Imlifidase for Highly Sensitized Kidney Transplant Recipients With a posItive crossmAtch Against a Deceased Donor: Results of Kidney Transplantations Performed in Accordance to the French Guidelines. (ISKIA)

January 23, 2026 updated by: University Hospital, Bordeaux

Imlifidase is a recombinant cysteine protease derived from Streptococcus pyogenes and produced in Escherichia coli, which has the ability to cleave and degrade all human IgGs. Four to six hours after imlifidase infusion, the entire IgG pool is degraded into F(ab')2 and Fc fragments. In vitro, imlifidase inhibits HLA antibody-mediated NK cell activation and antibody-dependent cell-mediated cytotoxicity. Imlifidase degrades also the IgG of the B cell Receptor (BCR), inhibiting BCR-mediated cell signal, transiently preventing memory B cell response to antigenic stimulation and their transition into antibody-producing cells.

Two clinical studies have been designed to determine whether imlifidase could inactivate IgG donor-specific antibodies as a desensitization strategy in highly sensitized candidates for kidney transplantation. In the phase I/II study, 25 patients were transplanted in Sweden and United States. Among them, 18 had a positive flow cytometry crossmatch (FCXM) and 2 a positive complement-dependent cytotoxicity crossmatch (CDCXM). In the phase II study (Highdes Trial), 19 patients with an incompatible living or deceased donor from the United States, Sweden, and France were included. Among them, 7, 18, 2, and 8 had respectively a positive T-cell FCXM, positive B-cell FCXM, positive T-cell CDCXM, and positive B-cell CDCCXM. The primary efficacy endpoint was the ability of Imlifidase to convert a positive XM to a negative one. Conversion of baseline positive XM to negative within 24 h after Imlifidase treatment occurred in 89.5% (n=17) of the 19 patients. In the follow-up study including all the patients transplanted after Imlifidase desensitization, the antibody-mediated rejection rate (AMR) was at 39%, most of them occurring during the first month post-transplantation. Three-year death-censored graft survival was 93% in patients with AMR and 77% in the others. Three-year patient survival was 85% in patients with AMR and 94% in the others. No safety signal was reported.

Based on these data, Imlifidase is now indicated as a desensitization agent of highly sensitized adult kidney transplant patients with positive crossmatch against an available ABO-compatible deceased donor. It should be reserved for patients unlikely to be transplanted under the available kidney allocation system including the prioritization program for highly sensitized patients (https://www.ema.europa.eu). Therefore, the French Society of Transplantation (SFT), the French-speaking Society of Nephrology, Dialysis and Transplantation (SFNDT) and the French Society of Histocompatibility and Immunogenetics (SFHI) have proposed French recommendations for patient selection, choice of antibodies characteristics, treatment and follow-up in order to homogenize practices.

Although this new treatment addressed an unmet medical need, its authorization was based on only two small-scale studies. Therefore, additional data on long-term graft function and survival are required in patients treated by imlifidase.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. However, highly sensitized patients have a very difficult access to transplantation because of a very low number of compatible donors. Imlifidase is a major breakthrough in kidney transplantation, because it allows transplanting these highly sensitized patients considered as untransplantable until now. The findings coming from the ISKIA study will help to refine the use and implementation of imlifidase in this population.

The main objective of this retrospective study is to analyze the efficacy and safety of kidney transplantations performed with a positive crossmatch against a deceased donor, where imlifidase is used in accordance to the French guidelines.

The secondary objectives of the ISKIA study are:

  • To identify the characteristics and analyze the outcome of kidney recipients eligible to imlifidase but transplanted without imlifidase
  • To identify the characteristics of kidney recipients eligible to imlifidase but not transplanted

Study Type

Observational

Enrollment (Estimated)

450

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

When a kidney transplant candidate eligible to imlifidase is identified in a transplant center in France, HLA antibodies are delisted by the HLA laboratory, according to the French guidelines. Following this delisting, the patients can be transplanted with or without imlifidase or stay on dialysis.

Bordeaux University Hospital will establish agreements with the 20 other university hospitals who have patients eligible to imlifidase.

An implementation visit will be carried out at each CHU to:

  1. identify patients already eligible for imlifidase,
  2. set up a system to inform the Bordeaux CHU, as the coordinating center, when new incident patients eligible for imlifidase are identified,
  3. offer all identified patients' inclusion in the ISKIA study

Description

Inclusion Criteria:

  • Highly sensitized adult kidney transplant candidates
  • Eligible to imlifidase (patient with a delisting of at least one A, B, DR, DQ HLA antibody)

Exclusion Criteria:

  • Age < 18 years-old

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Patient eligible for Imlifidase
Patient eligible for imlifidase and transplanted with
Patient eligible for imlifidase but transplanted without

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of transplantations performed with or without imlifidase among the eligible patients
Time Frame: Year 1, year 2 and year 3 after kidney transplantation
CRISTAL register
Year 1, year 2 and year 3 after kidney transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of HLA donor-specific antibodies (DSA) rebound after transplantation
Time Frame: Days 3, 5, 7, 10, and month 1, month 3 and month 12, after kidney transplantation
DSA analysis on a Luminex platform
Days 3, 5, 7, 10, and month 1, month 3 and month 12, after kidney transplantation
Timing of HLA donor-specific antibodies (DSA) rebound after transplantation
Time Frame: Days 3, 5, 7, 10, and month 1, month 3 and month 12, after kidney transplantation
DSA analysis on a Luminex platform
Days 3, 5, 7, 10, and month 1, month 3 and month 12, after kidney transplantation
Incidence of antibody-mediated rejection
Time Frame: Day 10, month 3 and month 12 after kidney tranplantation
Protocol and indication biopsies
Day 10, month 3 and month 12 after kidney tranplantation
eGFR
Time Frame: Days 7, 14, month 1, month 3 and month 12 after kidney transplantation
Estimated eGFD based on serum creatinine (CKD-epi formula)
Days 7, 14, month 1, month 3 and month 12 after kidney transplantation
Description of infection on post-transplantation
Time Frame: Year 1, year 2 and year 3 after kidney transplantation
Collection of events on patients' records
Year 1, year 2 and year 3 after kidney transplantation
Description of cancer post-transplantation
Time Frame: Year 1, year 2 and year 3 after kidney transplantation
Collection of events on patients' records concerning cancer onset post-transplantation
Year 1, year 2 and year 3 after kidney transplantation
Patient and graft survivals
Time Frame: Year 1, year 2 and year 3 after kidney transplantation
Collection of events on patients' records concerning graft survivals
Year 1, year 2 and year 3 after kidney transplantation
Patients placed on the waiting list after transplantation
Time Frame: Year 1, year 2 and year 3 after kidney transplantation
Patients placed on the waiting list after transplantation will be estimated thanks to CRISTAL register
Year 1, year 2 and year 3 after kidney transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2026

Primary Completion (Estimated)

February 1, 2029

Study Completion (Estimated)

February 1, 2029

Study Registration Dates

First Submitted

September 26, 2025

First Submitted That Met QC Criteria

January 23, 2026

First Posted (Actual)

February 2, 2026

Study Record Updates

Last Update Posted (Actual)

February 2, 2026

Last Update Submitted That Met QC Criteria

January 23, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX2025/031

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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