Using daratumumab and belatacept to help highly sensitized kidney transplant candidates

A Mechanistically Driven Therapy to Desensitize >98.0% cPRA Patients: Depletion of Plasma Cells With Anti-CD38 and Prevention of B Cell Activation With Costimulation Blockade (ITN090ST)

This study is testing if a combination of two medications can help highly sensitized kidney transplant candidates find compatible donors faster.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Drugs / interventions: daratumumab
• Locations: 1 site (San Francisco, California)
• Trial ID: NCT04827979 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of daratumumab and belatacept in desensitizing highly sensitized kidney transplant candidates, who face long wait times for compatible donors. The study will enroll 15 adult participants with end-stage renal disease on dialysis, specifically those with calculated panel reactive antibodies (cPRA) ≥99.9% or >98% with extended waiting times. Participants will receive infusions of the two drugs over a 10 to 14-week period, followed by a 42-week follow-up to assess safety and efficacy. The goal is to lower the immune system's sensitization to kidney donors, potentially facilitating quicker access to suitable transplants.

Who should consider this trial

Good fit: Ideal candidates are adults with end-stage renal disease on dialysis and a cPRA of ≥99.9% or >98% with prolonged waiting times.

Not a fit: Patients who are not highly sensitized or those who do not meet the specific cPRA criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce wait times for kidney transplants in highly sensitized patients.

How similar studies have performed: While the approach of using these specific drugs for desensitization is novel, similar desensitization strategies have shown promise in other studies.

Eligibility 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 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

   --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 then documentation of two consecutive negative HCV quantitative ribonucleic acid (RNA) Polymerase chain reaction (PCR) tests separated by at least 6 months is required. Untreated subjects with HCV RNA are eligible.
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

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

Where this trial is running

San Francisco, California

• University of California at San Francisco Medical Center — San Francisco, California, United States (Recruiting)

Conditions Highly Sensitized Prospective Kidney Transplant Recipients; calculated panel reactive antibodies; desensitization therapy; human leukocyte antigen desensitization