The Safety and Efficacy of CD38 Monoclonal Antibody Monotherapy for CaAMR in Renal Transplantation

Last updated: September 13, 2023
Sponsor: First Affiliated Hospital of Zhejiang University
Overall Status: Active - Recruiting

Phase

N/A

Condition

Nephritis

Transplant Rejection

Treatment

Daratumumab

Clinical Study ID

NCT05913596
IIT20220103C-R1
  • Ages 18-80
  • All Genders

Study Summary

Renal transplantation is the best choice for the treatment of end-stage renal disease, but the long-term survival of the graft is still remains a challenge. Chronic antibody-mediated rejection (AMR) is the main factor affecting the long-term survival of the graft. There is still no effective treatment for chronic antibody-mediated rejection, even in the active phase (CaAMR). In recent years, new therapeutic drugs based on the generation of DSA and the mechanism of AMR, including protease inhibitor bortezomi, CD20 monoclonal antibody, C5 monoclonal antibody and IL-6 antibody, have not been able to effectively eliminate and inhibit the generation of DSA, nor have they been proved to have a definite effect on AMR.

CD38 is a type II transmembrane protein that is highly expressed on plasma cells and NK cells, which are considered to play a key role in the occurrence and development of AMR. Recently, a few cases have reported that CD38 monoclonal antibody combined plasma exchange and/or IVIG may be an effective strategy for the prevention and treatment of AMR, but the effectiveness and safety of daratumumab monotherapy on CaAMR were unknown. This is a multicenter, prospective, single arm clinical study. The study will enroll 15 renal transplant recipients with positive DSA and CaAMR confirmed by biopsy after renal transplantation. According to inclusion and exclusion criteria patients will be screened to participate in the trial.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Voluntary signing of written informed consent
  2. Age ≥ 18 years old
  3. ≥ 180 days after living donor kidney or DD donor kidney transplantation
  4. EGFR ≥ 30mL/min/1.73 m2 (CKD-EPI formula)
  5. Pre stored and/or newborn DSA (HLA antibody)

Exclusion

Exclusion Criteria:

  1. Patients participating in another clinical trial
  2. Age less than 18 years old
  3. Female subjects are pregnant or breastfeeding, or do not receive appropriatecontraceptive measures
  4. ABO incompatibility transplantation
  5. Kidney transplantation biopsy combined with one of the following results: A. T-cell mediated rejection B. New or recurrent severe thrombotic microangiopathy C.Polyomavirus nephropathy
  6. Receive anti acute rejection treatment within 3 months before screening
  7. Have been treated with other immunomodulatory monoclonal/polyclonal antibodies (suchas CD20 antibody, bortezomib, C5 monoclonal antibody, IL-6/IL-6R antibody) within 3months
  8. Total bilirubin>2 times the upper normal limit, alanine aminotransferase and aspartateaminotransferase>2.5 times the upper normal limit
  9. Hemoglobin<8 g/dL
  10. Thrombocytopenia: Platelets<100 × 109/L
  11. Leukopenia: White blood cells<3 × 109/L, neutropenia: neutrophils<1.5 × 109/L
  12. Hypogammaglobulinemia: Serum IgG<400 mg/dL
  13. Eliminate active viral, bacterial, or fungal infections
  14. Excluding Active Malignant Diseases with Intensive Immunosuppressive Therapy
  15. Latent or active tuberculosis
  16. Inoculate live vaccine within 6 weeks after screening
  17. History of alcohol or illicit drug abuse
  18. Serious medical or mental illness that may affect participation in the study
  19. Active hepatitis B virus infection

Study Design

Total Participants: 15
Treatment Group(s): 1
Primary Treatment: Daratumumab
Phase:
Study Start date:
May 23, 2023
Estimated Completion Date:
August 30, 2024

Study Description

After successful enrollment, the patient will receive daratumumab of 16mg/kg once every two weeks (0-22 weeks) for a total of 12 times, and continue to receive triple immunosuppressive therapy with prednisone, mycophenolic acid, tacrolimus (target valley concentration of 5-7ng/ml) or cyclosporine (target valley concentration of 100-200ng/ml). Peripheral blood samples were collected from 0 to 24 weeks (weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24) for routine blood tests, liver and kidney function electrolytes, tacrolimus or cyclosporine trough concentrations, HLA antibody quantification (weeks 0, 4, 8, 12, 16, 20, and 24), infection indicators (weeks 0, 8, and 24), immune status assessments (weeks 0, 4, 8, 12, 16, 20, and 24), and biopsy of transplanted kidneys was performed at 24 weeks to assess pathological changes.

Connect with a study center

  • 79# Qingchun Road

    Hangzhou, Zhejiang 310003
    China

    Active - Recruiting

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