IVIG/Rituximab vs Rituximab in Kidney Transplant With de Novo Donor-specific Antibodies

A Randomized, Open, Controlled Trial of High Dose IVIG/Rituximab Versus Rituximab in Kidney Transplant Patients With de Novo Donor-specific Antibodies

The objective of this study was to compare two strategies of de novo donor specific antibodies (DSA) and antibody-mediated rejection (AMR) prevention in renal transplant recipients: high dose intravenous immunoglobulin (IVIG)/rituximab regimens versus rituximab alone.

Study Overview

• Status: Completed
• Conditions: Renal Transplant
• Intervention / Treatment: Drug: Rituximab; Drug: intravenous immune globulin

Detailed Description

Although recent advances in immunosuppressive regimens after kidney transplantation (KT) have reduced the incidence and consequences of T-cell-mediated rejection (TCMR) and have improved short-term outcomes, long-term allograft loss attributable to AMR is still responsible for substantial medical and socioeconomic burdens in kidney transplant recipients. Numerous studies have shown that de novo DSA after KT are associated with AMR, which leads to allograft loss. IVIG is a medication that has emerged as a useful tool in modulating immunity, treatment of AMR and in desensitization protocol. Treatment with rituximab or combination of IVIG/rituximab has sought to further diminish antibody production (de novo DSA) in the treatment of AMR. Several studies have been reported, but in the absence of control groups or standardization of treatment, their efficacy is difficult to assess.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All patients have de novo production of DR or DQ DSA after renal transplantation Inclusion criteria requires all of the following

1. age ≥ 19 years
2. Renal transplants with eGFR ≥ 20 ml/min (by CKD-EPI equation) and change in the eGFR ≤ 20 within 3 months
3. No history of biopsy proven acute T cell mediated rejection or antibody-mediated rejection within 3 months
4. peak MFI of de novo DSA (DR or DQ) ≥ 1000
5. A patient who agree to write a written consent form

Exclusion Criteria:

1. age ≤ 18 years
2. multi-organ transplantation
3. Patients with no history of tacrolimus as immunosuppressants
4. history of allergic or anaphylactic reaction to rituximab
5. human immunodeficiency virus infection
6. active infection
7. pregnancy or lactation
8. history of drug abuse or alcohol abuse within 6 months
9. history of malignancy within 5 years
10. history of treatment for psychiatric problems
11. hematologic or biochemical abnormalities (Hb < 7g/dL, Platelet < 1x105/mm3, AST/ALT > 80IU)
12. A patient who do not want to participate in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rituximab; Inj Rituximab 375mg/m2 IV given on day 0	Drug: Rituximab; IV rituximab; Other Names: mabthera
Active Comparator: Combination of high-dose IVIG and Rituximab; IV Rituximab 375mg/m2 on day 0 and IV high-dose IVIG 2g/kg on day 0	Drug: Rituximab; IV rituximab; Other Names: mabthera; Drug: intravenous immune globulin; iv intravenous immune globulin; Other Names: IVIG-SN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in delta DSA MFI sum	change of pre- and post-treatment DSA MFI sum, monitoring DSA during follow-up period	baseline and 3 months post-treatment, 1 year post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in estimated glomerular filtration rate(eGFR) by CKD-EPI equation	change of pre- and post-treatment eGFR by CKD-EPI equation, monitoring eGFR during follow-up period	baseline and 3 months post-treatment, 1 year post-treatment
Development of antibody-mediated rejection (AMR)	To identify the development of AMR after treatment during follow-up period	up to 1 year post-treatment

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: GC Biopharma Corp; Severance Hospital
• Investigators: Principal Investigator: Jaeseok Yang, M.D., Ph.D., Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2019
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): May 3, 2022

Study Registration Dates

• First Submitted: July 24, 2019
• First Submitted That Met QC Criteria: July 24, 2019
• First Posted (Actual): July 26, 2019

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; Rituximab; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 20180138795

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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.: Yes