Treatment of Antibody-Mediated Rejection (ABMR) With CarBel

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Begins enrollment in 1 month; Phase 2

Conditions: Kidney Transplant Rejection

Treatments: Biological: Carfilzomib; Biological: Belatacept

Study type: Interventional

Funder types: NIH

Identifiers

NCT06918990

DAIT CTOT-42

Details and patient eligibility

About

The purpose of this study is to see:

1. If using these two drugs (carfilzomib and belatacept) together is safe
2. If the use of these two study drugs in addition to the usual immunosuppression for kidney transplant patients can improve your transplanted kidney function by lowering the antibodies you have against your transplanted kidney
3. If the study drugs effect the immune cells that were responding to your donor kidney. And, whether blood or urine tests can measure signs of inflammation and kidney cell injury
4. If using new computer techniques can help describe important changes seen on biopsy in your donated kidneys

The primary objective is to assess the efficacy of carfilzomib and belatacept therapy when added to current treatment with steroids and maintenance immunosuppression, compared to conventional treatment alone, to improve the clinical outcome of renal transplant patients with active and chronic - active ABMR occurring more than 6 months after renal transplantation or less than 6 months post-transplant with persistent refractory Antibody-Mediated Rejection (ABMR)

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Able to understand and agree to participate in the study.
2. Have received a kidney transplant from a living or deceased donor (including re-transplants).
3. 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.
4. Heart function must be good enough (LVEF of at least 40%) without severe heart issues or high blood pressure in the lungs.
5. Must have been previously exposed to the Epstein-Barr Virus (EBV).
6. Diagnosed with specific types of kidney transplant rejection based on criteria, with certain conditions on timing and treatment history.
7. Kidney function must be at a certain level (eGFR of at least 30 ml/min/1.73 m²).
8. Specific scores related to kidney biopsy results must be within certain limits.
9. Must have a measurable level of specific antibodies against the donor kidney (HLA DSA) with a certain intensity.
10. Up-to-date vaccinations according to guidelines for transplant patients.
11. 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.
12. 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.

Exclusion criteria

1. Unable or unwilling to give consent or follow study rules.
2. Kidney transplant with incompatible blood types.
3. Very high levels of protein in urine, indicating severe kidney issues.
4. Previously had a non-kidney organ or bone marrow transplant.
5. Any other medical issues that might increase risk, make following the study rules hard, or affect study results, as judged by the study doctor.
6. Heart attack within the last year, uncontrolled chest pain, or signs of a recent heart problem on an ECG.
7. Severe heart failure (Class 3 or higher).
8. Irregular heartbeats that can't be controlled with medication.
9. Used any experimental drug within the last 4 weeks or longer if the drug stays in the body longer.
10. Serious medical or mental health issues that could interfere with the study.
11. Cancer diagnosis or treatment within the past 2 years, except for certain skin cancers or cancers with a high cure rate.
12. Known allergy to Captisol® (used in the study drug).
13. Very low blood counts (hemoglobin, neutrophils, or platelets).
14. Positive for HIV, Hepatitis B, or Hepatitis C, unless Hepatitis C was successfully treated.
15. Severe infections needing treatment in the last 4 weeks.
16. Specific kidney infection (BK nephropathy) or high levels of BK virus.
17. Certain kidney biopsy results indicating other types of rejection or kidney diseases.
18. Treated for a specific viral infection (CMV) in the last 90 days or resistant to certain CMV treatments.
19. Received a live vaccine in the last 4 weeks.
20. Severe liver disease or abnormal liver tests.
21. Pregnant or breastfeeding women. Women who can become pregnant must have a negative pregnancy test or proof they are not pregnant.
22. Any other significant medical condition that could interfere with the study according to the doctor.
23. Received certain antibody treatments in the last 3 months.
24. Kidney rejection within 6 months post-transplant without standard care.
25. Confirmed severe protein levels in urine.
26. Underwent certain treatments outside study criteria.
27. History of multiple unprovoked blood clots.
28. Diagnosed with Atypical Hemolytic Uremic Syndrome (aHUS).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Investigational Treatment Arm

Experimental group

Description:

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

Treatment:

Biological: Belatacept

Biological: Carfilzomib

Conventional Treatment Arm

Experimental group

Description:

Study Entry to Month-3 participants will receive: * Steroid pulse/taper * Intravenous Immunoglobulin (IVIG) * Tacrolimus OR Belatacept + * Mycophenolate * Prednisone After 3 months participants will receive: * Kyprolis® (Carfilzomib) * Nulojix ® (Belatacept) * Tacrolimus * Mycophenolate * Prednisone After an additional 3 months (6 months from study entry) participants will receive: * Belatacept + * Mycophenolate * Prednisone * Tacrolimus

Treatment:

Biological: Belatacept

Biological: Carfilzomib