Felzartamab in Recipients of Kidney Transplants With Late Isolated Microvascular Inflammation

What is the Purpose of this Study?

The goal of this study is to evaluate the safety and effectiveness of an investigational drug called felzartamab in people who have received a kidney transplant and may have late isolated microvascular inflammation (MVI). MVI is a complication after transplant surgery in which the immune system attacks the organ that was transplanted (in this case, the kidney) and causes tissue damage to the new organ. Felzartamab is monoclonal antibody (a type of laboratory-made substance) designed to reduce specific immune cells that drive inflammation and damage in transplanted kidneys. Study procedures include electrocardiograms, kidney biopsies, felzartamab, and/or placebo (inactive substance) infusions, and laboratory assessments. Researchers also aim to assess how felzartamab is processed though the body, as well as how the drug works on the immune system.

Eligibility

* 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

Key Inclusion Criteria:

* 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.

Key Exclusion Criteria:

* 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.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

A Double-Blind, Placebo-Controlled, Multicenter, Randomized Phase 2 Trial Evaluating the Efficacy and Safety of Felzartamab in Recipients of Kidney Transplants with Late Isolated Microvascular Inflammation -

Study Details

Disease Type/Condition

Other

Principal Investigator

Huang, Edmund

Co-Investigators

Alice Peng, Ashley Vo, Jun Shoji, Noriko Ammerman, Reiad Najjar, Sindhu Chandran, Stanley Jordan

Age Group

Adult

Phase

IRB Number

STUDY00004291

ClinicalTrials.gov ID

NCT07219043

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Email

clinicaltrials@cshs.org