A Study Evaluating The Safety, Pharmacokinetics, and Efficacy Of Crovalimab Versus Eculizumab In Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors (COMMODORE 1)
Paroxysmal Nocturnal Hemoglobinuria
About this trial
This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria
Eligibility Criteria
Inclusion Criteria:
- Body weight >= 40 kg at screening.
- Treated with eculizumab or ravulizumab for PNH for at least 3 months prior to Day 1.
- Lactate Dehydrogenase Levels =< 2x the upper limit of normal (ULN) at screening.
- Willingness and ability to comply with all study visits and procedures.
- Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry.
- Vaccination against Neisseria meningitidis < 3 years prior to initiation of study treatment; or, if not previously done, vaccination administered no later than one week after the first drug administration.
- Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 6 months after the final dose of crovalimab or for 3 months after the final dose of eculizumab (or longer if required by the local product label).
Exclusion Criteria:
- History of allogeneic bone marrow transplantation.
- History of myelodysplastic syndrome with Revised International Prognostic Scoring System (IPSS-R) prognostic risk categories of intermediate, high and very high.
- Pregnant or breastfeeding, or intending to become pregnant during the study, within 6 months after the final dose of crovalimab, or 3 months after the final dose of eculizumab (or longer if required by the local product label).
- Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within 5 half-lives of that investigational product, whichever was greater: participants enrolled in an eculizumab or ravulizumab interventional study are eligible provided they fulfill eligibility (e.g., are willing and able to comply with the study assessments) and stop their participation in current trial before randomisation/enrolment.
- Positive for Active Hepatitis B and C infection (HBV/HCV).
- Concurrent disease, treatment, procedure, or surgery or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose any additional risk for the participant, or would, in the opinion of the investigator, preclude the participant's safe participation in and completion of the study.
- History of or ongoing cryoglobulinemia at screening.
Sites / Locations
- The Oncology Institute of Hope and Innovation
- David Geffen School of Medicine UCLARecruiting
- Indiana Blood & Marrow Transplantation, LLCRecruiting
- Henry Ford HospitalRecruiting
- Carolinas Healthcare SystemRecruiting
- Nationwide Children's Hospital; Dept. of PulmonologyRecruiting
- Cook Childrens Medical CenterRecruiting
- University of Texas Health Science Center at San AntonioRecruiting
- Liverpool HospitalRecruiting
- Westmead HospitalRecruiting
- Royal Perth HospitalRecruiting
- Cliniques Universitaires Saint-Luc; PharmacyRecruiting
- AZ Delta Campus WestlaanRecruiting
- CHU UCL Namur / site GodinneRecruiting
- Hospital Universitario Walter Cantidio - UFCRecruiting
- Nucleo de Pesquisa Clinica do Hospital da CriancaRecruiting
- Chronos Pesquisa ClinicaRecruiting
- Elo Clinical Research
- Centro Integrado de Oncologia de CuritibaRecruiting
- Hrpc - Health Clinical Research Representation - Eireli
- Santa Casa de Misericordia de Porto AlegreRecruiting
- Hospital de Clínicas de Porto Alegre X
- Instituto Joinvilense de Hematologia E OncologiaRecruiting
- Fundação Doutor Amaral CarvalhoRecruiting
- Hospital das Clínicas FMRP-USP
- *X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e OncologiaRecruiting
- Hospital Sírio-Libanês
- Hospital PaulistanoRecruiting
- Beneficencia Portuguesa de Sao PauloRecruiting
- CISSS Chaudière-AppalachesRecruiting
- Fundacion Santa Fe de Bogota
- Ustav hematologie a krevni transfuzeRecruiting
- North Estonia Medical Centre FoundationRecruiting
- Hopital Claude Huriez - CHU LilleRecruiting
- Institut Paoli Calmette; Service d'Hématologie CliniqueRecruiting
- CHU Rennes - Hopital Pontchaillou; Service d'Hémostase BiocliniqueRecruiting
- Universitaetsklinikum Aachen AOeRRecruiting
- UniversitaetsklinikumRecruiting
- ELBLANDKLINIKUM RiesaRecruiting
- Universitaetsklinikum UlmRecruiting
- University General Hospital of AlexandroupolisRecruiting
- General Hospital of Athens LAIKORecruiting
- Attikon University General HospitalRecruiting
- University General Hospital of LarissaRecruiting
- General Hospital of Thessaloniki G. PapanikolaouRecruiting
- The Chinese University of Hong KongRecruiting
- Semmelweis EgyetemRecruiting
- St James's HospitalRecruiting
- Azienda Ospedaliera San Giuseppe Moscati
- Azienda Unita Sanitaria Locale- RavennaRecruiting
