Multicenter randomized two arms study evaluating the efficacy of prophylactic Rituximab in EBV negative kidney transplant recipients on incidence of EBV primary infection and post-transplant lymphoproliferative disorders - REPLY

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Les Hopitaux Universitaires De Strasbourg

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

1 Dec 2021 → ongoing

Decision date (initial)

2024-07-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515075-36-00

EudraCT number

2020-000492-21

ClinicalTrials.gov

NCT04989491

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The main objective of our study is to evaluate the efficacy of early infusion of Rituximab in the prevention of EBV primary infection and post-transplant lymphoproliferative disorder (PTLD) occurrence in EBV negative kidney transplant recipients transplanted with an EBV positive donor.

Secondary objectives 1

1. -The occurrence of PTLD during the 5 post-transplant years -The occurrence of post-transplant EBV primary infection during the 5 post-transplant years -The kinetics of post-transplant EBV replication -The clinical presentation of EBV primary infection -The incidence of post-transplant EBV seroconversion during the 5 posttransplant years -The post-transplant immune reconstitution kinetics -The kidney allograft function and graft survival during the 5 posttransplant years -The recipient survival during the 5 post-transplant years -The tolerance of Rituximab -The incidence of opportunistic infections and malignancies during the 5 years after transplantation -The incidence of BK virus and Cytomegalovirus (CMV) infections posttransplantation - All the previous objectives in pediatric and adult sub-populations

Conditions and MedDRA coding

kidney transplantion -Epstein Barr virus

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Adult patients (age ≥18 years at transplantation)
2. Kidney and kidney pancreas simultaneous transplantation
3. EBV seronegative patients (IgG anti EBNA, IgG anti VCA and IgM anti VCA negative) (from 6 months before transplantation to the day of transplantation, included)
4. Pediatric patients > 2 years and <18 years at transplantation
5. Patient who have given written informed consent
6. Negative pregnancy test and use of contraception during all the study or during 12 months after the administration of rituximab in case of early discontinuation of study-EBV positive donor
7. EBV positif donnor

Exclusion criteria 10

1. Patient with known HBV active infection
2. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients
3. Active severe infection
4. Severe Immune deficiency
5. Pregnant or lactating women
6. Women of child bearing potential unless they are using an acceptable birth control methods
7. Patient under judicial protection or under guardianship
8. Patient currently participating in another clinical trial investigating drugs. Observational studies are not considered as an exclusion criterion
9. Any form of substance abuse, psychiatric disorder or condition, which, in the opinion of the investigator, is incompatible with the participation in the study
10. Unlikely to comply with the visits scheduled in the protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1 year incidence of a composite criteria: EBV primary infection assessed by a positive blood EBV viral load and/or EBV seroconversion ; and/or occurrence of a post-transplant lymphoproliferative disorder

Secondary endpoints 15

1. 1, 2, 3, 4 and 5 years incidence of PTLD after kidney transplantation
2. Incidence of primary EBV infection evaluated by EBV viremia (PCR blood test) at M1, M2, M3, M6, M12, M24, M36, M48, M60 and EBV seroconversion at M1, M3, M6, M12, M24, M36, M48, M60.
3. Delay of occurrence of primary EBV infection
4. Delay of occurrence of primary EBV infection
5. CD19/CD20 reconstitution at M3, M6, M12, M24
6. Number of patients with high EBV viral load who need Rituximab for preemptive therapy in each group
7. Graft loss at M1, M2, M3, M6, M12, M24, M36, M48, M60
8. Allograft kidney function evaluated by CKD-EPI formula or by Schwartz formula in pediatric patients at M1, M2, M3, M6, M12, M24, M36, M48, M60Recipient survival at M1, M2, M3, M6, M12, M24, M36, M48, M60
9. Incidence of opportunistic infections and malignancies at M1, M2, M3, M6, M12, M24, M36, M48, M60
10. Incidence of BKV viremia (PCR blood test) M1, M3, M6, M12 and M24
11. Delay of BKV viremia
12. Incidence of CMV viremia (PCR blood test) at M1, M3, M6, M12 and XML File Identifier: BMpUWXavs2G+LuOr9Bi86K8SCls= Page 12/29 M24
13. Treatment tolerance: allergic reaction, neutropenia, hospitalization for febrile neutropenia, hypogammaglobulinémia
14. AE/SAE
15. All these end points in specific pediatric and adult sub groups

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Les Hopitaux Universitaires De Strasbourg

Sponsor organisation

Les Hopitaux Universitaires De Strasbourg

Address

1 Place De L Hopital, Cs 80426 Cs 80426

City

Strasbourg Cedex

Postcode

67091

Country

France

Scientific contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Sophie CAILLARD

Public contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Sophie CAILLARD

Locations

1 EU/EEA country · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications