Контролируемое равулизумабом исследование не меньшей эффективности для оценки эффективности и безопасности комбинированной терапии позелимабом и кемдисираном у взрослых пациентов с пароксизмальной ночной гемоглобинурией, которые ранее не получали ингибиторы комплемента или недавно не получали терапию ингибиторами комплемента (ACCESS-1)
Рандомизированное, открытое, контролируемое равулизумабом исследование не меньшей эффективности для оценки эффективности и безопасности комбинированной терапии позелимабом и чемдисираном у пациентов с пароксизмальной ночной гемоглобинурией, которые ранее не лечились ингибиторами комплемента или недавно не получали терапию ингибиторами комплемента
This study is researching a clinical treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH and how the combination compares with 2 existing treatments: ravulizumab and eculizumab.
The pozelimab + cemdisiran combination may be referred to as "study drugs". Ravulizumab and eculizumab may also be called the "comparator drug".
The study is looking at several research questions, including:
- How effective is the pozelimab + cemdisiran combination compared to ravulizumab?
- How effective is pozelimab + cemdisiran combination compared to eculizumab?
- What side effects may happen from taking the study drugs?
- How much study drugs are in the blood at different times?
- Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects)
Обзор исследования
Статус
Вмешательство/лечение
Тип исследования
Регистрация (Действительный)
Фаза
- Фаза 3
Контакты и местонахождение
Места учебы
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São Paulo, Бразилия, 08270-070
- Casa de Saude Santa Marcelina
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São Paulo, Бразилия, 01321-001
- A Beneficencia Portuguesa de Sao Paulo, BP Mirante
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São Paulo
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Santo André, São Paulo, Бразилия, 09060-650
- Centro de Estudos e Pesquisas em Hematologia e Oncologia
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Budapest, Венгрия, 1083
- Semmelweis University
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Thessaloniki, Греция, 57010
- George Papanikolaou Hospital
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Jaipur, Индия, 302017
- Bhagwan Mahaveer Cancer Hospital and Research Centre (BMCHRC)
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Kerala
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Kannur, Kerala, Индия, 670103
- Malabar Cancer Center, Kerala
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Kochi, Kerala, Индия, 682041
- Amrita Institute of Medical Sciences (AIMS) and Research Centre Aims
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Maharashtra
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Mumbai, Maharashtra, Индия, 400022
- K J Somaiya Super Specialty Hospital & Research Centre
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National Capital Territory of Delhi
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New Delhi, National Capital Territory of Delhi, Индия, 110085
- Rajiv Gandhi Cancer Institute & Research Center (RGCIRC) - Rohini Campus
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Punjab
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Chandigarh, Punjab, Индия, 708248
- Postgraduate Institute of Medical Education & Research (PGIMER)
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Uttar Pradesh
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Lucknow, Uttar Pradesh, Индия, 226014
- Sanjay Gandhi Postgraduate Institute of Medical Sciences
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Lucknow, Uttar Pradesh, Индия, 226003
- King George Hospital
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Amman, Иордания, 11942
- Jordan University Hospital (JUH)
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Barcelona, Испания, 08036
- Hospital Clinic de Barcelona
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Murcia, Испания, 30008
- Hospital General JM Morales Meseguer
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Salamanca, Испания, 37007
- Hospital Clinico Universitario de Salamanca
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Vizcaya
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Bilbao, Vizcaya, Испания, 48013
- Hospital Universitario Basurto
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Turin, Италия, 10126
- Hematology Citta della Salute e della Scienza di Torino
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Firenze
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Florence, Firenze, Италия, 50139
- Aou Careggi
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Roma
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Rome, Roma, Италия, 00168
- Fondazione Policlinico Universitario A. Gemelli - IRCCS
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Ontario
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Toronto, Ontario, Канада, M5G 2C4
- Toronto General Hospital
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Beijing Municipality
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Beijing, Beijing Municipality, Китай, 100032
- Peking Union Medical College Hospital
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Antioquia
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Medellín, Antioquia, Колумбия, 050034
- Hospital Pablo Tobon Uribe
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Pahang
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Kuantan, Pahang, Малайзия, 25200
- Hospital Tg Ampuan Afzan
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Sabah
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Kota Kinabalu, Sabah, Малайзия, 88586
- Hospital Queen Elizabeth
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Selangor
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Ampang, Selangor, Малайзия, 68000
- Hospital Ampang
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Nuevo León
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Monterrey, Nuevo León, Мексика, 64460
- Servicio de Hematologia del Hospital Universitario de la Uanl
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Lima, Перу, 15072
- Clinica San Felipe
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Bydgoszcz, Польша, 85-168
- Szpital Uniwersytecki Nr2 Bydgoszcz
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Warsaw, Польша, 02-776
- Institute of Hematology and Transfusion Medicine
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Pomeranian Voivodeship
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Gdansk, Pomeranian Voivodeship, Польша, 80-214
- University Clinical Center Medical University of Gdansk
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Cluj
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Cluj-Napoca, Cluj, Румыния, 400015
- Ion Chiricuta Oncology Institute
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Dolj
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Craiova, Dolj, Румыния, 200143
- Municipal Hospital Filantropia
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Mureș County
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Târgu Mureş, Mureș County, Румыния, 540136
- Targu Mures Clinical County Emergency Hospital
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Singapore, Сингапур, 119074
- National University Hospital
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Leeds, Соединенное Королевство, LS9 7TF
- St James Hospital
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California
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Whittier, California, Соединенные Штаты, 90602
- The Oncology Institute of Hope & Innovation
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Bangkok, Таиланд, 10330
- King Chulalongkorn Memorial Hospital
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Chiang Mai, Таиланд, 50200
- Chaing Mai University
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Khon Kaen, Таиланд, 40002
- Faculty of Medicine Khon Kaen University
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Changwat Songkhla
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Hat Yai, Changwat Songkhla, Таиланд, 90110
- Clinical Research Center, Faculty of Medicine, Prince of Songkla University
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Changhua, Тайвань, 500-06
- Changhua Christian Hospital
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Hualien City, Тайвань, 97002
- Hualien Tzu Chi Hospital
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Kaohsiung City, Тайвань, 80756
- Kaohsiung Medical University Hospital
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Taichung, Тайвань, 4070
- Taichung Veterans General Hospital (VGHTC)
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Tainan, Тайвань, 704
- National Cheng Kung University Hospital
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Taipei, Тайвань, 114
- Tri-Service General Hospital
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Taipei, Тайвань, 100229
- National Taiwan University Hospital
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Central Taiwan
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Taichung, Central Taiwan, Тайвань, 40447
- China Medical University Hospital
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Hunan Province
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Taoyuan, Hunan Province, Тайвань, 33305
- Chang Gung Memorial Hospital - Linkou Branch
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Istanbul, Турция (Туркие), 34418
- Istanbul University
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Izmir, Турция (Туркие), 35100
- Ege University
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Central Luzon
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Quezon, Central Luzon, Филиппины, 1011
- St Lukes Medical Center
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Busan, Южная Корея, 49241
- Pusan National University Hospital
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Seoul, Южная Корея, 06351
- Samsung Medical Center
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Seoul, Южная Корея, 03722
- Severance Hospital
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Seoul, Южная Корея, 07985
- Ewha Womans University Mokdong Hospital
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Seoul, Южная Корея, 02841
- Korea University Hospital
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Seoul, Южная Корея, 065791
- Seoul St. Mary's Hospital - The Catholic University of Korea
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Gyeonggi-do
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Suwon, Gyeonggi-do, Южная Корея, 16247
- St. Vincent Hospital
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Suwon, Gyeonggi-do, Южная Корея, 16499
- Ajou University Medical Center
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Namdong-Gu
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Incheon, Namdong-Gu, Южная Корея, 21565
- Gachon University Gil Medical Center
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Aichi-ken
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Nagoya, Aichi-ken, Япония, 466-8650
- Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
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Gifu
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Ōgaki, Gifu, Япония, 503-8502
- Ogaki Municipal Hospital
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Ibaraki
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Tsukuba, Ibaraki, Япония, 305-8576
- University of Tsukuba Hospital
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Osaka
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Moriguchi, Osaka, Япония, 570-8540
- Matsushita Memorial Hospital
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Tokyo
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Shinagawa-ku, Tokyo, Япония, 141-8625
- NTT Medical Center Tokyo
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Key Inclusion Criteria:
- Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes as described in the protocol
- Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms as described in the protocol
- LDH level ≥2 × ULN at the screening visit
- 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
Key Exclusion Criteria:
- Prior treatment with eculizumab within 3 months prior to screening, ravulizumab within 6 months prior to screening, or other complement inhibitors within 5 half-lives of the respective agent prior to screening
- Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
- Body weight <40 kilograms at screening visit
- Planned use of any complement inhibitor therapy other than study drugs during the treatment period
- Not meeting meningococcal vaccination requirements and, at a minimum documentation of quadrivalent meningococcal vaccination within 5 years prior to the screening visit and serotype B vaccine within 3 years prior to the screening visit as described in the protocol.
- Any contraindication for receiving Neisseria meningitidis vaccinations (serotypes ACWY and B).
