatment
Incidence of cytomegalovirus (CMV) infection within 52 weeks after starting treatment
Incidence of invasive fungal infections, mycobacterial infections or Pneumocystis jirovecii infection within 52 weeks after starting treatment
Proportion of subjects transplanted with a previously incompatible donor within 52 weeks after starting treatment
Within 52 weeks post-transplant
Incidence of post-transplant lymphoproliferative disorder (PTLD)
Number of biopsy-proven acute or chronic AMR events within 52 weeks post-transplant in subjects who undergo a kidney transplant
Proportion of subjects with biopsy-proven acute or chronic antibody mediated rejection (AMR) within 52 weeks post-transplant in subjects who undergo a kidney transplant

Trial Safety

Safety Progress

1 of 3

Other trials for Highly Sensitized Prospective Kidney Transplant Recipients

Trial Design

2 Treatment Groups

Cohort 1 (N=5 Subjects)
1 of 2
Cohort 2 (N=10 Subjects)
1 of 2
Experimental Treatment

This trial requires 15 total participants across 2 different treatment groups

This trial involves 2 different treatments. Belatacept is the primary treatment being studied. Participants will be divided into 2 treatment groups. There is no placebo group. The treatments being tested are in Phase 1 & 2 and have already been tested with other people.

Cohort 1 (N=5 Subjects)The two investigational agents used in this study are carfilzomib and belatacept. Per protocol, Carfilzomib administered intravenously: Cycle 1 will consist of 2 doses in week 4 (Day 28 and 29). If tolerated, the dose will be increased and administered twice a week in weeks 5 (Day 35 and 36) and 6 (Day 42 and 43). Cycle 2 will consist of a total of 6 doses, administered twice weekly in weeks 12 (Day 84 and 85), 13 (Day 91 and 92) and 14 (Day 98 and 99). Per protocol, Belatacept: -Belatacept will be administered intravenously on days 29 (week 4), 33 (week 5), and weeks 6, 8, 12, 16, then at a lower dose at week 20, 24, 28, 32, 36, 40, 44, 48, 52, and 56. Dosing is based on the recommended dose in the package insert.
Cohort 2 (N=10 Subjects)The enrollment of ten additional subjects and dosing regimen is dependent on the results in Cohort 1.° Per protocol, Carfilzomib administered intravenously: Cycle 1 will consist of 2 doses in week 4 (Day 28 and 29). If tolerated, the dose will be increased and administered twice a week in weeks 5 (Day 35 and 36) and 6 (Day 42 and 43). Cycle 2 will consist of a total of 6 doses, administered twice weekly in weeks 12 (Day 84 and 85), 13 (Day 91 and 92) and 14 (Day 98 and 99). Per protocol, Belatacept: -Belatacept will be administered intravenously on days 29 (week 4), 33 (week 5), and weeks 6, 8, 12, 16, then at a lower dose at week 20, 24, 28, 32, 36, 40, 44, 48, 52, and 56. Dosing is based on the recommended dose in the package insert. ° May be modified based on the safety and efficacy analysis of Cohort 1.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Carfilzomib
FDA approved
Bone marrow aspiration
2000
Completed Phase 2
~260
Belatacept
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: baseline (visit 0), weeks 16, 20, and 52 post treatment initiation
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly baseline (visit 0), weeks 16, 20, and 52 post treatment initiation for reporting.

Closest Location

Duke Transplant Center, Duke University Medical Center - Durham, NC

Eligibility Criteria

This trial is for patients born any sex aged 18 and older. There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
is costly and severe People with ESRD on dialysis experience a high cost of care and a severe decline in health. show original
ation Most people who need a kidney transplant will have to wait for a deceased donor show original
97 percent of people currently waiting for a deceased donor transplant will have to wait more than five years. show original
98 percent of people who are currently in a kidney paired exchange program and have a human leukocyte antigen (HLA)-incompatible approved living donor have not received a transplant after 1 year. show original
Testing should be conducted using a purified protein derivative (PPD) or an interferon-gamma release assay (i.e show original
If someone has not been exposed to tuberculosis in the last year, any negative tests results from the past 12 months are acceptable. show original
-Male or female -Age 18 years or older -Good health People who are male or female and who are 18 years or older and who are in good health can be enrolled as study subjects. show original
The patient must be able to understand what is happening and provide consent that is knowledgeable and informed. show original
or by detection of EBV DNA in clinical specimens is not a contraindication to receipt of the zoster vaccine show original
The patient has either tested positive for tuberculosis in the most recent test or has not appropriately completed therapy for latent tuberculosis infection. show original

Patient Q&A Section

What are the signs of highly sensitized prospective kidney transplant recipients?

