A Phase III Study Evaluating The Efficacy And Safety Of Crovalimab Versus Eculizumab In Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors. (COMMODORE 2)
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.
- Willingness and ability to comply with all study visits and procedures.
- Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry.
- LDH level >= 2x ULN at screening (as per local assessment).
- Vaccination against Neisseria meningitidis serotypes A, C, W, < 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 or use contraception during the treatment period and for 10.5 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:
- Current or previous treatment with a complement inhibitor.
- History of allogeneic bone marrow transplantation.
- History of Neisseria meningitidis infection within 6 months prior to screening and up to first study drug administration.
- 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 10.5 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 is greater.
- 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.
- Splenectomy < 6 months before screening.
- Positive for Active Hepatitis B and C infection (HBV/HCV).
- History of or ongoing cryoglobulinemia at screening.
Sites / Locations
- Organizacion Medica de Investigacion (OMI)
- Liverpool Hospital
- Centro Integrado de Oncologia de Curitiba
- Hospital de Clínicas de Porto Alegre X
- *X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
- Beneficencia Portuguesa de Sao Paulo
- Peking Union Medical College Hospital
- Nanfang Hospital, Southern Medical University
- The First Affiliated Hospital, Zhejiang University
- Jiangsu Province Hospital
- Affiliated Hospital of Nantong University; Nephrology
- Huashan Hospital, Fudan University
- Union Hospital Tongji Medical College Huazhong University of Science and Technology
- Hopital Claude Huriez - CHU Lille
- Centre Hospitalier Lyon Sud
- Universitaetsklinkm
- Universitaetsklinikum Ulm
- General Hospital of Thessaloniki G. Papanikolaou
- The Chinese University of Hong Kong; Department of Medicine & Therapeutics
- Sapporo Medical University Hospital
- University of Tsukuba Hospital
- NTT Medical Center Tokyo
- Tokyo Medical University Hospital
- Seoul National University Hospital
- Severance Hospital, Yonsei University Health System
- Asan Medical Center
- Samsung Medical Center
- Vilnius University Hospital Santariskiu Clinics, Public Institution; Cardiology
- Hospital Tengku Ampuan Afzan
- Hospital Raja Permaisuri Bainun
- Hospital Ampang
- Hospital Pulau Pinang
- Global Trial Research Center S.A. de C.V.
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
- Amsterdam UMC, Locatie AMC
- Mary Mediatrix Medical Center
- Philippine General Hospital; Pulmonary Medicine
- St Lukes Medical Center
- Szpital Uniwersytecki nr2 im. dr J. Biziela
- Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii
- Samodzielny Publiczny Szpital Kliniczny nr 1
- Centrum Medyczne Pratia Poznan
- MTZ Clinical Research Powered by Pratia
- Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro
- Centro Hospitalar de Lisboa Central - Hospital D. Estefânia; Pediatrics
- Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
- Centro Hospitalar do Porto - Hospital de Santo António
- Spitalul Universitar de Urgenta Bucuresti
- Spitalul Clinic Municipal Filantropia Craiova
- National University Hospital
- Singapore General Hospital; Department of Haematology
- ICO Badalona - Hospital Universitari Germans Trias i Pujol; Hematologia Clinica
- Hospital Universitario de Gran Canaria Doctor Negrín; Servicio de Hematología
- Hospital de Basurto
- Hospital Clinic de Barcelona
- Hospital San Pedro de Alcantara
- Hospital General Universitario Gregorio Marañon
- Hospital Universitario La Paz
- Hospital Universitario Clinico San Carlos
- Hospital Universitario de Salamanca
- Akademiska Sjukhuset
- Chang Gung Medical Foundation - Kaohsiung; Oncology
- National Taiwan Universtiy Hospital; Division of Hematology
- King Chulalongkorn Memorial Hospital
- Siriraj Hospital
- Maharaj Nakorn Chiang Mai Hospital
- Ondokuz Mayis Univ. Med. Fac.
- Medical Center OK!Clinic+
- Mykolayiv Regional Hospital
- St James University Hospital
- Kings College Hospital; Kings Clinical Research Facility
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Active Comparator
Experimental
Arm A (Crovalimab)
Arm B (Eculizumab)
Arm C (Crovalimab) (Exploratory)
Adult Participants will receive an initial intravenous (IV) loading dose on Week 1 Day 1, followed by 4 weekly crovalimab subcutaneous (SC) doses on Week 1 Day 2, then on Weeks 2, 3 and 4. Maintenance dosing will begin at Week 5 and will continue Q4W (every 4 weeks) thereafter, for a total of at least 24 weeks of study treatment.
Adult Participants will receive initial IV weekly doses for 4 weeks which will be followed by Q2W (every 2 weeks) IV administrations starting on Week 5.
Paediatric 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.