Kontrolowane ravulizumabem badanie non-inferiority mające na celu ocenę skuteczności i bezpieczeństwa leczenia skojarzonego pozelimabem i cedisiranem u dorosłych pacjentów z napadową nocną hemoglobinurią, którzy nie byli wcześniej leczeni inhibitorami dopełniacza lub nie otrzymywali ich ostatnio (ACCESS-1)
Randomizowane, otwarte, kontrolowane ravulizumabem badanie non-inferiority mające na celu ocenę skuteczności i bezpieczeństwa terapii skojarzonej pozelimabem i cemdisiranem u pacjentów z napadową nocną hemoglobinurią, którzy nie byli wcześniej leczeni inhibitorami dopełniacza lub nie otrzymywali ostatnio terapii inhibitorami dopełniacza
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)
Przegląd badań
Status
Warunki
Interwencja / Leczenie
Typ studiów
Zapisy (Rzeczywisty)
Faza
- Faza 3
Kontakty i lokalizacje
Lokalizacje studiów
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São Paulo, Brazylia, 08270-070
- Casa de Saude Santa Marcelina
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São Paulo, Brazylia, 01321-001
- A Beneficencia Portuguesa de Sao Paulo, BP Mirante
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São Paulo
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Santo André, São Paulo, Brazylia, 09060-650
- Centro de Estudos e Pesquisas em Hematologia e Oncologia
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Beijing Municipality
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Beijing, Beijing Municipality, Chiny, 100032
- Peking Union Medical College Hospital
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Central Luzon
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Quezon, Central Luzon, Filipiny, 1011
- St Lukes Medical Center
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Thessaloniki, Grecja, 57010
- George Papanikolaou Hospital
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Barcelona, Hiszpania, 08036
- Hospital Clinic de Barcelona
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Murcia, Hiszpania, 30008
- Hospital General JM Morales Meseguer
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Salamanca, Hiszpania, 37007
- Hospital Clinico Universitario de Salamanca
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Vizcaya
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Bilbao, Vizcaya, Hiszpania, 48013
- Hospital Universitario Basurto
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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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Aichi-ken
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Nagoya, Aichi-ken, Japonia, 466-8650
- Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
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Gifu
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Ōgaki, Gifu, Japonia, 503-8502
- Ogaki Municipal Hospital
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Ibaraki
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Tsukuba, Ibaraki, Japonia, 305-8576
- University of Tsukuba Hospital
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Osaka
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Moriguchi, Osaka, Japonia, 570-8540
- Matsushita Memorial Hospital
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Tokyo
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Shinagawa-ku, Tokyo, Japonia, 141-8625
- NTT Medical Center Tokyo
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Amman, Jordania, 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, Kolumbia, 050034
- Hospital Pablo Tobon Uribe
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Busan, Korea Południowa, 49241
- Pusan National University Hospital
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Seoul, Korea Południowa, 06351
- Samsung Medical Center
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Seoul, Korea Południowa, 03722
- Severance Hospital
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Seoul, Korea Południowa, 07985
- Ewha Womans University Mokdong Hospital
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Seoul, Korea Południowa, 02841
- Korea University Hospital
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Seoul, Korea Południowa, 065791
- Seoul St. Mary's Hospital - The Catholic University of Korea
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Gyeonggi-do
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Suwon, Gyeonggi-do, Korea Południowa, 16247
- St. Vincent Hospital
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Suwon, Gyeonggi-do, Korea Południowa, 16499
- Ajou University Medical Center
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Namdong-Gu
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Incheon, Namdong-Gu, Korea Południowa, 21565
- Gachon University Gil Medical Center
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Pahang
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Kuantan, Pahang, Malezja, 25200
- Hospital Tg Ampuan Afzan
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Sabah
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Kota Kinabalu, Sabah, Malezja, 88586
- Hospital Queen Elizabeth
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Selangor
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Ampang, Selangor, Malezja, 68000
- Hospital Ampang
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Nuevo León
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Monterrey, Nuevo León, Meksyk, 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, Polska, 85-168
- Szpital Uniwersytecki Nr2 Bydgoszcz
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Warsaw, Polska, 02-776
- Institute of Hematology and Transfusion Medicine
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Pomeranian Voivodeship
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Gdansk, Pomeranian Voivodeship, Polska, 80-214
- University Clinical Center Medical University of Gdansk
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Cluj
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Cluj-Napoca, Cluj, Rumunia, 400015
- Ion Chiricuta Oncology Institute
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Dolj
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Craiova, Dolj, Rumunia, 200143
- Municipal Hospital Filantropia
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Mureș County
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Târgu Mureş, Mureș County, Rumunia, 540136
- Targu Mures Clinical County Emergency Hospital
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Singapore, Singapur, 119074
- National University Hospital
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California
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Whittier, California, Stany Zjednoczone, 90602
- The Oncology Institute of Hope & Innovation
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Bangkok, Tajlandia, 10330
- King Chulalongkorn Memorial Hospital
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Chiang Mai, Tajlandia, 50200
- Chaing Mai University
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Khon Kaen, Tajlandia, 40002
- Faculty of Medicine Khon Kaen University
