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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
36
Mezagitamab subcutaneous (SC) injection.
Mezagitamab-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).
Time frame: Up to Week 70
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.
Time frame: Up to Week 70
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.
Time frame: Up to Week 70
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.
Time frame: Up to Week 70
Arms A, B, and C: Number of Participants With AE Leading to Treatment Discontinuation
Time frame: Up to Week 70
Arms A, B, and C: Number of Participants With Clinically Significant Abnormal Laboratory Test Results and Vital Signs
Time frame: Up to Week 70
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.
Time frame: Weeks 24 and 48
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.
Time frame: Weeks 24 and 48
Arms A, B, and C: Percentage of Participants Who Achieve a MVI Score of 0 at Weeks 24 and 48
Time frame: Weeks 24 and 48
Arms A, B, and C: Change From Baseline in MVI score at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
Arms A, B, and C: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Weeks 24, 48 and 70
eGFR is a measure of kidney function calculated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
Time frame: Baseline, Weeks 24, 48 and 70
Arms A, B, and C: Change From Baseline in Donor-Derived Cell-Free DNA (dd-cfDNA) at Weeks 24, 48 and 70
dd-cfDNA are DNA fragments released from injured donor cells. It serves as a noninvasive, quantitative method that reflects allograft injury and is associated with AMR activity in kidney transplant recipients.
Time frame: Baseline, Weeks 24, 48 and 70
Arms A, B, and C: Change From Baseline in Urine Protein Creatinine Ratio (UPCR) at Weeks 24, 48 and 70
UPCR is a measure of protein excretion calculated from a urine sample, as the ratio of urine protein to creatinine, and used to assess kidney function.
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Time frame: Baseline, Weeks 24, 48 and 70
Arm B: Percentage of Participants With Achievement of Biopsy-Proven Histologic Resolution of AMR Activity at Week 70
Time frame: Week 70
Arm B: MVI Score in Biopsy Samples at Week 70
Time frame: Week 70
Arm B: Percentage of Participants Who Achieve a MVI Score of 0 at Week 70
Time frame: Week 70
Arm B: Change From Baseline in MVI score at Week 70
Time frame: Week 70
Arms A, B, and C: Percentage of Participants With T-Cell Mediated Rejection (TCMR) by Biopsy at Weeks 24 and 48
Time frame: Weeks 24 and 48
Arm B: Percentage of Participants With TCMR by Biopsy at Week 70
Time frame: Week 70
Arms A and B: Serum Concentration of Mezagitamab
Time frame: Pre-dose and at multiple time points post-dose up to Week 70
Arms A, B and C: Number of Participants With Anti-Drug Antibody
Time frame: Pre-dose and at multiple time points post-dose up to Week 70
Arms A, B and C: Number of Participants With Neutralizing Antibody
Time frame: Pre-dose and at multiple time points post-dose up to Week 70