A Study Evaluating The Safety, Pharmacokinetics, and Efficacy Of Crovalimab Versus Eculizumab In Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Interventions
- Registration Number
- NCT04432584
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
A study designed to evaluate the safety of crovalimab with eculizumab in participants with PNH currently treated with complement inhibitors. This study will enroll approximately 190 participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 190
- 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 serotypes A, C, W, and Y < 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 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).
- 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 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 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B (Eculizumab) Eculizumab 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. Arm A (Crovalimab) Crovalimab 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. Arm C (Crovalimab) (Exploratory) Crovalimab 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Injection- Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis) Up to approximately 8 years Percentage of Participants with Clinical Manifestations of Drug-Target-Drug Complex (DTDC) Formation Amongst Those Participants who Switched to Crovalimab Treatment from Eculizumab Treatment or Ravulizumab Treatment Up to approximately 8 years Percentage of Participants with Adverse Events (AEs) and by Severity Up to approximately 8 years Determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5 (CTCAE v5).
Percentage of Participants with Adverse Events (AEs) Leading to Study Drug Discontinuation Up to approximately 8 years
- Secondary Outcome Measures
Name Time Method Serum Concentrations of Ravulizumab at the time of Crovalimab Initiation Baseline Absolute Change in Free Hemoglobin and Haptoglobin (mg/dL) Baseline up to Week 25 Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time Up to approximately 8 years Observed Value in Reticulocyte Count (count/mL) Up to approximately 8 years Change in Reticulocyte Count (count/mL) Baseline up to Week 25 Serum Concentrations of Crovalimab or Eculizumab Over Time Up to approximately 8 years Change Over Time in Free C5 Concentration in Crovalimab-Treated Participants Up to approximately 8 years Percentage of Participants with Anti-Crovalimab Antibodies Up to approximately 8 years Observed Value in Free Hemoglobin and Haptoglobin (mg/dL) Up to approximately 8 years
Trial Locations
- Locations (90)
Institut Paoli Calmette; Service d'Hématologie Clinique
🇫🇷Marseille, France
General Hospital of Athens LAIKO
🇬🇷Athens, Greece
Attikon University General Hospital
🇬🇷Chaidari, Greece
General Hospital of Thessaloniki G. Papanikolaou
🇬🇷Thessaloniki, Greece
Istanbul University Istanbul Medical Faculty; Neurology
🇹🇷Istanbul, Turkey
Marmara University Pendik Training and Research Hospital, Hematology Department
🇹🇷Istanbul, Turkey
Ege University Medical Faculty; Hematology
🇹🇷Izmir, Turkey
Ondokuz Mayis Univ. Med. Fac.
🇹🇷Samsun, Turkey
King'S College Hospital; Haematology
🇬🇧London, United Kingdom
North Estonia Medical Centre Foundation
🇪🇪Tallinn, Estonia
Hopital Claude Huriez - CHU Lille
🇫🇷Lille, France
Universitaetsklinikum Aachen AOeR
🇩🇪Aachen, Germany
ELBLANDKLINIKUM Riesa
🇩🇪Riesa, Germany
The Oncology Institute of Hope and Innovation
🇺🇸Anaheim, California, United States
Carolinas Healthcare System
🇺🇸Charlotte, North Carolina, United States
Nationwide Children's Hospital; Dept. of Pulmonology
🇺🇸Columbus, Ohio, United States
Cliniques Universitaires Saint-Luc; Pharmacy
🇧🇪Bruxelles, Belgium
AZ Delta Campus Westlaan
🇧🇪Roeselare, Belgium
CHU UCL Namur / site Godinne
🇧🇪Yvoir, Belgium
Hospital Universitario Walter Cantidio - UFC
