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

Официальное название

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 (MVI)

Обзор

In this study, researchers will learn more about a drug called felzartamab in people who have received a kidney transplant and later developed a condition called microvascular inflammation (MVI). MVI is a type of injury to small blood vessels in the transplanted kidney and may be a sign of rejection by the body. It can lead to serious kidney problems over time. In many cases, MVI is caused by antibodies that attack the transplanted kidney. But in some people, MVI happens without these antibodies. This type of MVI is called isolated MVI. There are currently no approved treatments for isolated MVI. The main goal of the study is to learn about the effect felzartamab has on inflammation in the transplanted kidney. The main question researchers want to answer is: • How many participants have no signs of active inflammation in the transplanted kidney after 24 weeks of treatment with felzartamab? Researchers will also study how felzartamab affects kidney function, immune activity, and overall health. They will monitor safety through kidney biopsies, lab tests, and by recording adverse events throughout the study. Adverse events are health problems that may or may not be caused by the study drug. The study will be done in 2 parts as follows: * Participants will be randomly assigned to receive either felzartamab or a placebo. A placebo looks like the study drug but contains no real medicine. * In Part A, participants will receive their assigned drug for 24 weeks. Neither the researchers nor the participants will know who is receiving felzartamab or placebo. * Part B will last another 28 weeks. All participants will receive felzartamab and both participants and researchers will know this. * All treatments will be given by intravenous (IV) infusion at the study site. * Participants will have kidney biopsies at the start of the study, at Week 24, and at Week 52 to help measure changes in inflammation. * Participants will stay in the study for about 1 year.

Подробное описание

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).

Вмешательства

• Препарат Felzartamab
  Administered IV
• Препарат Placebo
  Administered IV

Первичные конечные точки

• Part A: Percentage of Participants Who Achieve Biopsy-proven Histologic Resolution (BPHR) [Срок оценки: Week 24]

Вторичные конечные точки (12)

• Part A: Microvascular Inflammation (MVI) Score [Срок оценки: Week 24]
• Part A: Percentage of Participants Who Achieve an MVI Score of 0 [Срок оценки: Week 24]
• Part A: Change from Baseline in Estimated Glomerular Filtration Rate (eGFR) [Срок оценки: Baseline, Week 24]
• Part A: Percentage of Participants in Cohort 2 Who Achieve BPHR [Срок оценки: Week 24]
• Part B: Percentage of Participants Who Achieve BPHR [Срок оценки: Weeks 24 and 52]
• Part B: MVI Score [Срок оценки: Weeks 24 and 52]
• Part B: Percentage of Participants Who Achieve an MVI Score of 0 [Срок оценки: Weeks 24 and 52]
• Part B: Change from Baseline in eGFR [Срок оценки: Baseline, Weeks 24 and 52]
• Part B: Time to All-cause Allograft Loss [Срок оценки: Up to Week 52]
• Parts A and B: Number of Participants with Adverse Events (AEs) [Срок оценки: From first dose of study drug up to end of study follow-up (up to week 57)]
• Parts A and B: Percentage of Participants with T Cell-mediated Rejection (TCMR) by Biopsy [Срок оценки: Weeks 24 and 52]
• Parts A and B: Number of Participants with Clinically Significant Laboratory Abnormalities [Срок оценки: From time of first dose to end of trial visit (Up to Week 52)]

Критерии участия

Критерии включения

• 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):

• Adequate: 10 or more non-sclerotic/evaluable glomeruli and two muscular arteries
• 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.

Критерии исключения

• 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:

• Intravenous or subcutaneous immunoglobulin (IVIg or subcutaneous immunoglobulin \[SCIg\]) or plasma exchange (PLEX).
• Complement system inhibitors (e.g., eculizumab).
• Proteasome inhibitors (e.g., bortezomib).
• The anti-interleukin-6 receptor (anti-IL-6R) tocilizumab.
• Any B cell-depleting therapy (including anti-CD20 agents \[e.g., rituximab\]) within 3 months prior to randomization.
• Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization.

Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 21 центр

• Loma Linda University Medical Center — Loma Linda
• Keck Hispital of University of Southern California (USC) — Los Angeles
• Cedars-Sinai Medical Center — Los Angeles
• Providence St. Joseph Hospital Orange — Orange
• Sutter Health - California Pacific Medical Center — San Francisco
• University of California San Fransisco (UCSF) Medical Center — San Francisco
• The University of Kansas Medical Center — Kansas City
• University of Michigan Medical Center — Ann Arbor
• … и ещё 13 центров

Франция · 4 центра

• Centre Hospitalier Universitaire (CHU) de Bordeaux - Hôpital Pellegrin — Bordeaux
• Centre Hospitalier Universitaire (CHU) de GreNble Alpes - Hôpital Michallon — La Tronche
• Hospices Civils de Lyon - Hôpital Édouard Herriot — Lyon
• Centre Hospitalier Universitaire (CHU) de Toulouse - Hôpital de Rangueil — Toulouse

Испания · 4 центра

• Hospital Del Mar — Barcelona
• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital Clínic de Barcelona — Barcelona
• Hospital Universitario Miguel Servet — Zaragoza

Германия · 3 центра

• Charité - Universitätsmedizin Berlin — Berlin
• Universitaetsklinikum Carl Gustav Carus Dresden — Dresden
• Universitätsklinikum Hamburg-Eppendorf — Hamburg

Аргентина · 2 центра

• Instituto de Trasplante y Alta Complejidad (ITAC) — Buenos Aires
• Clínica Privada Vélez Sarsfield — Córdoba

Австралия · 2 центра

• Westmead Hospital — Westmead
• Princess Alexandra Hospital — Brisbane

Бразилия · 2 центра

• Hospital de Base da Faculdade de Medicina de São José do Rio Preto — Vila São José
• Hospital do Rim - Fundação Oswaldo Ramos — São Paulo

Австрия · 1 центр

• Medizinische Universität Wien — Vienna

Канада · 1 центр

• Alberta Health Services (AHS) - University of Alberta Hospital — Edmonton

Чехия · 1 центр

• Institut klinicke a experimentalni mediciny (IKEM) — Prague

Швейцария · 1 центр

• Universitätsspital Zürich — Zurich

Идентификаторы

NCT: NCT07219043 · 299AR201 · 2025-521742-15

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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