Imlifidase in Living Donor Renal Transplantation: Highly Sensitized Recipients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Reproductive and Urinary Physiological Phenomena [G08]

Trial duration

completed 3 Dec 2024

Decision date (initial)

2024-10-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Hansa Biopharma AB

External identifiers

EU CT number

2024-513607-14-00

ClinicalTrials.gov

NCT06461546

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the ability of Imlifidase treatment to achieve a negative virtual crossmatch in patients with available live donor kidney

Secondary objectives 12

1. Proportion of patients that required a second dose of imlifidase.
2. Pre-existing DSA appearance measured daily until D+14
3. De novo DSA appearance over 14 days after imlifidase treatment
4. HLA/DSA antibody levels at several time points between pre-dose imlifidase and 2 weeks, and at 1, 3 and 6 months and 1 year after imlifidase treatment
5. Renal function at several time points between 24 hours and 2 weeks and at 1, 3 and 6 months and 1 year after transplantation as assessed by estimated glomerular filtration rate (eGFR) and serum/plasma creatinine levels
6. Patient survival at 12 months after transplantation
7. Graft survival at 12 months after transplantation
8. Proportion of patients with biopsy confirmed rejection, either cell-mediated or antibody-mediated rejection, over 1 year.
9. Proportion of patients with infusion-related reactions within 48 hours of imlifidase infusion
10. Proportion of patients with adverse events within 30 days after transplantation
11. Proportion of patients with severe or serious infections at 6 months and 12 months.
12. Safety over 1 year as measured by reported SAEs

Conditions and MedDRA coding

kidney trasplant

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. •Highly sensitized (cPRA ≥ 50%) kidney transplant candidates between 18 and 65 years.
2. • Low probability to get a transplant in a kidney exchange program (KEP) from a living donor.
3. • Included in the living donor program, with an accepted potential living donor.
4. • Donor and recipient must meet the eligibility criteria for donation and kidney transplantation respectively at the Hospital Clinic of Barcelona and the national guidelines.
5. • Presence of donor-specific antibody/crossmatch positive (DSA/FC-XM+) non-HLA identical donor. o at least one DSA with MFI >3.000. o and DSA MFI <10.000 (in serum samples diluted 1/64). o and maximum two Class II DSAs. o and maximum 17 points in Jordan RIS Score (DSA 2500-5000: 2 points; DSA MFI 5001-10000: 5 points; DSA MFI > 10000: 10 points)
6. • Women of childbearing age must take contraceptive measures because imlifidase is not recommended during pregnancy.
7. • 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 17

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 12

1. To evaluate flow cytometry T-cell crossmatch conversion within 24 hours of imlifidase treatment, requirement of a second dose of imlifidase.
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)
3. To evaluate the appearance of de novo DSAs (any DSA no present in pre-transplant or historical) daily - until D+14. To be considered positive the bead MFI should be over 750 and to be above the bead specific threshold related to the lowest bead of the same locus.
4. HLA/DSA antibody levels at several time points between pre-dose imlifidase and 2 weeks, and at 1, 3 and 6 months and 1 year after imlifidase treatment
5. Renal function at several time points between 24 hours and 2 weeks and at 1, 3 and 6 months and 1 year after transplantation as assessed by estimated glomerular filtration rate (eGFR) and serum/plasma creatinine levels
6. To evaluate patient survival 1 year after transplantation
7. To evaluate the graft survival at 12 months (both overall and death-censored analysis)
8. To evaluate the incidence of acute allograft rejection within 12 months (overall and stratified by type: cell mediated rejection or antibody-mediated rejection)
9. To evaluate safety of Imlifidase treatment with regards to infusion related reactions occurring within 48 hours of Imlifidase infusion
10. To evaluate the adverse events within 30 days after transplantation
11. To evaluate to severe or serious infections (that required hospitalization) within 30 days after transplantion, at 6 and 12 months
12. To evaluate safety of Imlifidase treatment with regards to reported serious adverse events (SAEs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Sponsor organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Address

Calle Rosellon 149-153

City

Barcelona

Postcode

08036

Country

Spain

Scientific contact point

Organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Contact name

Fritz Diekmann

Public contact point

Organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Contact name

Fritz Diekmann

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications