Studie non-inferiority kontrolovaná ravulizumabem k vyhodnocení účinnosti a bezpečnosti kombinované terapie pozelimabem a cemdisiranem u dospělých pacientů s paroxysmální noční hemoglobinurií, kteří dosud neléčili inhibitory komplementu nebo v poslední době neužívali léčbu inhibitory komplementu (ACCESS-1)
Randomizovaná, otevřená, ravulizumabem kontrolovaná, non-inferiorita studie k hodnocení účinnosti a bezpečnosti kombinované terapie pozelimabem a cemdisiranem u pacientů s paroxysmální noční hemoglobinurií, kteří dosud neužívali komplementovou léčbu inhibitory nebo v poslední době nedostávali komplementovou terapii
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)
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 3
Kontakty a umístění
Studijní místa
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São Paulo, Brazílie, 08270-070
- Casa de Saude Santa Marcelina
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São Paulo, Brazílie, 01321-001
- A Beneficencia Portuguesa de Sao Paulo, BP Mirante
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São Paulo
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Santo André, São Paulo, Brazílie, 09060-650
- Centro de Estudos e Pesquisas em Hematologia e Oncologia
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Central Luzon
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Quezon, Central Luzon, Filipíny, 1011
- St Lukes Medical Center
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Jaipur, Indie, 302017
- Bhagwan Mahaveer Cancer Hospital and Research Centre (BMCHRC)
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Kerala
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Kannur, Kerala, Indie, 670103
- Malabar Cancer Center, Kerala
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Kochi, Kerala, Indie, 682041
- Amrita Institute of Medical Sciences (AIMS) and Research Centre Aims
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Maharashtra
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Mumbai, Maharashtra, Indie, 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, Indie, 110085
- Rajiv Gandhi Cancer Institute & Research Center (RGCIRC) - Rohini Campus
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Punjab
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Chandigarh, Punjab, Indie, 708248
- Postgraduate Institute of Medical Education & Research (PGIMER)
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Uttar Pradesh
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Lucknow, Uttar Pradesh, Indie, 226014
- Sanjay Gandhi Postgraduate Institute of Medical Sciences
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Lucknow, Uttar Pradesh, Indie, 226003
- King George Hospital
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Turin, Itálie, 10126
- Hematology Citta della Salute e della Scienza di Torino
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Firenze
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Florence, Firenze, Itálie, 50139
- Aou Careggi
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Roma
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Rome, Roma, Itálie, 00168
- Fondazione Policlinico Universitario A. Gemelli - IRCCS
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Aichi-ken
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Nagoya, Aichi-ken, Japonsko, 466-8650
- Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
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Gifu
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Ōgaki, Gifu, Japonsko, 503-8502
- Ogaki Municipal Hospital
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Ibaraki
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Tsukuba, Ibaraki, Japonsko, 305-8576
- University of Tsukuba Hospital
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Osaka
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Moriguchi, Osaka, Japonsko, 570-8540
- Matsushita Memorial Hospital
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Tokyo
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Shinagawa-ku, Tokyo, Japonsko, 141-8625
- NTT Medical Center Tokyo
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Busan, Jižní Korea, 49241
- Pusan National University Hospital
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Seoul, Jižní Korea, 06351
- Samsung Medical Center
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Seoul, Jižní Korea, 03722
- Severance Hospital
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Seoul, Jižní Korea, 07985
- Ewha Womans University Mokdong Hospital
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Seoul, Jižní Korea, 02841
- Korea University Hospital
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Seoul, Jižní Korea, 065791
- Seoul St. Mary's Hospital - The Catholic University of Korea
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Gyeonggi-do
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Suwon, Gyeonggi-do, Jižní Korea, 16247
- St. Vincent Hospital
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Suwon, Gyeonggi-do, Jižní Korea, 16499
- Ajou University Medical Center
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Namdong-Gu
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Incheon, Namdong-Gu, Jižní Korea, 21565
- Gachon University Gil Medical Center
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Amman, Jordán, 11942
- Jordan University Hospital (JUH)
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Ontario
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Toronto, Ontario, Kanada, M5G 2C4
- Toronto General Hospital
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Antioquia
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Medellín, Antioquia, Kolumbie, 050034
- Hospital Pablo Tobon Uribe
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Pahang
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Kuantan, Pahang, Malajsie, 25200
- Hospital Tg Ampuan Afzan
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Sabah
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Kota Kinabalu, Sabah, Malajsie, 88586
- Hospital Queen Elizabeth
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Selangor
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Ampang, Selangor, Malajsie, 68000
- Hospital Ampang
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Budapest, Maďarsko, 1083
- Semmelweis University
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Nuevo León
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Monterrey, Nuevo León, Mexiko, 64460
- Servicio de Hematologia del Hospital Universitario de la Uanl
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Lima, Peru, 15072
- Clinica San Felipe
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Bydgoszcz, Polsko, 85-168
- Szpital Uniwersytecki Nr2 Bydgoszcz
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Warsaw, Polsko, 02-776
- Institute of Hematology and Transfusion Medicine
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Pomeranian Voivodeship
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Gdansk, Pomeranian Voivodeship, Polsko, 80-214
- University Clinical Center Medical University of Gdansk
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Cluj
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Cluj-Napoca, Cluj, Rumunsko, 400015
- Ion Chiricuta Oncology Institute
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Dolj
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Craiova, Dolj, Rumunsko, 200143
- Municipal Hospital Filantropia
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Mureș County
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Târgu Mureş, Mureș County, Rumunsko, 540136
- Targu Mures Clinical County Emergency Hospital
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Singapore, Singapur, 119074
- National University Hospital
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Leeds, Spojené království, LS9 7TF
- St James Hospital
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California
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Whittier, California, Spojené státy, 90602
- The Oncology Institute of Hope & Innovation
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Changhua, Tchaj-wan, 500-06
- Changhua Christian Hospital
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Hualien City, Tchaj-wan, 97002
- Hualien Tzu Chi Hospital
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Kaohsiung City, Tchaj-wan, 80756
- Kaohsiung Medical University Hospital
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Taichung, Tchaj-wan, 4070
- Taichung Veterans General Hospital (VGHTC)
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Tainan, Tchaj-wan, 704
- National Cheng Kung University Hospital
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Taipei, Tchaj-wan, 114
- Tri-Service General Hospital
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Taipei, Tchaj-wan, 100229
- National Taiwan University Hospital
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Central Taiwan
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Taichung, Central Taiwan, Tchaj-wan, 40447
- China Medical University Hospital
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Hunan Province
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Taoyuan, Hunan Province, Tchaj-wan, 33305
- Chang Gung Memorial Hospital - Linkou Branch
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Bangkok, Thajsko, 10330
- King Chulalongkorn Memorial Hospital
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Chiang Mai, Thajsko, 50200
- Chaing Mai University
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Khon Kaen, Thajsko, 40002
- Faculty of Medicine Khon Kaen University
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Changwat Songkhla
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Hat Yai, Changwat Songkhla, Thajsko, 90110
- Clinical Research Center, Faculty of Medicine, Prince of Songkla University
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Istanbul, Turecko (Türkiye), 34418
- Istanbul University
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Izmir, Turecko (Türkiye), 35100
- Ege University
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Beijing Municipality
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Beijing, Beijing Municipality, Čína, 100032
- Peking Union Medical College Hospital
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Thessaloniki, Řecko, 57010
- George Papanikolaou Hospital
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Barcelona, Španělsko, 08036
- Hospital Clinic de Barcelona
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Murcia, Španělsko, 30008
- Hospital General JM Morales Meseguer
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Salamanca, Španělsko, 37007
- Hospital Clinico Universitario de Salamanca
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Vizcaya
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Bilbao, Vizcaya, Španělsko, 48013
- Hospital Universitario Basurto
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: Cohort A
Randomized 1:1 |
Administered Intravenous (IV) per the protocol
Ostatní jména:
Administered IV and subcutaneous (SC) per the protocol
Ostatní jména:
Administered SC per the protocol
Ostatní jména:
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Experimentální: Cohort B
Randomized 1:1 |
Administered IV and subcutaneous (SC) per the protocol
Ostatní jména:
Administered SC per the protocol
Ostatní jména:
Administered IV per the protocol
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Percent change in lactate dehydrogenase (LDH)
Časové okno: From baseline to week 26
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Cohort A |
From baseline to week 26
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Transfusion avoidance
Časové okno: 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
Časové okno: 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
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Maintenance of adequate control of hemolysis
Časové okno: From week 8 through week 26, inclusive
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Cohort A and B LDH ≤1.5 × ULN |
From week 8 through week 26, inclusive
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Breakthrough hemolysis
Časové okno: From post-baseline day 1 through week 26
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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
Časové okno: From week 8 through week 26, inclusive
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Cohort A LDH ≤1.5 × ULN |
From week 8 through week 26, inclusive
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Hemoglobin stabilization
Časové okno: 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
Časové okno: Between week 8 through week 26, inclusive
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Cohort A and B LDH ≤1.0 × ULN per the protocol |
Between week 8 through week 26, inclusive
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Transfusion avoidance
Časové okno: Day 1 through week 26
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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
Časové okno: From baseline to week 26
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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)
Časové okno: From baseline to week 26
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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
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Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30
Časové okno: From baseline to week 26
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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
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Percent change in LDH
Časové okno: From baseline to week 26
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Cohort B |
From baseline to week 26
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Rate of RBC transfused
Časové okno: Post-baseline Day 1 through week 26
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Cohort A and B Per protocol algorithm |
Post-baseline Day 1 through week 26
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Number of units of RBC transfused
Časové okno: Post-baseline Day 1 through week 26
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Cohort A and B Per protocol algorithm |
Post-baseline Day 1 through week 26
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Time to first LDH ≤1.5 × ULN
Časové okno: Up to Week 26
|
Cohort A and B |
Up to Week 26
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Time to first LDH ≤1.0 × ULN
Časové okno: Up to Week 26
|
Cohort A and B |
Up to Week 26
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Percentage of days with LDH ≤1.5 × ULN
Časové okno: Between week 8 and week 26, inclusive
|
Cohort A and B |
Between week 8 and week 26, inclusive
|
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Change in hemoglobin levels
Časové okno: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
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Incidence and severity of treatment emergent serious adverse events (SAEs)
Časové okno: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
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Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest
Časové okno: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
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Incidence and severity of TEAEs leading to treatment discontinuation
Časové okno: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Change in total CH50
Časové okno: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Percent change in total CH50
Časové okno: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Concentration of total C5 in plasma
Časové okno: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of total pozelimab in serum
Časové okno: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
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Concentrations of cemdisiran in plasma
Časové okno: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of total ravulizumab in serum
Časové okno: Up to 34 weeks
|
Cohort A |
Up to 34 weeks
|
|
Concentrations of total eculizumab in serum
Časové okno: Up to 30 weeks
|
Cohort B |
Up to 30 weeks
|
|
Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab
Časové okno: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Incidence of treatment emergent ADAs to cemdisiran
Časové okno: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Ředitel studie: Clinical Trial Management, Regeneron Pharmaceuticals
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- R3918-PNH-2021
- 2020-004486-40 (Číslo EudraCT)
- 2023 (Grant/smlouva NIH USA)
- 2023-509657-31-00 (Ctis)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Časový rámec sdílení 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.
Kritéria přístupu pro sdílení 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
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
- ICF
- ANALYTIC_CODE
- CSR
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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