NCT06918990

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of carfilzomib and belatacept, administered with steroids and maintenance immunosuppression, in kidney transplant recipients with donor-specific antibody (DSA)-associated graft injury. Participants will be followed for 52 weeks after starting investigational therapy, including protocol biopsies at 3 months and 12 months after start of investigational therapy. The study will also assess changes in immune cell responses, blood and urine biomarkers, and biopsy-based pathomic features associated with antibody-mediated graft injury.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at P25-P50 for phase_1

Timeline
11mo left

Started May 2026

Geographic Reach
1 country

10 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress18%
May 2026Jun 2027

First Submitted

Initial submission to the registry

April 2, 2025

Completed
7 days until next milestone

First Posted

Study publicly available on registry

April 9, 2025

Completed
1.1 years until next milestone

Study Start

First participant enrolled

May 29, 2026

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2027

Last Updated

May 26, 2026

Status Verified

May 1, 2026

Enrollment Period

1.1 years

First QC Date

April 2, 2025

Last Update Submit

May 22, 2026

Conditions

Kidney Transplant Rejection

Keywords

CarfilzomibKidney transplantBelatacept

Outcome Measures

Primary Outcomes (2)

  • Proportion of subjects who do not meet a stopping rule for safety and remain free of all of the following: Grade 3 or higher infusion reaction, Grade 3 or higher infections, and any malignancy excluding localized non-melanomatous skin cancer.

    3-months post randomization and 12-months post receipt of Investigational Therapy (IT)

  • Proportion of subjects achieving either (1) ≥50% reduction in MFI or clearance below positivity threshold of immunodominant DSA, or (2) >20% improvement in 12-month post-treatment eGFR slope vs pre-enrollment

    Mean fluorescent intensity (MFI), donor-specific antibody (DSA), and estimated glomerular filtration rate (eGFR). The endpoint is the proportion of subjects achieving either: 1. 50% reduction in mean fluorescent intensity (MFI) or elimination below threshold for positivity of the immunodominant donor-specific antibody (DSA), or 2. improvement in 12-month post-treatment estimated glomerular filtration rate (eGFR) slope of greater than 20% compared with pre-enrollment eGFR slope

    3-months post randomization and 12-months post receipt of IT

Secondary Outcomes (15)

  • Change in albuminuria

    3-months post randomization and 12-months post receipt of IT

  • Change in Banff lesion grading score (2022 criteria)

    3-months post randomization and 12-months post receipt of IT

  • Change in immunodominant donor-specific antibody (DSA) MFI

    3-months post randomization and 12-months post receipt of IT

  • Change in estimated Glomerular Filtration Rate (eGFR) (2022 criteria)

    3-months post randomization and 12-months post receipt of IT

  • Incidence of Antibody-Mediated Rejection (ABMR)

    3-months post randomization and 12-months post receipt of IT

  • +10 more secondary outcomes

Study Arms (1)

Investigational Treatment Arm

EXPERIMENTAL

Study Entry to Month-3 participants will receive: * Steroid pulse/taper * Kyprolis® (Carfilzomib) * Nulojix® (Belatacept) * Tacrolimus * Mycophenolate * Prednisone After 3 months participants will receive: * Belatacept + * Mycophenolate * Prednisone * Tacrolimus

Biological: CarfilzomibBiological: Belatacept

Interventions

CarfilzomibBIOLOGICAL

Administered by intravenous infusion over 60 minutes.

Also known as: Kyprolis
Investigational Treatment Arm
BelataceptBIOLOGICAL

Administered by intravenous infusion over 30 minutes.

Also known as: Nulojix
Investigational Treatment Arm

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Able to understand and agree to participate in the study.
  • Have received a kidney transplant from a living or deceased donor (including re-transplants).
  • Men and women must agree to use birth control during the study and for 3 months after the last dose of study drugs, or be surgically sterile or post-menopausal.
  • Heart function must be good enough (LVEF of at least 40%) without severe heart issues or high blood pressure in the lungs.
  • Must have been previously exposed to the Epstein-Barr Virus (EBV).
  • Diagnosed with specific types of kidney transplant rejection based on criteria, with certain conditions on timing and treatment history.
  • Kidney function must be at a certain level (eGFR of at least 30 ml/min/1.73 m²).
  • Specific scores related to kidney biopsy results must be within certain limits.
  • Patient is ≥6-months post-transplant or is \<6 months post-transplant but has documentation that they have been offered and/or received the local standard of care treatment prior to enrollment.
  • Must have a measurable level of specific antibodies against the donor kidney (HLA DSA) with a certain intensity.
  • Up-to-date vaccinations according to guidelines for transplant patients.
  • Must have a negative tuberculosis (TB) test and chest x-ray before enrollment, no symptoms or known contact with TB, and not have recently traveled to or lived in areas with high TB rates. If previously infected with TB, must have completed treatment and have a recent negative chest x-ray.
  • If previously infected with COVID-19, must be fully recovered for at least 21 days before joining the study. No COVID-19 test required for those without symptoms.

You may not qualify if:

  • Unable or unwilling to give consent or follow study rules.
  • Kidney transplant with incompatible blood types.
  • Very high levels of protein in urine, indicating severe kidney issues.
  • Previously had a non-kidney organ or bone marrow transplant.
  • Any other medical issues that might increase risk, make following the study rules hard, or affect study results, as judged by the study doctor.
  • Heart attack within the last year, uncontrolled chest pain, or signs of a recent heart problem on an ECG.
  • Severe heart failure (Class 3 or higher).
  • Irregular heartbeats that can't be controlled with medication.
  • Participants who are actively receiving any of the therapies listed below, or who have previously received these therapies without meeting the required washout period prior to the qualifying biopsy and donor-specific antibody (DSA) assessment:
  • ≥4 weeks since last dose: IVIG (intravenous immunoglobulin), therapeutic plasma exchange (TPE)
  • ≥6 weeks since last dose: Proteasome inhibitors
  • ≥3 months since last dose: Eculizumab; lymphocyte-depleting agents (e.g., rabbit anti-thymocyte globulin, alemtuzumab); anti-CD20 agents
  • ≥6 months since last dose: Anti-CD38 agents; anti-IL-6 agents
  • Used any experimental drug not specified within the last 4 weeks or longer if the drug stays in the body longer.
  • Serious medical or mental health issues that could interfere with the study.
  • +18 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

University of Alabama Medical Center

Birmingham, Alabama, 35294, United States

NOT YET RECRUITING

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

NOT YET RECRUITING

UCLA Medical Center (Site #: 71123)

Los Angeles, California, 90024, United States

NOT YET RECRUITING

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

Washington University

St Louis, Missouri, 63110, United States

NOT YET RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Duke University

Durham, North Carolina, 27710, United States

NOT YET RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45267, United States

NOT YET RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

University of Wisconsin - Madison

Madison, Wisconsin, 53726, United States

NOT YET RECRUITING

Related Links

MeSH Terms

Interventions

carfilzomibAbatacept

Intervention Hierarchy (Ancestors)

ImmunoconjugatesAntibodiesImmunoglobulinsSerum GlobulinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsGlobulins

Study Officials

  • Stuart J Knechtle, M.D.

    Duke University Medical Center: Transplantation

    PRINCIPAL INVESTIGATOR

  • Scott Sanoff, MD, Ph.D.

    Duke University Medical Center: Transplantation

    STUDY CHAIR

Central Study Contacts

Yvonne Morrison, MS

CONTACT

301-706-9137ymorrison@niaid.nih.gov

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 2, 2025

First Posted

April 9, 2025

Study Start

May 29, 2026

Primary Completion (Estimated)

June 30, 2027

Study Completion (Estimated)

June 30, 2027

Last Updated

May 26, 2026

Record last verified: 2026-05

Locations

US(10)