Imlifidase in Living Donor Renal Transplantation Highly Sensitized Recipients

NCT ID: NCT06461546

Last Updated: 2025-03-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-22
• Study Completion Date: 2027-05-31

Brief Summary

This is a Phase II, pilot, prospective, unicentric trial, to evaluate Imlifidase could improve the transplantability of the highly sensitized patients with good outcomes respect to survival and functionality of the graft.

Detailed Description

The patients between 18 and 65 years will be flow cytometry crossmatch (FC-XM) positive against an available living donor. The imlifidase treatment will turn the crossmatch test negative prior to transplantation. A second dose of imlifidase can be given within 24 hours if the first dose is considered not to have sufficient effect. If a second dose is given, a confirmatory FCXM test will be performed pre-second imlifidase dosing and between 2-6 hours following the second dose.

Conditions

Kidney Transplant Candidates

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imlifidase treatment

Single arm pilot study

All highly sensitized patients included in the study will receive the immunosuppressive standard of care therapy at Hospital Clínic de Barcelona and in addition the study drug:

• Imlifidase (POD0, pre-transplantation), imlifidase, 0.25 mg/kg over a period of 15 minutes, prior to transplantation.
• Dose Adjustment Criteria

FC-XM screening and single antigen will be performed after 6 hours of imlifidase infusion, It will take 3 hours to obtain the results, respectively:

• NEGATIVE (FC-XM) - renal transplantation will be performed as soon as possible.
• POSITIVE (FC-XM) - 2nd Imlifidase infusion will be required (imlifidase dose: 0.25mg/Kg).

FC-XM screening and single antigen will be performed after 2 hours of the 2nd Imlifidase infusion:

• NEGATIVE (FC-XM) - renal transplantation will be performed as soon as possible.
• POSITIVE (FC-XM) - The scheduled kidney transplant will be canceled.

Group Type: EXPERIMENTAL

Imlifidase

Intervention Type: DRUG

• Imlifidase (POD0, pre-transplantation), imlifidase, 0.25 mg/kg over a period of 15 minutes, prior to transplantation.
• Dose Adjustment Criteria

FC-XM screening and single antigen will be performed after 6 hours of imlifidase infusion, It will take 3 hours to obtain the results, respectively:

• NEGATIVE (FC-XM) - renal transplantation will be performed as soon as possible.
• POSITIVE (FC-XM) - 2nd Imlifidase infusion will be required (imlifidase dose: 0.25mg/Kg).

FC-XM screening and single antigen will be performed after 2 hours of the 2nd Imlifidase infusion:

• NEGATIVE (FC-XM) - renal transplantation will be performed as soon as possible.
• POSITIVE (FC-XM) - The scheduled kidney transplant will be canceled.

Interventions

Imlifidase

• Imlifidase (POD0, pre-transplantation), imlifidase, 0.25 mg/kg over a period of 15 minutes, prior to transplantation.
• Dose Adjustment Criteria

FC-XM screening and single antigen will be performed after 6 hours of imlifidase infusion, It will take 3 hours to obtain the results, respectively:

• NEGATIVE (FC-XM) - renal transplantation will be performed as soon as possible.
• POSITIVE (FC-XM) - 2nd Imlifidase infusion will be required (imlifidase dose: 0.25mg/Kg).

FC-XM screening and single antigen will be performed after 2 hours of the 2nd Imlifidase infusion:

• NEGATIVE (FC-XM) - renal transplantation will be performed as soon as possible.
• POSITIVE (FC-XM) - The scheduled kidney transplant will be canceled.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Sensitized (cPRA ≥ 50%) kidney transplant candidates between 18 and 65 years.
• Low probability to get a transplant in a kidney exchange program (KEP) from a living donor.
• Included in the living donor program, with an accepted potential living donor.
• Donor and recipient must meet the eligibility criteria for donation and kidney transplantation respectively at the Hospital Clinic of Barcelona and the national guidelines.
• Presence of donor-specific antibody/crossmatch positive (DSA/FC-XM+) non-HLA identical donor.

• at least one DSA with MFI >3.000.
• and DSA MFI <10.000 (in serum samples diluted 1/64).
• and maximum two Class II DSAs.
• and maximum 17 points in Jordan RIS Score (DSA 2500-5000: 2 points; DSA MFI 5001-10000: 5 points; DSA MFI > 10000: 10 points)
• Women of childbearing age must take contraceptive measures because Imlifidase is not recommended during pregnancy.
• Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.

Exclusion Criteria

Participants who meet any of the following criteria will be excluded from participation in this study:

1. Known contraindications for therapy with IVIG, Rituximab, plasma exchange (PLEX) or Imlifidase.

2. Recipients of Deceased Donors (DBD, Extended Criteria Donors (ECD) or DCD).

3. A positive Complement-Dependent Cytotoxicity (CDC) Crossmatch against the living donor.

4. HIV-positive subjects.

5. Subjects who test positive for HBV infection [positive HBVsAg or HBVeAg/DNA] or HCV infection [RNA+].

6. Subjects with active TB.

7. Subjects with selective IgA deficiency, those who have known anti-IgA antibodies, and those with a history of anaphylaxis or severe systemic responses to any part of the clinical trial material.

8. Subjects who have received or for whom multiple organ transplants are planned.

9. A significantly abnormal general serum screening lab result defined as WBC<3.0x103/ml, Hgb<8.0 g/dL, platelet count <100x103/ml, SGOT>3xupper limit.

10. Subjects with active CMV or EBV infection as defined by positive PCR.

11. Subjects with a known history of previous myocardial infarction within one year of screening.

12. Subjects with a history of clinically significant thrombotic episodes, and subjects with active peripheral vascular disease.

13. Patients with a kidney disease with high risk of recurrence and/or complement-associated kidney disease (aHUS, etc).

14. Subjects with Protein C and Protein S deficiency.

15. Pregnant and lactating women

16. Current diagnosis or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP.

17. Known allergy to Imlifidase or excipient of the drug preparation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundacion Clinic per a la Recerca Biomédica

OTHER

Sponsor Role: lead

Responsible Party

Anna Cruceta

Clinical Research Manager

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fritz Diekmann, Dr

Role: PRINCIPAL_INVESTIGATOR

Fundació de Recerca Clínic Barcelona - Institut D'Investigacions Biomèdiques Agustí Pí i Sunyer

Other Identifiers

2024-513607-14-00

Identifier Type: CTIS

Identifier Source: secondary_id

LIVEDES study

Identifier Type: -

Identifier Source: org_study_id