"The presence of class IV anti-class I antibodies is an independent predictor of immediate graft loss and increased incidence of acute rejection in highly sensitized recipients." - Anonymous Online Contributor

Unverified Answer

What is highly sensitized prospective kidney transplant recipients?

"We identified a significant risk of delayed graft function in highly sensitized recipients with ESRD. The main risk factors were pretransplant DSA and HLA class I positivity. Further study with a prospective design is needed to define the optimum HLA class II matching for these patients to reduce the incidence of DGF." - Anonymous Online Contributor

Unverified Answer

What causes highly sensitized prospective kidney transplant recipients?

"Highly sensitized recipients had a higher risk of having a history of exposure to the medications in question but this was not seen for highly sensitized recipients who were not exposed to this drug class. The role of the other drugs and their interactions cannot be excluded." - Anonymous Online Contributor

Unverified Answer

How many people get highly sensitized prospective kidney transplant recipients a year in the United States?

"The number of patients with HSP is growing and may be expected to grow. The high numbers of HSP, especially in men, could have adverse clinical consequences. HSP could represent a potential risk for patients who have recently participated in a kidney transplant." - Anonymous Online Contributor

Unverified Answer

What are common treatments for highly sensitized prospective kidney transplant recipients?

"Patients with highly sensitized (i.e. with a donor serum-level >3.0 units/L or >20 mm (mg/ml)) are at elevated risk of acute rejection and development of chronic antibody-mediated rejection which is difficult to treat. Early ciclosporin A-based immunosuppression combined with the use of HLA-mismatched living donor-human-lethals may be effective (i.e. reduction of the need for steroid bolus) but this regimen remains relatively uncommon and, where available, not always tolerated. Findings from a recent study should inform the medical management program of any renal transplantation in highly sensitized patients." - Anonymous Online Contributor

Unverified Answer

Can highly sensitized prospective kidney transplant recipients be cured?

"This prospective study demonstrates that high HSA levels, although associated with a higher incidence of rejection, do not confer additional risk to the long-term survival of highly sensitized patients, when managed by the standard steroid-based immunosuppressive regimen." - Anonymous Online Contributor

Unverified Answer

Is belatacept safe for people?

"Belatacept is generally well tolerated, with low discontinuation rates in a high risk patient population. Belatacept should be considered for treatment of end stage kidney disease in adults with high risk HLA seropositive patients. Given its efficacy and safety profile it warrants further investigation in a larger patient population. Clinicaltrials.gov NCT02806048." - Anonymous Online Contributor

Unverified Answer

How serious can highly sensitized prospective kidney transplant recipients be?

"Patients with sHCA have a considerable risk of posttransplant complications. A history of HCA, in conjunction with the panel assay, is a highly prognostically significant variable. In highly sensitized patients with two HCA, graft survival after living donor/living-related-donor kidney transplantation is comparable with that in patients without HCA on their recipients' systems." - Anonymous Online Contributor

Unverified Answer

Does belatacept improve quality of life for those with highly sensitized prospective kidney transplant recipients?

"Belatacept was associated with improvements in QoL and clinical response rates of HS patients in the first 6 months of treatment. These improvements are most likely attributed to belatacept exposure and early patient monitoring rather than belatacept treatment itself." - Anonymous Online Contributor

Unverified Answer

What is the primary cause of highly sensitized prospective kidney transplant recipients?

"Because HT was common, especially in patients who presented with HLA class I (HLA-01) mismatching, HLA-class I mismatching itself can be an independent factor contributing to HT of HSPKTR." - Anonymous Online Contributor

Unverified Answer

What are the common side effects of belatacept?

"A high risk of serious adverse events does not exist in belatacept-treated patients. All AEs reported herein were of grade 1 or grade 2. No AEs or deaths were considered to be drug-related. Recent findings has demonstrated the safety and tolerability of belatacept therapy when used to prevent rejection in high-risk kidney transplant recipients." - Anonymous Online Contributor

Unverified Answer

Have there been any new discoveries for treating highly sensitized prospective kidney transplant recipients?

"Current treatment of HSPRT includes triple immunosuppressive regimens and anti-CD154 agents without major differences in overall outcome. The use of anti-CD154 agents decreases the incidence of AR and acute rejection episodes, and thereby promotes long-term patient and graft survival." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
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