Intravenous Immunoglobulins for Prevention of BKV Infection in Kidney Transplant Recipients According to BKV Genotype-specific Neutralizing Antibody Titers at the Day of Transplantation. (BKANIG)

Intravenous Immunoglobulins for Prevention of BKV Infection in Kidney Transplant Recipients According to BKV Genotype-specific Neutralizing Antibody Titers at the Day of Transplantation: A Multicenter Study

BK virus-associated nephropathy (BKVAN), a consequence of the strong immunosuppressive therapy given after kidney transplantation (KT), represents a growing medical problem in the KT setting. BKV replication occurs in 30-50% of recipients with progression to BKVAN in up to 10% of patients which ultimately leads to graft dysfunction and loss. Furthermore, early BKV replication after transplantation increases the risk of late acute rejection. At present, there are no BKV-specific antiviral therapies available. The current management of BKVAN relies on preemptive adaptation of immunosuppression according to viral load monitoring. However, due to its delayed nature, this empirical strategy is not always successful, and can increase the risk of donor specific antibodies, graft rejection and death. In a prospective longitudinal study, the investigators have demonstrated that the amount and kinetics of BKV genotype-specific neutralizing antibody (NAb) titers influence BKV disease severity after KT; and defined a cutoff NAb titer value of 4 log10 that allows stratification of recipients into lower and higher BKV disease risk groups prior to KT. Furthermore, our data on donor/recipient pairs provide support for the view reported by recent studies that early BKV replication in kidney transplant recipients is of donor origin. These data support the potential benefit of administering NAbs as a preventive strategy against BKV infection. The investigators and others have demonstrated the presence of high titers of BKV NAbs in commercial intravenous immunoglobulins (IVIG). The investigators further evaluated the titer of BKV NAbs in plasma samples of transplant recipients after administration of IVIG. The investigators demonstrated that all patients show an increase of NAb titers in plasma after IVIG administration. The aim of the investigators study is to investigate the efficacy of IVIG for prevention of BKV viremia after KT according to pre-transplant BKV genotype-specific NAb titers against the donor's BKV strain. The study is a multicentric prospective randomized open trial evaluating the impact of administration of IVIG for prevention of BKV viremia compared to no specific treatment in kidney transplant recipients harboring neutralizing antibody titers (NAbs) ≤ 4log10 against the BKV donor's genotype. Recipients harboring BKV NAb titer ≤ 4log10 against the BKV genotype of their matched donor and negative or non-detectable BKV load in blood at day of transplantation will be randomized to receive (experimental group) or not (control group) IVIG treatment. In the experimental group, patients will receive a single dose of IVIG at day 10+/- 4 days, day 41 +/- 7 days and day 62 +/- 7 days. The dose of IVIG is defined according the donor BKV genotype: genotype I: 0.4 g/Kg/day; genotype II and IV: 1g/kg/day.

The incidence of BKV viremia (> 4 log10 copies/mL) 6 months after transplantation will be evaluated and compared between the two groups.

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Intravenous immunoglobulins (IVIG)

• Study Type: Interventional
• Enrollment (Estimated): 664
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Samira Fafi-Kremer; Phone Number: 03 69 55 14 38; Email: samira.fafi-kremer@chru-strasbourg.fr

Study Locations

• France
  • Strasbourg, France, 67000
    • Recruiting
    • Les Hôpitaux Universitaires de Strasbourg
    • Contact: Sophie Ohlmann- Caillard; Phone Number: 0388116768; Email: sophie.ohlmann@chru-strasbourg.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Adult patients (> 18 years)
• Kidney transplant recipients, including multiple organ transplant patients
• Patients able to understand the purpose and the risks of the study, fully informed and having written informed consent
• Negative pregnancy test
• Affiliated to a medical insurance scheme

Exclusion criteria:

• BKV nephropathy during a previous transplantation in the past 5 years
• HLA and ABO-incompatible kidney transplant recipients undergoing desensitization with rituximab and/or plasmapheresis before transplantation or susceptible to receive such therapy after transplantation
• Patients with high risk of post- transplant Focal Segmental glomerulosclerosis recurrence
• Patient with hyperprolinemia
• Allergy or known intolerance to IVIG
• Pregnant or breast feeding women
• Adults under guardianship or limited guardianship
• Currently participating in another clinical trial investigating drugs (observational studies are not considered as an exclusion criterion)

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
No Intervention: Control group
Experimental: IVIG group; Administration of a single dose of IVIG at day 10+/- 4 days, day 41 +/- 7 days and day 62 +/- 7 days. The dose of IVIG is defined according the donor BKV genotype: genotype I: 0.4 g/Kg/day; genotype II and IV: 1g/kg/day.	Drug: Intravenous immunoglobulins (IVIG); Experimental group: administration of a single dose of IVIG at: Day 10+/- 4 days; Day 41 +/- 7 days; Day 62 +/- 7 days The dose of IVIG is defined according the donor BKV genotype: genotype I: 0.4 g/Kg/day; genotype II and IV: 1g/kg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of BKV viremia	BKV viremia will be measured at the day of transplantation at day 10
The incidence of BKV viremia	BKV viremia will be measured at the day of transplantation at day 41
The incidence of BKV viremia	BKV viremia will be measured at the day of transplantation at day 62
The incidence of BKV viremia	KV viremia will be measured at the day of transplantation at months 3
The incidence of BKV viremia	BKV viremia will be measured at the day of transplantation at months 6
The incidence of BKV viremia	BKV viremia will be measured at the day of transplantation at months 12

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: December 19, 2019
• First Submitted That Met QC Criteria: January 7, 2020
• First Posted (Actual): January 9, 2020

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 18, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 6997 (Duke legacy protocol number)

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