A Study to Evaluate How Pozelimab + Cemdisiran Combination Therapy Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Whose Current Treatment is Not Working Efficiently

Официальное название

A Single Arm Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Control of Intravascular Hemolysis on Currently Available C5 Inhibitor Therapy

Обзор

This study is researching a treatment combination with two experimental drugs called pozelimab and cemdisiran referred to as "study drugs". Researchers are looking for a better way to treat Paroxysmal Nocturnal Hemoglobinuria (PNH). The aim of the study is to see how well the pozelimab and cemdisiran combination works to lower hemolysis in participants whose PNH has been not well controlled even after taking other complement component 5 (C5) inhibitors, eculizumab/eculizumab biosimilar, ravulizumab or crovalimab. The study is looking at several other research questions, including: * What side effects may happen from taking the study drugs? * How much of the study drugs are in the blood at different times? * Whether the body makes antibodies against the study drug (which could make the study drugs not work as well or could lead to side effects)

Подробное описание

The treatment period has two parts, a Treatment Period (TP, 28 weeks) and an Extension treatment Period (EP, 52 weeks).

Вмешательства

• Препарат Pozelimab
  Administered per the protocol
• Препарат Cemdisiran
  Administered per the protocol

Первичные конечные точки

• Percent change in Lactate Dehydrogenase (LDH) during TP [Срок оценки: From baseline to week 28]

Вторичные конечные точки (12)

• Normalization of LDH [Срок оценки: Through week 52]
• Adequate control of hemolysis (LDH ≤1.5 × ULN) [Срок оценки: Through week 52]
• Transfusion avoidance [Срок оценки: Through week 52]
• Hemoglobin stabilization [Срок оценки: Through week 52]
• Change in hemoglobin from baseline [Срок оценки: Through week 52]
• Change in fatigue [Срок оценки: Through week 52]
• Occurrence of all Adverse Events (AEs) [Срок оценки: Through week 52]
• Severity of all AEs [Срок оценки: Through week 52]
• Occurrence of all Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: Through week 52]
• Severity of all TEAEs [Срок оценки: Through week 52]
• Change from baseline in Total Complement Hemolytic Activity Assay (CH50) [Срок оценки: Through week 52]
• Concentrations of total pozelimab [Срок оценки: Through week 52]

Критерии участия

Критерии включения

• Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
• Currently treated with marketed eculizumab, ravulizumab, or crovalimab at the labeled dose for at least 6 months
• LDH persistently > 1.5 × Upper Limit of Normal (ULN) in the previous 6 months that the Principal Investigator (PI) attributes is due to intravascular hemolysis
• At least 2 screening LDH values from different visits as described in the protocol
• Willing and able to comply with clinic/remote visits and study-related procedures, including completion of the full series of meningococcal vaccinations required per protocol and agreement to continue to remain up to date with these vaccinations during the study

Критерии исключения

• Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplants
• Body weight <40 kilograms at screening visit
• Patients with a known or suspected C5 mutation that is refractory to their current C5i treatment as described in the protocol
• Any active or ongoing infection within 2 weeks of screening or during the screening period or any recent infection as described in the protocol
• Known hereditary complement deficiency

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 5 центров

• Seoul National University Hospital — Seoul
• Severance Hospital — Seoul
• Seoul St. Mary's Hospital - The Catholic University of Korea — Seoul
• Ewha Womans University Mokdong Hospital — Seoul
• Samsung Medical Center — Seoul

Испания · 5 центров

• Hospital Universitario Basurto — Bilbao
• Institut Catala d'Oncologia — Barcelona
• Hospital San Pedro de Alcantara — Cáceres
• Hospital General JM Morales Meseguer — Murcia
• Hospital Universitario de Salamanca — Salamanca

Бразилия · 3 центра

• Hospital das Clinicas da FMRP USP — Ribeirão Preto
• Faculdade de Medicina do ABC — Santo André
• Hospital Santa Marcelina — São Paulo

Италия · 3 центра

• Universita Cattolica del Sacro Cuore - Policlinico Universitario A. Gemelli — Rome
• AOU Careggi — Florence
• SC Hematology, AOU Città della Salute e della Scienza di Torino — Torino

Turkey (Türkiye) · 2 центра

• Istanbul University Istanbul Faculty of Medicine — Istanbul
• Ege University — Izmir

Канада · 1 центр

• CISSS-CA — Lévis

Польша · 1 центр

• In-Vivo Sp. z o.o. — Bydgoszcz

Идентификаторы

NCT: NCT07154745 · R3918-PNH-2483 · 2024-519709-37-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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