A Study to Assess the Effect of Surovatamig in Adult Participants With Antibody-mediated Kidney Disease

Официальное название

A Phase 2, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Surovatamig in Adults With Antibody-mediated Kidney Disease

Обзор

The purpose of this study is to assess the safety, tolerability, pharmacokinetic, and efficacy of surovatamig administered by subcutaneous injection in adult participants with primary membranous nephropathy.

Подробное описание

This is a Phase II open-label study to assess the safety, tolerability, Pharmacokinetics, and efficacy of surovatamig in adult participants with pMN, who are positive for anti-PLA2R antibodies and have heavy and persistent proteinuria with a high risk of progressing to end stage kidney disease.

The study will be conducted across approximately 30 to 40 study sites in approximately 10 countries. The study consists of 2 parts (Part A Multiple ascending with sentinel dosing and Part B Multiple ascending doses), with each consisting of 3 periods (ie, screening period, treatment period, and follow-up period; up to 26 months in total).

Вмешательства

• Препарат Surovatamig
  Participants will receive Surovatamig subcutaneously

Первичные конечные точки

• Number of participants with adverse events. [Срок оценки: Through study completion, an average of 2 years]
• Change from baseline in UPCR (from 24-hour urine collection or the intended 24-hour urine collection) [Срок оценки: At 6 months]

Вторичные конечные точки (12)

• Percentage of participants achieving complete or partial remission of pMN [Срок оценки: At 24 months]
• Percentage of participants achieving complete remission of pMN [Срок оценки: At 24 months]
• Percentage of participants achieving partial remission of pMN [Срок оценки: At 24 months]
• Change from baseline in UPCR (from 24-hour urine collection or the intended 24-hour urine collection) [Срок оценки: At 24 months]
• Change from baseline in anti-PLA2R antibody titer [Срок оценки: At 24 months]
• Change from baseline in B-cell count in peripheral blood [Срок оценки: At 24 months]
• Time to relapse after complete or partial remission [Срок оценки: At 24 months]
• Time to a ≥ 3 months sustained reduction of eGFR [Срок оценки: From Baseline to 24 months]
• Change from baseline in patient-reported experience of symptoms associated with pMN [Срок оценки: Through study completion, an average of 2 years]
• Serum PK parameters of surovatamig, AUC Area under the plasma concentration versus time curve [Срок оценки: Through study completion, an average of 2 years]
• Treatment-emergent ADAs [Срок оценки: Through study completion, an average of 2 years]
• Serum PK parameters of surovatamig, as Cmax (Peak Plasma Concentration) [Срок оценки: Through study completion, an average of 2 years]

Критерии участия

Критерии включения

• Participant must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 75 years of age inclusive, at the time of signing the informed consent.
• Diagnosis of anti-PLA2R antibody-positive pMN.
• All participants must have received SoC therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for ≥ 4 weeks, with exceptions in case of intolerance, contraindications, or low blood pressure, before the screening period.
• Positive for anti-PLA2R.
• Up to date with required vaccinations as per institutional guidelines (eg, influenza, pneumococcal, and severe acute respiratory syndrome coronavirus 2) prior to study entry.
• Male and/or female assigned at birth, inclusive of all gender identities. Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent

Критерии исключения

• Receipt of B cell-depleting therapy including CD19- or CD20-directed monoclonal antibodies < 9 months before screening.
• Immunomodulatory therapy <3 months before screening.
• Secondary causes of membranous nephropathy
• Diabetes mellitus with haemoglobin A1C > 8.5% tested at screening visit.
• Malignancies
• History of HLH/MAS. 7 Significant CNS co-morbidity

8\. History of chronic significant respiratory disease. 9. Significant opportunistic infection in the medical history deemed relevant by the Investigator.

10\. Abnormal vital sign after 10 minutes sitting at rest. 11. Administration of corticosteroids such as prednisolone at doses exceeding 20 mg or an equivalent agent < 2 months before screening.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 6 центров

• Research Site — Los Angeles
• Research Site — Iowa City
• Research Site — Bethesda
• Research Site — New York
• Research Site — Houston
• Research Site — Houston

Франция · 5 центров

• Research Site — Bordeaux
• Research Site — Créteil
• Research Site — Lyon
• Research Site — Nantes
• Research Site — Nîmes

Италия · 4 центра

• Research Site — Brescia
• Research Site — Rozzano
• Research Site — Torino
• Research Site — Verona

Испания · 2 центра

• Research Site — Barcelona
• Research Site — Madrid

Великобритания · 2 центра

• Research Site — London
• Research Site — Manchester

Бельгия · 1 центр

• Research Site — Ieper

Германия · 1 центр

• Research Site — Düsseldorf

Польша · 1 центр

• Research Site — Lodz

Идентификаторы

NCT: NCT07571746 · D740FC00001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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