🇧🇷Fortaleza, CE, Brazil
Nucleo de Pesquisa Clinica do Hospital da Crianca
🇧🇷Brasilia, DF, Brazil
Chronos Pesquisa Clinica
🇧🇷Taguatinga, DF, Brazil
Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil
Hospital de Clínicas de Porto Alegre X
🇧🇷Porto Alegre, RS, Brazil
Instituto Joinvilense de Hematologia E Oncologia
🇧🇷Joinville, SC, Brazil
Hospital das Clínicas FMRP-USP
🇧🇷Ribeirao Preto, SP, Brazil
*X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
🇧🇷Santo André, SP, Brazil
Hospital Sírio-Libanês
🇧🇷Sao Paulo, SP, Brazil
Hospital Paulistano
🇧🇷Sao Paulo, SP, Brazil
Beneficencia Portuguesa de Sao Paulo
🇧🇷São Paulo, SP, Brazil
CISSS Chaudière-Appalaches
🇨🇦Levis, Quebec, Canada
Ustav hematologie a krevni transfuze
🇨🇿Praha, Czechia
Fondazione IRCCS CA? Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Lombardia, Italy
The Chinese University of Hong Kong
🇭🇰Shatin, Hong Kong
Azienda Ospedaliera Città della Salute e della Scienza di Torino
🇮🇹Torino, Piemonte, Italy
Semmelweis Egyetem; Belgyogyaszati es Hematologiai Klinika
🇭🇺Budapest, Hungary
St James's Hospital
🇮🇪Dublin, Ireland
Azienda Unita Sanitaria Locale- Ravenna
🇮🇹Ravenna, Emilia-Romagna, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Rome, Lazio, Italy
Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele
🇮🇹Catania, Sicilia, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Florence, Toscana, Italy
Fujita Health University Hospital
🇯🇵Aichi, Japan
Kobe University Hospital; Medical Oncology and Hematology
🇯🇵Hyogo, Japan
Tokushukai Takasago Seibu Hospital
🇯🇵Hyogo, Japan
Ishikawa Prefectural Central Hospital
🇯🇵Ishikawa, Japan
Tokai University Hospital
🇯🇵Kanagawa, Japan
Mie University Hospital
🇯🇵Mie, Japan
Japanese Red Cross Society Suwa Hospital
🇯🇵Nagano, Japan
Nagasaki University Hospital
🇯🇵Nagasaki, Japan
Sasebo City General Hospital
🇯🇵Nagasaki, Japan
National Hospital Organization Okayama Medical Center
🇯🇵Okayama, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Iwate Prefectural Isawa Hospital
🇯🇵Oshu, Japan
NTT Medical Center Tokyo
🇯🇵Tokyo, Japan
Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
Toyama Prefectual Central Hospital
🇯🇵Toyama, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital; Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Amsterdam UMC, Locatie AMC
🇳🇱Amsterdam, Netherlands
Szpital Uniwersytecki nr2 im. dr J. Biziela
🇵🇱Bydgoszcz, Poland
Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii
🇵🇱Gda?sk, Poland
MTZ Clinical Research Powered by Pratia
🇵🇱Warszawa, Poland
Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro
🇵🇹Aveiro, Portugal
Centro Hospitalar do Porto - Hospital de Santo António
🇵🇹Porto, Portugal
King Faisal Specialist Hospital & Research Center
🇸🇦Riyadh, Saudi Arabia
National University Hospital
🇸🇬Singapore, Singapore
Samodzielny Publiczny Szpital Kliniczny nr 1
🇵🇱Lublin, Poland
Centrum Medyczne Pratia Poznan
🇵🇱Skórzewo, Poland
ICO Badalona - Hospital Universitari Germans Trias i Pujol; Hematologia Clinica
🇪🇸Badalona, Barcelona, Spain
Complejo Hospitalario Universitario de Santiago.
🇪🇸Santiago de Compostela, LA Coruña, Spain
Hospital Universitario de Gran Canaria
🇪🇸Las Palmas de Gran Canaria, LAS Palmas, Spain
Hospital de Basurto
🇪🇸Bilbao, Vizcaya, Spain
Hospital U. Central de Asturias
🇪🇸Asturias, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Complejo Hospitalario de Toledo
🇪🇸Toledo, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
Changhua Christian Hospital
🇨🇳Chang Hua, Taiwan
Hualien Tzu Chi Hospital; Hematology and oncology
🇨🇳Hualien City, Taiwan
National Taiwan Universtiy Hospital; Division of Hematology
🇨🇳Taipei, Taiwan
Hacettepe University Medical Faculty; Neurology
🇹🇷Ankara, Turkey
Gaziantep University Medical Faculty Sahinbey Educational Research Hospital; Hematology
🇹🇷Gaziantep, Turkey