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Changwat Songkhla
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Hat Yai, Changwat Songkhla, Tajlandia, 90110
- Clinical Research Center, Faculty of Medicine, Prince of Songkla University
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Changhua, Tajwan, 500-06
- Changhua Christian Hospital
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Hualien City, Tajwan, 97002
- Hualien Tzu Chi Hospital
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Kaohsiung City, Tajwan, 80756
- Kaohsiung Medical University Hospital
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Taichung, Tajwan, 4070
- Taichung Veterans General Hospital (VGHTC)
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Tainan, Tajwan, 704
- National Cheng Kung University Hospital
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Taipei, Tajwan, 114
- Tri-Service General Hospital
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Taipei, Tajwan, 100229
- National Taiwan University Hospital
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Central Taiwan
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Taichung, Central Taiwan, Tajwan, 40447
- China Medical University Hospital
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Hunan Province
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Taoyuan, Hunan Province, Tajwan, 33305
- Chang Gung Memorial Hospital - Linkou Branch
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Istanbul, Turcja (Türkiye), 34418
- Istanbul University
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Izmir, Turcja (Türkiye), 35100
- Ege University
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Budapest, Węgry, 1083
- Semmelweis University
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Turin, Włochy, 10126
- Hematology Citta della Salute e della Scienza di Torino
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Firenze
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Florence, Firenze, Włochy, 50139
- Aou Careggi
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Roma
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Rome, Roma, Włochy, 00168
- Fondazione Policlinico Universitario A. Gemelli - IRCCS
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Leeds, Zjednoczone Królestwo, LS9 7TF
- St James Hospital
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
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
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Randomizowane
- Model interwencyjny: Przydział równoległy
- Maskowanie: Brak (otwarta etykieta)
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
|---|---|
|
Eksperymentalny: Cohort A
Randomized 1:1 |
Administered Intravenous (IV) per the protocol
Inne nazwy:
Administered IV and subcutaneous (SC) per the protocol
Inne nazwy:
Administered SC per the protocol
Inne nazwy:
|
|
Eksperymentalny: Cohort B
Randomized 1:1 |
Administered IV and subcutaneous (SC) per the protocol
Inne nazwy:
Administered SC per the protocol
Inne nazwy:
Administered IV per the protocol
Inne nazwy:
|
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Percent change in lactate dehydrogenase (LDH)
Ramy czasowe: From baseline to week 26
|
Cohort A |
From baseline to week 26
|
|
Transfusion avoidance
Ramy czasowe: From post-baseline day 1 through week 26
|
Cohort B Not requiring a red blood cell (RBC) transfusion per the protocol |
From post-baseline day 1 through week 26
|
|
Adequate control of hemolysis
Ramy czasowe: From week 8 through week 26, inclusive
|
Cohort B LDH ≤1.5 × ULN at each visit |
From week 8 through week 26, inclusive
|
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Maintenance of adequate control of hemolysis
Ramy czasowe: From week 8 through week 26, inclusive
|
Cohort A and B LDH ≤1.5 × ULN |
From week 8 through week 26, inclusive
|
|
Breakthrough hemolysis
Ramy czasowe: 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
|
|
Adequate control of hemolysis
Ramy czasowe: From week 8 through week 26, inclusive
|
Cohort A LDH ≤1.5 × ULN |
From week 8 through week 26, inclusive
|
|
Hemoglobin stabilization
Ramy czasowe: From day 1 (post-baseline) through week 26
|
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
|
|
Normalization of LDH
Ramy czasowe: 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
|
|
Transfusion avoidance
Ramy czasowe: 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
Ramy czasowe: 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
|
|
Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: From baseline to week 26
|
Cohort B |
From baseline to week 26
|
|
Rate of RBC transfused
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: Up to Week 26
|
Cohort A and B |
Up to Week 26
|
|
Time to first LDH ≤1.0 × ULN
Ramy czasowe: Up to Week 26
|
Cohort A and B |
Up to Week 26
|
|
Percentage of days with LDH ≤1.5 × ULN
Ramy czasowe: Between week 8 and week 26, inclusive
|
Cohort A and B |
Between week 8 and week 26, inclusive
|
|
Change in hemoglobin levels
Ramy czasowe: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Incidence and severity of treatment emergent serious adverse events (SAEs)
Ramy czasowe: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest
Ramy czasowe: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Incidence and severity of TEAEs leading to treatment discontinuation
Ramy czasowe: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Change in total CH50
Ramy czasowe: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Percent change in total CH50
Ramy czasowe: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Concentration of total C5 in plasma
Ramy czasowe: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of total pozelimab in serum
Ramy czasowe: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of cemdisiran in plasma
Ramy czasowe: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of total ravulizumab in serum
Ramy czasowe: Up to 34 weeks
|
Cohort A |
Up to 34 weeks
|
|
Concentrations of total eculizumab in serum
Ramy czasowe: Up to 30 weeks
|
Cohort B |
Up to 30 weeks
|
|
Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab
Ramy czasowe: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Incidence of treatment emergent ADAs to cemdisiran
Ramy czasowe: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
Współpracownicy i badacze
Sponsor
Śledczy
- Dyrektor Studium: Clinical Trial Management, Regeneron Pharmaceuticals
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Zakończenie podstawowe (Rzeczywisty)
Ukończenie studiów (Rzeczywisty)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
- R3918-PNH-2021
- 2020-004486-40 (Numer EudraCT)
- 2023 (Grant/umowa NIH USA)
- 2023-509657-31-00 (Ctis)
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Opis planu IPD
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Ramy czasowe udostępniania 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.
Kryteria dostępu do udostępniania 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 informacji pomocniczych dotyczących udostępniania IPD
- PROTOKÓŁ BADANIA
- SOK ROŚLINNY
- ICF
- ANALITYCZNY_KOD
- CSR
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .