Ravulizumab-kontrollert ikke-inferioritetsstudie for å evaluere effektiviteten og sikkerheten til Pozelimab og Cemdisiran kombinasjonsterapi hos voksne pasienter med paroksysmal nattlig hemoglobinuri som er komplementhemmer-naive eller som ikke nylig har mottatt komplementhemmerbehandling (ACCESS-1)
En randomisert, åpen etikett, ravulizumab-kontrollert, ikke-inferioritetsstudie for å evaluere effektiviteten og sikkerheten til kombinasjonsbehandling med Pozelimab og Cemdisiran hos pasienter med paroksysmal nattlig hemoglobinuri som er komplementhemmer-behandling-naive eller som ikke nylig har komplementert inhibitor.
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)
Studieoversikt
Status
Intervensjon / Behandling
Studietype
Registrering (Faktiske)
Fase
- Fase 3
Kontakter og plasseringer
Studiesteder
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São Paulo, Brasil, 08270-070
- Casa de Saude Santa Marcelina
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São Paulo, Brasil, 01321-001
- A Beneficencia Portuguesa de Sao Paulo, BP Mirante
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São Paulo
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Santo André, São Paulo, Brasil, 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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Antioquia
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Medellín, Antioquia, Colombia, 050034
- Hospital Pablo Tobon Uribe
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Central Luzon
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Quezon, Central Luzon, Filippinene, 1011
- St Lukes Medical Center
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California
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Whittier, California, Forente stater, 90602
- The Oncology Institute of Hope & Innovation
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Thessaloniki, Hellas, 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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Aichi-ken
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Nagoya, Aichi-ken, Japan, 466-8650
- Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
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Gifu
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Ōgaki, Gifu, Japan, 503-8502
- Ogaki Municipal Hospital
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Ibaraki
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Tsukuba, Ibaraki, Japan, 305-8576
- University of Tsukuba Hospital
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Osaka
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Moriguchi, Osaka, Japan, 570-8540
- Matsushita Memorial Hospital
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Tokyo
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Shinagawa-ku, Tokyo, Japan, 141-8625
- NTT Medical Center Tokyo
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Amman, Jordan, 11942
- Jordan University Hospital (JUH)
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Beijing Municipality
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Beijing, Beijing Municipality, Kina, 100032
- Peking Union Medical College Hospital
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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, Mexico, 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, Polen, 85-168
- Szpital Uniwersytecki Nr2 Bydgoszcz
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Warsaw, Polen, 02-776
- Institute of Hematology and Transfusion Medicine
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Pomeranian Voivodeship
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Gdansk, Pomeranian Voivodeship, Polen, 80-214
- University Clinical Center Medical University of Gdansk
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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, Spania, 08036
- Hospital Clinic de Barcelona
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Murcia, Spania, 30008
- Hospital General JM Morales Meseguer
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Salamanca, Spania, 37007
- Hospital Clinico Universitario de Salamanca
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Vizcaya
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Bilbao, Vizcaya, Spania, 48013
- Hospital Universitario Basurto
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Leeds, Storbritannia, LS9 7TF
- St James Hospital
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Busan, Sør -Korea, 49241
- Pusan National University Hospital
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Seoul, Sør -Korea, 06351
- Samsung Medical Center
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Seoul, Sør -Korea, 03722
- Severance Hospital
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Seoul, Sør -Korea, 07985
- Ewha Womans University Mokdong Hospital
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Seoul, Sør -Korea, 02841
- Korea University Hospital
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Seoul, Sør -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, Sør -Korea, 16247
- St. Vincent Hospital
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Suwon, Gyeonggi-do, Sør -Korea, 16499
- Ajou University Medical Center
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Namdong-Gu
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Incheon, Namdong-Gu, Sør -Korea, 21565
- Gachon University Gil Medical Center
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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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Bangkok, Thailand, 10330
- King Chulalongkorn Memorial Hospital
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Chiang Mai, Thailand, 50200
- Chaing Mai University
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Khon Kaen, Thailand, 40002
- Faculty of Medicine Khon Kaen University
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Changwat Songkhla
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Hat Yai, Changwat Songkhla, Thailand, 90110
- Clinical Research Center, Faculty of Medicine, Prince of Songkla University
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Istanbul, Tyrkia (Türkiye), 34418
- Istanbul University
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Izmir, Tyrkia (Türkiye), 35100
- Ege University
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Budapest, Ungarn, 1083
- Semmelweis University
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Cohort A
Randomized 1:1 |
Administered Intravenous (IV) per the protocol
Andre navn:
Administered IV and subcutaneous (SC) per the protocol
Andre navn:
Administered SC per the protocol
Andre navn:
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Eksperimentell: Cohort B
Randomized 1:1 |
Administered IV and subcutaneous (SC) per the protocol
Andre navn:
Administered SC per the protocol
Andre navn:
Administered IV per the protocol
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Percent change in lactate dehydrogenase (LDH)
Tidsramme: From baseline to week 26
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Cohort A |
From baseline to week 26
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Transfusion avoidance
Tidsramme: 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
Tidsramme: From week 8 through week 26, inclusive
|
Cohort B LDH ≤1.5 × ULN at each visit |
From week 8 through week 26, inclusive
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Maintenance of adequate control of hemolysis
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
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Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30
Tidsramme: 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
Tidsramme: From baseline to week 26
|
Cohort B |
From baseline to week 26
|
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Rate of RBC transfused
Tidsramme: 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
Tidsramme: 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
Tidsramme: Up to Week 26
|
Cohort A and B |
Up to Week 26
|
|
Time to first LDH ≤1.0 × ULN
Tidsramme: Up to Week 26
|
Cohort A and B |
Up to Week 26
|
|
Percentage of days with LDH ≤1.5 × ULN
Tidsramme: Between week 8 and week 26, inclusive
|
Cohort A and B |
Between week 8 and week 26, inclusive
|
|
Change in hemoglobin levels
Tidsramme: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Incidence and severity of treatment emergent serious adverse events (SAEs)
Tidsramme: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest
Tidsramme: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Incidence and severity of TEAEs leading to treatment discontinuation
Tidsramme: Up to 26 weeks
|
Cohort A and B |
Up to 26 weeks
|
|
Change in total CH50
Tidsramme: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Percent change in total CH50
Tidsramme: From baseline to week 26
|
Cohort A and B |
From baseline to week 26
|
|
Concentration of total C5 in plasma
Tidsramme: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of total pozelimab in serum
Tidsramme: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of cemdisiran in plasma
Tidsramme: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Concentrations of total ravulizumab in serum
Tidsramme: Up to 34 weeks
|
Cohort A |
Up to 34 weeks
|
|
Concentrations of total eculizumab in serum
Tidsramme: Up to 30 weeks
|
Cohort B |
Up to 30 weeks
|
|
Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab
Tidsramme: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
|
Incidence of treatment emergent ADAs to cemdisiran
Tidsramme: Up to 60 weeks
|
Cohort A and B |
Up to 60 weeks
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studieleder: Clinical Trial Management, Regeneron Pharmaceuticals
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- R3918-PNH-2021
- 2020-004486-40 (EudraCT-nummer)
- 2023 (U.S. NIH-stipend/kontrakt)
- 2023-509657-31-00 (Ctis)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
IPD-delingstidsramme
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.
Tilgangskriterier for IPD-deling
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
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
- ICF
- ANALYTIC_CODE
- CSR
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
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