Studio di non inferiorità controllato con ravulizumab per valutare l'efficacia e la sicurezza della terapia di associazione con pozelimab e cemdisiran in pazienti adulti con emoglobinuria parossistica notturna che sono naive al trattamento con inibitori del complemento o che non hanno ricevuto di recente una terapia con inibitori del complemento (ACCESS-1)
Uno studio di non inferiorità randomizzato, in aperto, controllato con Ravulizumab per valutare l'efficacia e la sicurezza della terapia di combinazione con Pozelimab e Cemdisiran in pazienti con emoglobinuria parossistica notturna che sono naive al trattamento con inibitori del complemento o che non hanno ricevuto di recente una terapia con inibitori del complemento
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)
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 3
Contatti e Sedi
Luoghi di studio
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São Paulo, Brasile, 08270-070
- Casa de Saude Santa Marcelina
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São Paulo, Brasile, 01321-001
- A Beneficencia Portuguesa de Sao Paulo, BP Mirante
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São Paulo
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Santo André, São Paulo, Brasile, 09060-650
- Centro de Estudos e Pesquisas em Hematologia e Oncologia
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Ontario
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Toronto, Ontario, Canada, M5G 2C4
- Toronto General Hospital
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Beijing Municipality
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Beijing, Beijing Municipality, Cina, 100032
- Peking Union Medical College Hospital
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Antioquia
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Medellín, Antioquia, Colombia, 050034
- Hospital Pablo Tobon Uribe
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Busan, Corea del Sud, 49241
- Pusan National University Hospital
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Seoul, Corea del Sud, 06351
- Samsung Medical Center
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Seoul, Corea del Sud, 03722
- Severance Hospital
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Seoul, Corea del Sud, 07985
- Ewha Womans University Mokdong Hospital
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Seoul, Corea del Sud, 02841
- Korea University Hospital
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Seoul, Corea del Sud, 065791
- Seoul St. Mary's Hospital - The Catholic University of Korea
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Gyeonggi-do
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Suwon, Gyeonggi-do, Corea del Sud, 16247
- St. Vincent Hospital
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Suwon, Gyeonggi-do, Corea del Sud, 16499
- Ajou University Medical Center
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Namdong-Gu
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Incheon, Namdong-Gu, Corea del Sud, 21565
- Gachon University Gil Medical Center
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Central Luzon
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Quezon, Central Luzon, Filippine, 1011
- St Lukes Medical Center
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Aichi-ken
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Nagoya, Aichi-ken, Giappone, 466-8650
- Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
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Gifu
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Ōgaki, Gifu, Giappone, 503-8502
- Ogaki Municipal Hospital
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Ibaraki
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Tsukuba, Ibaraki, Giappone, 305-8576
- University of Tsukuba Hospital
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Osaka
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Moriguchi, Osaka, Giappone, 570-8540
- Matsushita Memorial Hospital
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Tokyo
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Shinagawa-ku, Tokyo, Giappone, 141-8625
- NTT Medical Center Tokyo
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Amman, Giordania, 11942
- Jordan University Hospital (JUH)
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Thessaloniki, Grecia, 57010
- George Papanikolaou Hospital
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Jaipur, India, 302017
- Bhagwan Mahaveer Cancer Hospital and Research Centre (BMCHRC)
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Kerala
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Kannur, Kerala, India, 670103
- Malabar Cancer Center, Kerala
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Kochi, Kerala, India, 682041
- Amrita Institute of Medical Sciences (AIMS) and Research Centre Aims
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Maharashtra
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Mumbai, Maharashtra, India, 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, India, 110085
- Rajiv Gandhi Cancer Institute & Research Center (RGCIRC) - Rohini Campus
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Punjab
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Chandigarh, Punjab, India, 708248
- Postgraduate Institute of Medical Education & Research (PGIMER)
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Uttar Pradesh
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Lucknow, Uttar Pradesh, India, 226014
- Sanjay Gandhi Postgraduate Institute of Medical Sciences
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Lucknow, Uttar Pradesh, India, 226003
- King George Hospital
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Turin, Italia, 10126
- Hematology Citta della Salute e della Scienza di Torino
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Firenze
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Florence, Firenze, Italia, 50139
- Aou Careggi
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Roma
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Rome, Roma, Italia, 00168
- Fondazione Policlinico Universitario A. Gemelli - IRCCS
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Pahang
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Kuantan, Pahang, Malaysia, 25200
- Hospital Tg Ampuan Afzan
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Sabah
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Kota Kinabalu, Sabah, Malaysia, 88586
- Hospital Queen Elizabeth
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Selangor
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Ampang, Selangor, Malaysia, 68000
- Hospital Ampang
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Nuevo León
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Monterrey, Nuevo León, Messico, 64460
- Servicio de Hematologia del Hospital Universitario de la Uanl
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Lima, Perù, 15072
- Clinica San Felipe
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Bydgoszcz, Polonia, 85-168
- Szpital Uniwersytecki Nr2 Bydgoszcz
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Warsaw, Polonia, 02-776
- Institute of Hematology and Transfusion Medicine
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Pomeranian Voivodeship
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Gdansk, Pomeranian Voivodeship, Polonia, 80-214
