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

NCT05913596 | Unknown

• 1 other identifier: IIT20220103C-R1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Antibody-mediated Rejection; Kidney Tranplant

Outcome Measures

Primary Outcomes (1)

• The change of donor specific antibody

  Donor specific antibody changed 30% based on luminex HLA testing

  6 months

Secondary Outcomes (4)

• The change of serum creatinine

  6 months

• The change of BANFF score

  6 months

• Incidence of treatment-related adverse events

  6 months

• The change of NK cell count in PBMC

  6 months

Study Arms (1)

Patient with CaAMR

EXPERIMENTAL

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.

Drug: Daratumumab

Interventions

Daratumumab DRUG

After successful enrollment, the patient will receive daratumumab of 16mg/kg once every two weeks (0-22 weeks) for a total of 12 times. 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.

Also known as: CD38 monoclonal antibody

Patient with CaAMR

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients participating in another clinical trial
• Age less than 18 years old
• Female subjects are pregnant or breastfeeding, or do not receive appropriate contraceptive measures
• ABO incompatibility transplantation
• 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
• Receive anti acute rejection treatment within 3 months before screening
• Have been treated with other immunomodulatory monoclonal/polyclonal antibodies (such as CD20 antibody, bortezomib, C5 monoclonal antibody, IL-6/IL-6R antibody) within 3 months
• Total bilirubin\>2 times the upper normal limit, alanine aminotransferase and aspartate aminotransferase\>2.5 times the upper normal limit
• Hemoglobin\<8 g/dL
• Thrombocytopenia: Platelets\<100 × 109/L
• Leukopenia: White blood cells\<3 × 109/L, neutropenia: neutrophils\<1.5 × 109/L
• Hypogammaglobulinemia: Serum IgG\<400 mg/dL
• Eliminate active viral, bacterial, or fungal infections
• Excluding Active Malignant Diseases with Intensive Immunosuppressive Therapy

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

79# Qingchun Road

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Interventions

daratumumab

Study Officials

• Jianyong Wu, MD

  the First Affiliated Hospital of Medicine College, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianyong Wu, MD

CONTACT

86-571-87236189; wujianyong1964@zju.edu.cn

Yu Cui, MD

CONTACT

86-571-87236992; cuiyu@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each patient received CD38 monoclonal antibody monotherapy

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: June 22, 2023
• Study Start: May 23, 2023
• Primary Completion: April 30, 2024
• Study Completion: August 30, 2024
• Last Updated: September 14, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 6 months after the end of the study
• Access Criteria: Contact the investigator to obtain via email

Locations

CN (1)