Antibody-mediated rejection (AMR) is a major cause of worsening kidney function after a kidney transplant (kidney allograft dysfunction) and can lead to kidney failure. AMR happens when the kidney recipient's immune system makes antibodies that attack the donor kidney. Antibodies are proteins made by the immune system to recognize foreign cells. Over time, this attack can damage kidney tissue and cause the transplant to fail. Because AMR can be serious, there is a need for treatments that are safe, work well, and are supported by good evidence.
The main aim of this study is to find out how safe mezagitamab is and how well adults with AMR tolerate it compared with placebo. A placebo looks like medicine but has no active ingredients. The study will also look at whether mezagitamab helps to control inflammation in the transplanted kidney and helps keep kidney function stable, compared with placebo.
Participants will be placed by chance in 1 of the 3 treatment groups in equal numbers. Two groups will receive mezagitamab in two different doses. One group will receive placebo. This means that out of every 3 participants, 2 will receive mezagitamab and 1 will receive placebo.
During the study, participants will visit their study clinic several times.
The participant aged 18 to 80 years.
The participant must have a biopsy-confirmed diagnosis of active or chronic active late AMR (defined as greater than [>] 6 month after kidney transplant) without concurrent definitive TCMR (Grade 1a and above) as defined by the 2022 Banff classification.
Biopsy within 30 days prior to screening, or performed during screening period within protocol-defined window.
If the participant has received treatment for rejection, then the repeat biopsy and donor specific antibody (DSA) testing must have been performed at least 6 weeks after stopping the treatment.
The participant has blood type A, B, AB, or O (ABO) incompatible transplant.
The participant has a history of multiple organ transplants, including en bloc and dual kidney transplants.
Participant likely to require renal replacement therapy within the subsequent 30 days.
Participants who have received an anti-cluster of differentiation 38 (CD38) therapy in the last 1 year or have past history of failing to achieve AMR resolution despite treatment with an anti-CD38 therapy.
Parallel
Mezagitamab
DrugMezagitamab subcutaneous (SC) injection.
Placebo
DrugMezagitamab-matching placebo SC injection.
Arms A, B, and C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of the trial intervention, whether or not the occurrence is considered related to the trial intervention. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the trial intervention. TEAEs are defined as AEs with start dates at the time of or following the first exposure to investigational medicinal product (IMP).
Arms A, B, and C: Number of Participants With Related TEAEs
A related AE is an AE that is considered related to the IMP. Related TEAEs are defined as related AEs with start dates at the time of or following the first exposure to IMP.
Arms A, B, and C: Number of Participants With Serious Adverse Events (SAEs)
An SAE is any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect.
Arms A, B, and C: Number of Participants With AEs of Special Interest
AEs of special interest are AEs that are considered specific to the IMP.
Arms A, B, and C: Percentage of Participants With Achievement of Biopsy-Proven Histologic Resolution of AMR Activity at Weeks 24 and 48
Achievement of biopsy-proven histological resolution of AMR activity will be assessed by the 2022 Banff classification criteria. The Banff 2022 Classification provides a standardized framework for evaluating kidney transplant biopsies using lesion scoring.
Arms A, B, and C: Microvascular Inflammation (MVI) Score in Biopsy Samples at Weeks 24 and 48
MVI is an important marker of allograft loss and is defined as the sum of glomerulitis and peritubular capillaritis scores (g+ptc) on kidney histology.
Arms A, B, and C: Percentage of Participants Who Achieve a MVI Score of 0 at Weeks 24 and 48
Arms A, B, and C: Change From Baseline in MVI score at Weeks 24 and 48
This trial is not recruiting at the moment. You can still explore other options: