An Open Label, Phase II Study to Investigate DSA Rebound in Patients With a Positive Crossmatch, Made Transplantable With Imlifidase

18-HMedIdeS-16

The purpose of this study is to assess whether imlifidase in combination with bortezomib, belatacept, rituximab and IVIg can suppress donor specific antibodies (DSA) and the occurrence of antibody-mediated rejection (AMR) in highly sensitized patients with chronic kidney disease with a positive crossmatch towards their living donor during a period of 3 months from transplantation.

2022-12-16

2024-03-01

2024-06-01

Active (not recruiting)

Early phase I

3

Inclusion Criteria: * Signed Informed Consent obtained before any trial-related procedures * Male or female age 18 to 70 years at the time of screening * Highly sensitized patients registered on the UNOS waiting list for kidney transplantation, with either of the following: * cPRA ≥ 99.9% * cPRA ≥ 98% and have been in kidney paired donation or kidney paired exchange programs for at least 1 year * A positive crossmatch towards a living donor * Willingness and ability to comply with the protocol Exclusion Criteria: * Previous treatment with imlifidase * Previous high dose IVIg treatment (2 g/kg) within 28 days prior to imlifidase treatment * Breast-feeding or pregnancy * Women of child-bearing potential not willing or able to practice FDA-approved forms of contraception. Two medically acceptable methods of highly effective contraception must be used for the duration of the study (e.g. oral, transdermal, intravaginal, injectable or implantable contraceptive; intrauterine device; intrauterine hormone-releasing system; vasectomized partner; bilateral tubal occlusion; or double-barrier method). For a woman to be considered postmenopausal this ascertainment must be made according to medical records and clinical history and may be aided by measurement of elevated postmenopausal serum gonadotropin levels (FSH). * ABO blood group incompatible transplantations (A2 and A2B kidneys will not be accepted for B recipients) * Positive serology for HIV * Clinical signs of HBV, HCV, CMV, or EBV infection * EBV seronegative or with unknown EBV serostatus * Positive SARS-CoV-2 tests at any time point from screening to transplantation * Active tuberculosis * Ongoing serious infections as judged by the investigator * Severe other conditions requiring treatment and close monitoring e.g. cardiac failure ≥ grade 4 (New York Heart Association), unstable coronary disease or oxygen dependent respiratory disease * A history of a proven hypercoagulable condition * Present, or history of, thrombotic thrombocytopenic purpura (TTP) or known familial history of TTP * Intake of investigational drugs (other than imlifidase) within 5 half-lives * Contemporaneous participation in a medical device study * Known allergy/sensitivity (except local reactions) to imlifidase or to any drug (or the excipients) specified in the protocol * Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the trial activities * Inability by the judgement of the investigator to participate in the trial for any other reason

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 3, 'type': 'ACTUAL'}}

2023-12-01