OM336 in Sensitized Transplant Candidates

This investigator-initiated, single-arm, open-label Phase IIa pilot study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of OM336 in highly HLA-sensitized adults with chronic kidney disease awaiting kidney transplantation. The study will enroll 12 participants who have either a very low likelihood of receiving a compatible deceased donor kidney because of broad HLA sensitization or unacceptable donor-specific antibodies against a potential living donor. Participants will receive one 4-week course of subcutaneous OM336, with the option of a second 4-week course based on the change in virtual panel-reactive antibody (vPRA) levels after the initial treatment period. Participants will subsequently be followed for up to 24 months and, if transplantation occurs, for at least 12 months after transplantation. The primary objectives are to evaluate the safety and tolerability of OM336 through Week 24 and (co-primary endpoint) its effect on HLA sensitization, assessed by changes in vPRA levels at Week 24. Secondary and exploratory objectives include assessment of the durability of changes in vPRA and donor-specific antibodies, the number of potential compatible donors, transplantation rates, OM336 pharmacokinetics and immunogenicity, and effects on B-cell and plasma-cell immunity and antibody characteristics. An optional substudy will assess B-cell immunity in bone marrow and lymph-node samples.

Inclusion Criteria: * Biologic male or female, 18 to 70 years of age at the time of informed consent. * Capable of and willing to provide signed informed consent (ICF); subject must sign ICF indicating that he or she understands the purpose of procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the subject's disease. * Willing and able to comply with the visits, treatments, procedures, laboratory tests, and other requirements according to the current protocol, with a high probability for adherence and completion of the study. * Presensitized patient 1. Deceased kidney donor transplant candidate Broadly sensitized recipient on deceased donor waiting list: inclusion in the AM program (\>85% vPRA) for ≥24 months or inclusion in the ETKAS scheme and \>95% vPRA for ≥24 months, but not fulfilling the criteria in the AM program (panel reactivity includes specificities that are not acceptable by the local center; e.g. HLA antibodies with an MFI \>10.000 but no prior sensitizing event documented). AND: A dilution of the baseline serum obtained at screening by 1:100 must lead to a considerable decrease in HLA antibody MFI, with a decrease in vPRA levels by at least 1.0%. OR 2. Living donor kidney transplant candidate Living donor transplant candidate with, according to local policy, unacceptable DSA against the scheduled donor and no option of kidney paired donation (KPD) transplantation, or within a KPD program with no transplant offer after 12 months of listing. AND: A dilution of the baseline serum obtained at screening by 1:100 must lead to a negative DSA result or to a considerable decrease in DSA MFI to permissive levels per local lab. * Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening using a highly sensitive pregnancy test. Women of childbearing potential and fertile men who are sexually active must agree to use a highly effective method of contraception (\2 × the upper limit of normal (ULN) except if due to Gilbert syndrome; Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) \>3 × ULN * Currently enrolled in or participated in another clinical research study with investigational drug or device within 30 days or 5 drug half-lives of the investigational product (whichever is longer), prior to screening. * Any clinically significant underlying illness that, in the opinion of the Investigator, may compromise study participation, present a safety risk to the participant, or may confound the interpretation of the study results, including general non-adherence to medication * Known allergy to dexametasone and its excipients, diphenhydramine and its excipients, acetaminophen and its excipients or to valacyclovir and its excipients.