- Unable to take antibiotics for meningococcal prophylaxis (if required by local ravulizumab [Cohort A] or eculizumab [Cohort B] prescribing information, where available, or national guidelines/local practice, or if necessary when administration of the first dose of the quadrivalent meningococcal vaccine [serotype ACWY] or the second dose of the serotype B meningococcal vaccine [when available] is less than 2 weeks prior to study treatment initiation) as described in the protocol
- Any active, ongoing infection or a recent infection requiring ongoing systemic treatment with antibiotics, antivirals, or antifungals within 2 weeks of screening or during the screening period
- Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: Cohort A
Randomized 1:1 |
Administered Intravenous (IV) per the protocol
Другие имена:
Administered IV and subcutaneous (SC) per the protocol
Другие имена:
Administered SC per the protocol
Другие имена:
|
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Экспериментальный: Cohort B
Randomized 1:1 |
Administered IV and subcutaneous (SC) per the protocol
Другие имена:
Administered SC per the protocol
Другие имена:
Administered IV per the protocol
Другие имена:
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Percent change in lactate dehydrogenase (LDH)
Временное ограничение: From baseline to week 26
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Cohort A |
From baseline to week 26
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Transfusion avoidance
Временное ограничение: From post-baseline day 1 through week 26
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Cohort B Not requiring a red blood cell (RBC) transfusion per the protocol |
From post-baseline day 1 through week 26
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Adequate control of hemolysis
Временное ограничение: From week 8 through week 26, inclusive
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Cohort B LDH ≤1.5 × ULN at each visit |
From week 8 through week 26, inclusive
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Maintenance of adequate control of hemolysis
Временное ограничение: From week 8 through week 26, inclusive
|
Cohort A and B LDH ≤1.5 × ULN |
From week 8 through week 26, inclusive
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Breakthrough hemolysis
Временное ограничение: From post-baseline day 1 through week 26
|
Cohort A and B LDH ≥2 × ULN per the protocol |
From post-baseline day 1 through week 26
|
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Adequate control of hemolysis
Временное ограничение: From week 8 through week 26, inclusive
|
Cohort A LDH ≤1.5 × ULN |
From week 8 through week 26, inclusive
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Hemoglobin stabilization
Временное ограничение: From day 1 (post-baseline) through week 26
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Cohort A and B Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per the protocol |
From day 1 (post-baseline) through week 26
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Normalization of LDH
Временное ограничение: Between week 8 through week 26, inclusive
|
Cohort A and B LDH ≤1.0 × ULN per the protocol |
Between week 8 through week 26, inclusive
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Transfusion avoidance
Временное ограничение: Day 1 through week 26
|
Cohort A and B Not requiring an RBC transfusion as per protocol algorithm based on post-baseline hemoglobin values. |
Day 1 through week 26
|
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Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale
Временное ограничение: From baseline to week 26
|
Cohort A and B FACIT-Fatigue Scale is a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related quality of life (QoL) in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue. |
From baseline to week 26
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Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)
Временное ограничение: From baseline to week 26
|
Cohort A and B EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 7 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, sleep and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much." |
From baseline to week 26
|
|
Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30
Временное ограничение: From baseline to week 26
|
Cohort A and B EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 7 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, sleep and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much." |
From baseline to week 26
|
|
Percent change in LDH
Временное ограничение: From baseline to week 26
|
Cohort B |
From baseline to week 26
|
|
Rate of RBC transfused
Временное ограничение: Post-baseline Day 1 through week 26
|
Cohort A and B Per protocol algorithm |
Post-baseline Day 1 through week 26
|
|
Number of units of RBC transfused
Временное ограничение: Post-baseline Day 1 through week 26
|
Cohort A and B Per protocol algorithm |
Post-baseline Day 1 through week 26
|
|
Time to first LDH ≤1.5 × ULN
Временное ограничение: Up to Week 26
|
Cohort A and B |
Up to Week 26
|
|
Time to first LDH ≤1.0 × ULN
Временное ограничение: Up to Week 26
|
Cohort A and B |
Up to Week 26
|
|
Percentage of days with LDH ≤1.5 × ULN
Временное ограничение: Between week 8 and week 26, inclusive
|
Cohort A and B |
Between week 8 and week 26, inclusive
|
|
Change in hemoglobin levels
Временное ограничение: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Incidence and severity of treatment emergent serious adverse events (SAEs)
Временное ограничение: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest
Временное ограничение: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Incidence and severity of TEAEs leading to treatment discontinuation
Временное ограничение: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Change in total CH50
Временное ограничение: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Percent change in total CH50
Временное ограничение: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Concentration of total C5 in plasma
Временное ограничение: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of total pozelimab in serum
Временное ограничение: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of cemdisiran in plasma
Временное ограничение: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of total ravulizumab in serum
Временное ограничение: Up to 34 weeks
|
Cohort A |
Up to 34 weeks
|
|
Concentrations of total eculizumab in serum
Временное ограничение: Up to 30 weeks
|
Cohort B |
Up to 30 weeks
|
|
Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab
Временное ограничение: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Incidence of treatment emergent ADAs to cemdisiran
Временное ограничение: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
Соавторы и исследователи
Спонсор
Следователи
- Директор по исследованиям: Clinical Trial Management, Regeneron Pharmaceuticals
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Действительный)
Завершение исследования (Действительный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- R3918-PNH-2021
- 2020-004486-40 (Номер EudraCT)
- 2023 (Грант/контракт NIH США)
- 2023-509657-31-00 (Ктис)
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
Описание плана IPD
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Сроки обмена IPD
When Regeneron has:
- received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
- made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry),
- the legal authority to share the data, and
- ensured the ability to protect participant privacy.
Критерии совместного доступа к IPD
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
Совместное использование IPD Поддерживающий тип информации
- STUDY_PROTOCOL
- САП
- МКФ
- АНАЛИТИЧЕСКИЙ_КОД
- КСО
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .