Daratumumab and Belatacept for Desensitization

• Status: Not yet recruiting
• Trial end date: 2023-04-01
• Target enrollment: 15
• Participant gender: All

Summary

This is a pilot, safety and efficacy trial of a combination of daratumumab and belatacept to achieve desensitization in prospective kidney transplant recipients with cPRA >95.0%. Eligible subjects will receive 6 infusions of daratumumab (8 mg/kg) and 4 infusions of belatacept (10 mg/kg) over 10 weeks. All subjects will undergo human leukocyte antigen (HLA) antibody assessments and bone marrow aspiration prior to and after completion of treatment, and receive 26 weeks of follow up after completing treatment. Subjects who receive a kidney transplant while in the study will receive protocol-directed immunosuppression and undergo additional 52 weeks of follow up.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Bristol-Myers Squibb; Immune Tolerance Network (ITN); PPD; Rho Federal Systems Division, Inc.
• Treatments: Abatacept; Daratumumab; Immunoglobulin G; Immunoglobulins

Criteria

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as study subjects-

1. Subject must be able to understand and provide informed consent

2. End stage renal disease (ESRD) on hemodialysis

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

--Note: Those with cPRA >98% with human leukocyte antigen (HLA)-incompatible approved living donor who have not received a transplant after 1 year in a paired kidney exchange program are also eligible

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

Disease Control and Prevention (CDC), Division of TB Elimination, url:

https://www.cdc.gov/tb/topic/treatment/ltbi.htm

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

--If there is a history of treated hepatitis C or there is a suspected false positive hepatitis C virus (HCV) antibody test, then documentation of two consecutive negative HCV quantitative ribonucleic acid (RNA) Polymerase chain reaction (PCR) tests separated by at least 6 months is required

8. Negative result for 2019-novel Coronavirus (2019-nCoV) by real-time reverse transcriptase (RT-PCR)

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

Exclusion Criteria:

Individuals who meet any of these criteria are not eligible for enrollment as study subjects-

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