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.

NCT07379957 | Not Yet Recruiting

• 1 other identifier: CHUBX2025/031
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 20

Brief Summary

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.

Conditions

Kidney Transplantation

Keywords

End-stage renal disease; kidney transplant rejection; recombinant cysteine protease derived from Streptococcus pyogenes; imlifidase

Outcome Measures

Primary Outcomes (1)

• Percentage of transplantations performed with or without imlifidase among the eligible patients

  CRISTAL register

  Year 1, year 2 and year 3 after kidney transplantation

Secondary Outcomes (8)

• Incidence of HLA donor-specific antibodies (DSA) rebound after transplantation

  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

  Days 3, 5, 7, 10, and month 1, month 3 and month 12, after kidney transplantation

• Incidence of antibody-mediated rejection

  Day 10, month 3 and month 12 after kidney tranplantation

• eGFR

  Days 7, 14, month 1, month 3 and month 12 after kidney transplantation

• Description of infection on post-transplantation

  Year 1, year 2 and year 3 after kidney transplantation

Study Arms (3)

Patient eligible for Imlifidase

Patient eligible for imlifidase and transplanted with

Patient eligible for imlifidase but transplanted without

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

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

You may not qualify if:

• Age \< 18 years-old

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (20)

CHU Amiens Picardie Site Sud

Amiens, 80000, France

Location

Hôpital de Bois-Guillaume

Bois-Guillaume, 76000, France

Location

Hôpital Pellegrin

Bordeaux, 33000, France

Location

CHU Caen Normandie

Caen, 14000, France

Location

Hôpital Henri Mondor

Créteil, 94000, France

Location

CHU de Grenoble Alpes

Grenoble, 38000, France

Location

Hôpital Huriez

Lille, 59000, France

Location

Hôpital Edouard Herriot

Lyon, 69000, France

Location

Hôpital de la Conception

Marseille, 13000, France

Location

CHU de Nantes

Nantes, 44000, France

Location

Hôpital Pasteur

Nice, 06000, France

Location

Hôpital Bicêtre

Paris, 75000, France

Location

Hôpital Necker

Paris, 75000, France

Location

Hôpital Saint-Louis

Paris, 75000, France

Location

CHU de Reims

Reims, 51000, France

Location

CHU Saint Etienne

Saint-Etienne, 42000, France

Location

CHU de Strasbourg

Strasbourg, 67000, France

Location

Hôpital Foch

Suresnes, 92000, France

Location

Hôpital Rangueil

Toulouse, 31000, France

Location

CHU Tours Bretonneau

Tours, 37000, France

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Lionel COUZI, Pr

CONTACT

05 56 79 55 38; lionel.couzi@chu-bordeaux.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 36 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2025
• First Posted: February 2, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: February 2, 2026

Record last verified: 2026-01

Locations

FR (20)