A Study to Learn About the Effects of Felzartamab Infusions in Adults With Kidney Transplants Who Have Late Isolated Microvascular Inflammation

The primary objective of the study is to evaluate the efficacy of felzartamab compared to placebo in kidney transplant recipients in Cohort 1 (Part A). The secondary objectives of the study are to evaluate the efficacy of felzartamab compared to placebo through additional clinical endpoints (Part A), summarize efficacy of felzartamab up to Week 52 in kidney transplant recipients in Cohorts 1 and 2 (Part B); evaluate safety of felzartamab in kidney transplant recipients in Cohorts 1 and 2 (Parts A and B) and to assess the pharmacokinetic (PK) profile and immunogenicity of felzartamab (Parts A and B).

Age

18–74

Sex

ALL

Healthy volunteers

Not accepted

You may be eligible if

MVI (MVI ≥2), donor specific antibody (DSA)-negative that is either complement activation (C4d) negative or C4d positive (biopsy-confirmed) without T cell-mediated rejection (TCMR) per central reading, as defined by the Banff 2022 criteria.
Biopsy must be within 3 months (preferably within 1 month) prior to randomization and meet adequate criteria (option a preferred over option b):
1. Adequate: 10 or more non-sclerotic/evaluable glomeruli and two muscular arteries
2. Minimally Adequate: at least 7 non-sclerotic/evaluable glomeruli and one muscular artery
For participants who received any prior treatment for antibody-mediated rejection (AMR), MVI, or TCMR as outlined in Exclusion Criterion 5, the biopsy must be performed at least 6 weeks after completing (or stopping) prior treatment.
Kidney transplant at least 6 months prior to Screening visit (recipients of either living or deceased donors).
DSA: Human leukocyte antigen (HLA) Class I and II antigen-specific DSA-negative (preformed and de novo DSA) as determined by the local laboratory's definition of positivity using single-antigen bead-based assays within 3 months prior to randomization.

You may not be if

Transplant: Blood type (ABO)-incompatible transplant.
History of multiple organ transplants including en bloc and dual kidney transplants.
Presence of HLA donor-specific antibodies.
Acute, rapid decline in renal function, defined as a participant likely to require renal replacement therapy within the next 30 days as determined by the Investigator.
Prior AMR or TCMR treatment (with the exception of corticosteroids) within 3 months prior to randomization is excluded as listed below. Participants who received any of these treatments between 3 and 6 months prior to randomization must have both a renal biopsy (IC3) and DSA testing at least 6 weeks after completing (or stopping) treatment in order to confirm continuing MVI≥2 and DSA negative status and to determine eligibility:
1. Intravenous or subcutaneous immunoglobulin (IVIg or subcutaneous immunoglobulin \[SCIg\]) or plasma exchange (PLEX).
2. Complement system inhibitors (e.g., eculizumab).
3. Proteasome inhibitors (e.g., bortezomib).
4. The anti-interleukin-6 receptor (anti-IL-6R) tocilizumab.
5. Any B cell-depleting therapy (including anti-CD20 agents \[e.g., rituximab\]) within 3 months prior to randomization.
6. Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization.

What this study is about