- University Clinical Center Medical University of Gdansk
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Leeds, Regno Unito, LS9 7TF
- St James Hospital
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Cluj
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Cluj-Napoca, Cluj, Romania, 400015
- Ion Chiricuta Oncology Institute
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Dolj
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Craiova, Dolj, Romania, 200143
- Municipal Hospital Filantropia
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Mureș County
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Târgu Mureş, Mureș County, Romania, 540136
- Targu Mures Clinical County Emergency Hospital
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Singapore, Singapore, 119074
- National University Hospital
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Barcelona, Spagna, 08036
- Hospital Clinic de Barcelona
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Murcia, Spagna, 30008
- Hospital General JM Morales Meseguer
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Salamanca, Spagna, 37007
- Hospital Clinico Universitario de Salamanca
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Vizcaya
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Bilbao, Vizcaya, Spagna, 48013
- Hospital Universitario Basurto
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California
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Whittier, California, Stati Uniti, 90602
- The Oncology Institute of Hope & Innovation
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Bangkok, Tailandia, 10330
- King Chulalongkorn Memorial Hospital
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Chiang Mai, Tailandia, 50200
- Chaing Mai University
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Khon Kaen, Tailandia, 40002
- Faculty of Medicine Khon Kaen University
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Changwat Songkhla
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Hat Yai, Changwat Songkhla, Tailandia, 90110
- Clinical Research Center, Faculty of Medicine, Prince of Songkla University
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Changhua, Taiwan, 500-06
- Changhua Christian Hospital
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Hualien City, Taiwan, 97002
- Hualien Tzu Chi Hospital
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Kaohsiung City, Taiwan, 80756
- Kaohsiung Medical University Hospital
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Taichung, Taiwan, 4070
- Taichung Veterans General Hospital (VGHTC)
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Tainan, Taiwan, 704
- National Cheng Kung University Hospital
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Taipei, Taiwan, 114
- Tri-Service General Hospital
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Taipei, Taiwan, 100229
- National Taiwan University Hospital
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Central Taiwan
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Taichung, Central Taiwan, Taiwan, 40447
- China Medical University Hospital
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Hunan Province
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Taoyuan, Hunan Province, Taiwan, 33305
- Chang Gung Memorial Hospital - Linkou Branch
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Istanbul, Turchia (Türkiye), 34418
- Istanbul University
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Izmir, Turchia (Türkiye), 35100
- Ege University
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Budapest, Ungheria, 1083
- Semmelweis University
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: Cohort A
Randomized 1:1 |
Administered Intravenous (IV) per the protocol
Altri nomi:
Administered IV and subcutaneous (SC) per the protocol
Altri nomi:
Administered SC per the protocol
Altri nomi:
|
|
Sperimentale: Cohort B
Randomized 1:1 |
Administered IV and subcutaneous (SC) per the protocol
Altri nomi:
Administered SC per the protocol
Altri nomi:
Administered IV per the protocol
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Percent change in lactate dehydrogenase (LDH)
Lasso di tempo: From baseline to week 26
|
Cohort A |
From baseline to week 26
|
|
Transfusion avoidance
Lasso di tempo: 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
|
|
Adequate control of hemolysis
Lasso di tempo: From week 8 through week 26, inclusive
|
Cohort B LDH ≤1.5 × ULN at each visit |
From week 8 through week 26, inclusive
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Maintenance of adequate control of hemolysis
Lasso di tempo: From week 8 through week 26, inclusive
|
Cohort A and B LDH ≤1.5 × ULN |
From week 8 through week 26, inclusive
|
|
Breakthrough hemolysis
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
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Normalization of LDH
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: From baseline to week 26
|
Cohort B |
From baseline to week 26
|
|
Rate of RBC transfused
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: Up to Week 26
|
Cohort A and B |
Up to Week 26
|
|
Time to first LDH ≤1.0 × ULN
Lasso di tempo: Up to Week 26
|
Cohort A and B |
Up to Week 26
|
|
Percentage of days with LDH ≤1.5 × ULN
Lasso di tempo: Between week 8 and week 26, inclusive
|
Cohort A and B |
Between week 8 and week 26, inclusive
|
|
Change in hemoglobin levels
Lasso di tempo: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Incidence and severity of treatment emergent serious adverse events (SAEs)
Lasso di tempo: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest
Lasso di tempo: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Incidence and severity of TEAEs leading to treatment discontinuation
Lasso di tempo: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Change in total CH50
Lasso di tempo: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Percent change in total CH50
Lasso di tempo: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Concentration of total C5 in plasma
Lasso di tempo: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of total pozelimab in serum
Lasso di tempo: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of cemdisiran in plasma
Lasso di tempo: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of total ravulizumab in serum
Lasso di tempo: Up to 34 weeks
|
Cohort A |
Up to 34 weeks
|
|
Concentrations of total eculizumab in serum
Lasso di tempo: Up to 30 weeks
|
Cohort B |
Up to 30 weeks
|
|
Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab
Lasso di tempo: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Incidence of treatment emergent ADAs to cemdisiran
Lasso di tempo: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
Collaboratori e investigatori
Sponsor
Investigatori
- Direttore dello studio: Clinical Trial Management, Regeneron Pharmaceuticals
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- R3918-PNH-2021
- 2020-004486-40 (Numero EudraCT)
- 2023 (Sovvenzione/contratto NIH degli Stati Uniti)
- 2023-509657-31-00 (Ctis)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Periodo di condivisione 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.
Criteri di accesso alla condivisione 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
Tipo di informazioni di supporto alla condivisione IPD
- STUDIO_PROTOCOLLO
- LINFA
- ICF
- CODICE_ANALITICO
- RSI
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .