Imlifidase in Living Donor Renal Transplantation Highly Sensitized Recipients

NCT06461546 | Withdrawn Phase 2 DMC

• 2 other identifiers: LIVEDES study2024-513607-14-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Kidney Transplant Candidates

Keywords

living kidney trasplant; imlifidase treatment

Outcome Measures

Primary Outcomes (1)

• • Proportion of patients with conversion of a positive virtual crossmatch to negative within 6 hours after imlifidase treatment (up to two doses).

  The fraction of patients with a conversion of a positive FC-XM within 6 hours of treatment with imlifidase.

  6 hours

Secondary Outcomes (12)

• 1. Proportion of patients that require a second dose of imlifidase

  24 hours

• 2. To evaluate the rebound of preexisting donor specific antibodies (DSA) (difference between MFI of each DSA daily - until D+14 - compared to pre-imlifidase administration)

  daily, from day 0 to day 14

• 3. De novo DSA appearance over 14 days after imlifidase treatment

  daily, from day 0 to day 14

• 4. To evaluate HLA/DSA antibody levels up to 1 year after transplantation

  time points between pre-dose imlifidase and 2 weeks, and at 1, 3 and 6 months and 1 year after imlifidase treatment

• 5. To evaluate renal function up to 1 year after transplantation

  time points between 24 hours and 2 weeks and at 1, 3 and 6 months and 1 year after transplantation as assessed

Study Arms (1)

Imlifidase treatment

EXPERIMENTAL

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.

Drug: Imlifidase

Interventions

Imlifidase 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.

Imlifidase treatment

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Participants who meet any of the following criteria will be excluded from participation in this study:
• Known contraindications for therapy with IVIG, Rituximab, plasma exchange (PLEX) or Imlifidase.
• Recipients of Deceased Donors (DBD, Extended Criteria Donors (ECD) or DCD).
• A positive Complement-Dependent Cytotoxicity (CDC) Crossmatch against the living donor.
• HIV-positive subjects.
• Subjects who test positive for HBV infection \[positive HBVsAg or HBVeAg/DNA\] or HCV infection \[RNA+\].
• Subjects with active TB.
• 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.
• Subjects who have received or for whom multiple organ transplants are planned.
• 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.
• Subjects with active CMV or EBV infection as defined by positive PCR.
• Subjects with a known history of previous myocardial infarction within one year of screening.
• Subjects with a history of clinically significant thrombotic episodes, and subjects with active peripheral vascular disease.
• Patients with a kidney disease with high risk of recurrence and/or complement-associated kidney disease (aHUS, etc).
• Subjects with Protein C and Protein S deficiency.

Sponsors & Collaborators

• Fundacion Clinic per a la Recerca Biomédica: lead

MeSH Terms

Interventions

Mac-1-like protein, Streptococcus

Study Officials

• Fritz Diekmann, Dr

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Research Manager

Model Details: Phase II, prospective, single arm pilot study. To evaluate the ability of Imlifidase treatment to achieve a negative virtual crossmatch in patients with available live donor kidney.

Study Record Dates

• First Submitted: June 11, 2024
• First Posted: June 17, 2024
• Study Start: October 22, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: March 12, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share