A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant

Official title

A Double-Blind, Placebo-Controlled, Multicenter, Randomized, Phase 2 Trial to Evaluate the Safety and Efficacy of Mezagitamab (TAK-079) in Kidney Transplant Recipients With Late Antibody-Mediated Rejection (AMR)

Overview

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.

Interventions

• Drug Mezagitamab
  Mezagitamab subcutaneous (SC) injection.
• Drug Placebo
  Mezagitamab-matching placebo SC injection.

Primary outcome measures

• Arms A, B, and C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Time frame: Up to Week 70]
• Arms A, B, and C: Number of Participants With Related TEAEs [Time frame: Up to Week 70]
• Arms A, B, and C: Number of Participants With Serious Adverse Events (SAEs) [Time frame: Up to Week 70]
• Arms A, B, and C: Number of Participants With AEs of Special Interest [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]

Secondary outcome measures (12)

• Arms A, B, and C: Percentage of Participants With Achievement of Biopsy-Proven Histologic Resolution of AMR Activity at Weeks 24 and 48 [Time frame: Weeks 24 and 48]
• Arms A, B, and C: Microvascular Inflammation (MVI) Score in Biopsy Samples at Weeks 24 and 48 [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 [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 [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 [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]

Eligibility criteria

Inclusion criteria

• 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 with either human leukocyte antigen (HLA) class I and/or II DSA.
• eGFR > 30 milliliters per minute per 1.73 square meters (mL/min/1.73m\^2).

Exclusion criteria

• 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.
• The participant has received any previous treatment with other immunosuppressant or immunomodulatory therapy:

a) Within 6 months of signing the informed consent form (ICF) as listed below:

• Complement system inhibitors (such as, eculizumab).
• Proteasome inhibitors (such as, bortezomib).
• Interleukin-6 (IL-6)/IL-6R antibody (such as, tocilizumab).
• Anti-cluster of differentiation 20 (CD20) antibody (such as, rituximab). b) Within 6 weeks of signing the ICF as listed below:
• Intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) or plasmapheresis
• The participant has active infection with hepatitis B virus, hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
• Participant with serious infection within 2 weeks or with opportunistic infection within 2 months prior to signing ICF. Participant with active or untreated tuberculosis, or those with high suspicion of tuberculosis are also excluded.
• History of malignancy (including myelodysplastic syndrome) within 5 years of signing the ICF, except for adequately treated non-melanoma skin cancer, superficial bladder cancer, and curatively treated cervical carcinoma-in-situ.

Key Note: Other protocol specified inclusion and exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07613359 · TAK-079-2002 · 2026-526239-20-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