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSRecruiting
- Fondazione IRCCS CA? Granda Ospedale Maggiore PoliclinicoRecruiting
- Azienda Ospedaliera Città della Salute e della Scienza di TorinoRecruiting
- Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele
- Azienda Ospedaliera Universitaria CareggiRecruiting
- Fujita Health University HospitalRecruiting
- Fukushima Medical University HospitalRecruiting
- Sapporo Medical University Hospital
- Kobe University Hospital; Medical Oncology and HematologyRecruiting
- Tokushukai Takasago Seibu HospitalRecruiting
- University of Tsukuba Hospital
- Ishikawa Prefectural Central Hospital
- Tokai University HospitalRecruiting
- Mie University Hospital
- Japanese Red Cross Society Suwa Hospital
- Nagasaki University HospitalRecruiting
- Sasebo City General HospitalRecruiting
- National Hospital Organization Okayama Medical Center
- Osaka University HospitalRecruiting
- Iwate Prefectural Isawa Hospital
- NTT Medical Center TokyoRecruiting
- Tokyo Medical University Hospital
- Toyama Prefectual Central Hospital
- Seoul National University HospitalRecruiting
- Severance Hospital; Yonsei University Health SystemRecruiting
- Asan Medical Center
- Samsung Medical CenterRecruiting
- Ulsan University HospitalRecruiting
- Amsterdam UMC, Locatie AMCRecruiting
- Szpital Uniwersytecki nr2 im. dr J. BizielaRecruiting
- Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i TransplantologiiRecruiting
- SPZOZ Szpital Uniw W KrakowieRecruiting
- Samodzielny Publiczny Szpital Kliniczny nr 1Recruiting
- Centrum Medyczne Pratia PoznanRecruiting
- MTZ Clinical Research Powered by PratiaRecruiting
- Centro Hospitalar do Porto - Hospital de Santo AntónioRecruiting
- King Faisal Specialist Hospital & Research CenterRecruiting
- National University HospitalRecruiting
- ICO Badalona - Hospital Universitari Germans Trias i Pujol; Hematologia ClinicaRecruiting
- Hospital Sant Joan De DeuRecruiting
- Complejo Hospitalario Universitario de Santiago.Recruiting
- Hospital Universitario de Gran CanariaRecruiting
- Hospital de BasurtoRecruiting
- Hospital U. Central de AsturiasRecruiting
- Hospital Universitari Vall d'HebronRecruiting
- Hospital Clinic de Barcelona
- Hospital San Pedro de AlcantaraRecruiting
- Hospital General Universitario Gregorio MarañonRecruiting
- Hospital Universitario Clinico San CarlosRecruiting
- Hospital Regional Universitario de MalagaRecruiting
- Hospital Universitario de SalamancaRecruiting
- Hospital Universitario Virgen del RocioRecruiting
- Complejo Hospitalario de ToledoRecruiting
- Hospital Universitari i Politecnic La Fe de ValenciaRecruiting
- Hospital Universitario Miguel ServetRecruiting
- Akademiska SjukhusetRecruiting
- Changhua Christian HospitalRecruiting
- Hualien Tzu Chi Hospital; Hematology and oncologyRecruiting
- Chi Mei Medical Center Liou Ying Campus
- National Taiwan Universtiy Hospital; Division of HematologyRecruiting
- MacKay Memorial Hospital; Hematology and oncology
- Hacettepe University Medical Faculty; NeurologyRecruiting
- Gaziantep University Medical Faculty Sahinbey Educational Research Hospital; HematologyRecruiting
- Istanbul University Istanbul Medical Faculty; NeurologyRecruiting
- Marmara University Pendik Training and Research Hospital, Hematology DepartmentRecruiting
- Ege University Medical Faculty; HematologyRecruiting
- Ondokuz Mayis Univ. Med. Fac.Recruiting
- King'S College Hospital; HaematologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Active Comparator
Experimental
Arm A (Crovalimab)
Arm B (Eculizumab)
Arm C (Crovalimab) (Exploratory)
Participants will receive a loading series of crovalimab comprised of an intravenous (IV) dose on Day 1, followed by weekly crovalimab subcutaneous (SC) doses for 4 weeks on Week 1 Day 2, then on Weeks 2, 3, and 4. Maintenance SC dosing will begin at Week 5 and will continue Q4W (every 4 weeks) thereafter for a total of 24 weeks of study treatment. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.
Participants will receive an approved maintenance dose of eculizumab starting on Day 1 and Q2W (every 2 weeks) thereafter for a total of 24 weeks of study treatment. After 24 weeks of study eculizumab treatment, participants will have the option to switch to crovalimab or to discontinue from the study after completion of 10 weeks of safety follow-up.
Participants will receive a loading series of Crovalimab comprised of an IV dose on Week 1 Day 1, followed by weekly crovalimab SC doses for 4 weeks on Week 1 (Day 2) then on Weeks 2, 3, and 4. Maintenance SC dosing will begin at Week 5 and will be administered Q4W thereafter. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.