Clinical trial NCT06461546: Imlifidase in Living Donor Renal Transplantation Highly Sensitized Recipients
Official title: Imlifidase in Living Donor Renal Transplantation Highly Sensitized Recipients (LIVEDES)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Kidney Transplant Candidates
Keywords: living kidney trasplant
imlifidase treatment
Lead sponsor: Fundacion Clinic per a la Recerca Biomédica
Sponsor class: OTHER
First posted: 2024-06-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:Inclusion Criteria To be eligible to participate in this study, candidates must meet the following elegibility criteria. Currently, at the Hospital Clinic of Barcelona, up to 10 highly sensitized patients would meet the following inclusion criteria.

* Participant 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:

• Participant Exclusion Criteria

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

Primary outcomes:
measure: • Proportion of patients with conversion of a positive virtual crossmatch to negative within 6 hours after imlifidase treatment (up to two doses).
timeFrame: 6 hours
Secondary outcomes:
measure: 1. Proportion of patients that require a second dose of imlifidase
timeFrame: 24 hours
measure: 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)
timeFrame: daily, from day 0 to day 14
measure: 3. De novo DSA appearance over 14 days after imlifidase treatment
timeFrame: daily, from day 0 to day 14
measure: 4. To evaluate HLA/DSA antibody levels up to 1 year after transplantation
timeFrame: time points between pre-dose imlifidase and 2 weeks, and at 1, 3 and 6 months and 1 year after imlifidase treatment
measure: 5. To evaluate renal function up to 1 year after transplantation
timeFrame: time points between 24 hours and 2 weeks and at 1, 3 and 6 months and 1 year after transplantation as assessed
measure: 6. To evaluate patient survival 1 year after transplantation
timeFrame: at 12 months after transplantation
measure: 7. To evaluate the graft survival at 12 months
timeFrame: at 12 months after transplantation
measure: 8. Proportion of patients with biopsy confirmed rejection, either cell-mediated or antibody-mediated rejection, over 1 year
timeFrame: within 12 months
measure: 9. To evaluate safety of Imlifidase treatment with regards to infusion related reactions occurring within 48 hours of Imlifidase infusion
timeFrame: within 48 hours of Imlifidase infusion
measure: 10.adverse events within 30 days after transplantation
timeFrame: 30 days after transplantation
measure: 11. Proportion of patients with severe or serious infections
timeFrame: 6 months and 12 months
measure: 12. To evaluate safety of Imlifidase treatment with regards to reported serious adverse events (SAEs)
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Fundació de Recerca Clínic Barcelona - Institut D'Investigacions Biomèdiques Agustí Pí i Sunyer
name: Fritz Diekmann, Dr
role: PRINCIPAL_INVESTIGATOR
References: