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

• Sponsor: First Affiliated Hospital of Zhejiang University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05913596
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 13.8
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Antibody-mediated Rejection; Kidney Tranplant	Drug: Daratumumab	N/A

Detailed 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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Each patient received CD38 monoclonal antibody monotherapyEach patient received CD38 monoclonal antibody monotherapy
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Prospective, One-arm Clinical Study
• Anticipated Study Start Date: Jul 8, 2023
• Anticipated Primary Completion Date: Apr 30, 2024
• Anticipated Study Completion Date: Aug 30, 2024

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Patient with CaAMR 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; 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.; Other Names: CD38 monoclonal antibody

Outcome Measures

Primary Outcome Measures

1. The change of donor specific antibody [6 months]

   Donor specific antibody changed 30% based on luminex HLA testing

Secondary Outcome Measures

1. The change of serum creatinine [6 months]

   Creatinine changed by 30% compared to before treatment or returned to baseline level

2. The change of BANFF score [6 months]

   The change of BANFF score, including c, g, ptc score

3. Incidence of treatment-related adverse events [6 months]

   Adverse event monitoring, assessment of labs, monitoring of viral PCRs

4. The change of NK cell count in PBMC [6 months]

   The change of NK cell count in PBMC collected at multiple time points throughout the study

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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 appropriate contraceptive measures

4. ABO incompatibility transplantation

5. Kidney transplantation biopsy combined with one of the following results:

1. T-cell mediated rejection B. New or recurrent severe thrombotic microangiopathy C. Polyomavirus nephropathy

1. Receive anti acute rejection treatment within 3 months before screening

2. 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

3. Total bilirubin>2 times the upper normal limit, alanine aminotransferase and aspartate aminotransferase>2.5 times the upper normal limit

4. Hemoglobin<8 g/dL

5. Thrombocytopenia: Platelets<100 × 109/L

6. Leukopenia: White blood cells<3 × 109/L, neutropenia: neutrophils<1.5 × 109/L

7. Hypogammaglobulinemia: Serum IgG<400 mg/dL

8. Eliminate active viral, bacterial, or fungal infections

9. Excluding Active Malignant Diseases with Intensive Immunosuppressive Therapy

10. Latent or active tuberculosis

11. Inoculate live vaccine within 6 weeks after screening

12. History of alcohol or illicit drug abuse

13. Serious medical or mental illness that may affect participation in the study

14. Active hepatitis B virus infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	79# Qingchun Road	Hangzhou	Zhejiang	China	310003

Sponsors and Collaborators

• First Affiliated Hospital of Zhejiang University

Investigators

• Principal Investigator: Jianyong Wu, MD, the First Affiliated Hospital of Medicine College, Zhejiang University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: First Affiliated Hospital of Zhejiang University
• ClinicalTrials.gov Identifier: NCT05913596
• Other Study ID Numbers: IIT20220103C-R1
• First Posted: Jun 22, 2023
• Last Update Posted: Jun 22, 2023
• Last Verified: Mar 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Daratumumab

Study Results

No Results Posted as of Jun 22, 2023