Daratumumab and Belatacept for Desensitization

Eligibility Criteria

• 1. Subject must be able to understand and provide informed consent
• 2. End stage renal disease (ESRD) on dialysis
• 3. United Network for Organ Sharing (UNOS) listed listed with current calculated panel reactive antibodies (cPRA) ≥99.9% or \>98% (with \>5 years of waiting time) awaiting deceased donor transplant
• 4. Evidence of established immunity to Epstein-Barr Virus (EBV) as demonstrated by serologic testing
• 5. Negative result of most recent tuberculosis (TB) testing or appropriately completed latent TB infection (LTBI) therapy.
• * Testing should be conducted using either a PPD or interferon-gamma release assay (i.e., QuantiFERON-TB, T-SPOT.TB)
• * Results from tests performed within 12 months prior to study entry are acceptable in the absence of any intervening exposure to TB
• * Subjects with a positive test for LTBI must complete appropriate therapy for LTBI ---LTBI treatment regimens should be among those endorsed by the Centers for
• 6. Negative Food and Drug Administration (FDA)-approved test for human immunodeficiency virus (HIV) diagnosis (at screening or as documented in medical record, up to 12 months prior to screening)
• 7. Negative Hepatitis C antibody test at screening or as documented in medical record, up to 12 months prior to screening
• 8. Negative result for SARS-CoV-2 by an FDA-authorized molecular diagnostic test. Examples include, but are not limited to RT-PCR, LAMP, TMA, and qSTAR.
• 9. Female subjects of reproductive potential must have a negative pregnancy test upon study entry
• 10. All subjects of reproductive potential must agree to use of contraception for the duration of the study
• 11. Subjects must have current vaccinations or documented immunity to varicella, measles, hepatitis B, pneumococcus, influenza, and zoster (if ≥50 years old)
• * If subjects require administration of vaccines to meet eligibility requirements, they must wait at least 2 weeks between vaccination and the baseline (Visit 0) visit
• 1. Inability or unwillingness of a subject to give written informed consent or comply with study protocol
• 2. Known active current or history of invasive fungal infection or non-tuberculous mycobacterial infection
• 3. Hepatitis B surface antigen or core antibody positive
• 4. Serious uncontrolled concomitant major organ disease excluding kidney failure
• 5. Previous non-kidney solid organ or bone marrow transplant
• 6. Any infection requiring hospitalization and intravenous (IV) antibiotics within 4 weeks of screening or by mouth (PO) antibiotics within 2 weeks
• 7. Primary or secondary immunodeficiency
• 8. History of active tuberculosis (TB), even if treated
• 9. History of positive result for 2019-novel Coronavirus (2019-nCoV) by real-time reverse transcriptase (RT-PCR)
• 10. Malignancy within the last 5 years except treated basal and squamous cell cancer of the skin or treated in situ cervical cancer
• 11. History of plasma cell dyscrasia
• 12. Alcohol, drug, or chemical abuse within 1 year
• 13. Difficult peripheral venous access
• 14. Need for uninterrupted anticoagulation
• 15. Neutropenia (absolute neutrophil count \<1000/uL) or thrombocytopenia (platelet count \<100,000/uL) within 4 weeks prior to study enrollment
• 16. Women who are currently pregnant or nursing
• 17. Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening
• 18. Current treatment with other biological drug
• 19. Immunization with live vaccine within 2 weeks of study baseline (Visit 0) visit
• 20. Past or current medical problems or findings from physical examination or laboratory testing not listed above, which, in the opinion of the investigator, may:
• * pose additional risks from participation in the study,
• * interfere with the subject's ability to comply with study requirements, or
• * impact the quality or interpretation of the data obtained from the study