Clinical trial • Phase III • Haematology
CROVALIMAB for Paroxysmal nocturnal hemoglobinuria
Phase III trial of CROVALIMAB for Paroxysmal nocturnal hemoglobinuria.
Overview
- Trial Therapeutic Area
- Haematology
- Trial Disease
- Paroxysmal nocturnal hemoglobinuria
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 21-05-2024
- First CTIS Authorization Date
- 28-06-2024
Trial design
Randomised, open-label, eculizumab (eculizumab) - concentrate for solution for infusion; active substance eculizumab; intravenous route; product data lists max daily dose amount 900 mg (dosing schedule not specified in ctis json).-controlled Phase III trial in Sweden, France, Lithuania and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Eculizumab (ECULIZUMAB) - concentrate for solution for infusion; active substance ECULIZUMAB; intravenous route; product data lists max daily dose amount 900 mg (dosing schedule not specified in CTIS JSON).
- Target Sample Size
- 167
- Trial Duration For Participant
- 284
Eligibility
Recruits 167 paediatric patients.
- Vulnerable Population
- Vulnerable population selected. The trial includes adolescents and pediatric patients (documents and ICFs provided for minors). Assent and parental/guardian consent processes are used: parental/parental ICFs and infant authorization forms are provided; assent forms exist for age groups (e.g. 7-11 years, 12-14/12-16 years, 15-17 years). Country-specific subject information and ICF documents are provided in multiple languages (versions for EN, FR, ES, PT, NL, PL, LT, SE, RO, DE appear among submitted ICFs).
Inclusion criteria
- {"criterion_text":"- Body weight ≥ 40 kg (pediatric patients with body weight < 40 kg)\n- Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry evaluation of WBCs\n- LDH level ≥2 x ULN at screening (as per local assessment)\n- Platelet count >= 30,000/mm*3 at screening without transfusion support within 7 days of lab testing\n- ANC > 500/micro L at screening\n- For female patients of childbearing potential: agreement to remain abstinent or use contraception"}
Exclusion criteria
- {"criterion_text":"- Current or previous treatment with a complement inhibitor\n- History of allogeneic bone marrow transplantation\n- History of Neisseria meningitidis infection within 6 months prior to screening and up to first study drug administration\n- History of myelodysplastic syndrome with Revised International Prognostic Scoring System (IPSS-R) prognostic risk categories of intermediate, high and very high\n- Splenectomy <= 6 months prior to screening\n- History of or ongoing cryoglobulinemia at screening"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 1. Proportion of patients who achieve transfusion avoidance","definition_or_measurement_approach":"Proportion of patients meeting the criterion of transfusion avoidance (binary outcome assessed per patient during the relevant evaluation period)."}
- {"endpoint_text":"- 2. Proportion of patients with hemolysis control, measured by LDH <=1.5×ULN","definition_or_measurement_approach":"Proportion of patients with lactate dehydrogenase (LDH) ≤ 1.5 × upper limit of normal (ULN) (LDH measured by local assessment)."}
Secondary endpoints
- {"endpoint_text":"- 1. Proportion of patients with breakthrough hemolysis","definition_or_measurement_approach":"Proportion of patients experiencing breakthrough hemolysis (as defined in protocol; no additional detail in CTIS JSON)."}
- {"endpoint_text":"- 2. Proportion of patients with stabilization of hemoglobin","definition_or_measurement_approach":"Proportion of patients achieving haemoglobin stabilization (exact protocol definition not included in JSON)."}
- {"endpoint_text":"- 3. Mean change in fatigue, as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue","definition_or_measurement_approach":"Mean change from baseline in FACIT-Fatigue score (instrument: FACIT-Fatigue)."}
- {"endpoint_text":"- 4. Incidence and severity of adverse events","definition_or_measurement_approach":"Incidence and severity graded by standard AE reporting (no additional definition in JSON)."}
- {"endpoint_text":"- 5. Change from baseline in targeted vital signs","definition_or_measurement_approach":"Change from baseline in pre-specified vital signs (details not provided in JSON)."}
- {"endpoint_text":"- 6. Change from baseline in targeted clinical laboratory test results","definition_or_measurement_approach":"Change from baseline in specified clinical laboratory parameters (details not provided in JSON)."}
- {"endpoint_text":"- 7. Incidence and severity of injection-site reactions, infusion-related reactions, hypersensitivity, and infections","definition_or_measurement_approach":"Incidence and severity of listed event types (standard AE reporting)."}
- {"endpoint_text":"- 8. Incidence of adverse events leading to study drug discontinuation","definition_or_measurement_approach":"Incidence of AEs that result in permanent discontinuation of study drug (per investigator assessment/reporting)."}
- {"endpoint_text":"- 9. Incidence and severity of clinical manifestations of drug-target-drug complex formation in patients who switched to crovalimab treatment from eculizumab treatment","definition_or_measurement_approach":"Incidence and severity of clinical manifestations attributed to drug-target-drug complex formation in switch patients (protocol-defined assessments; not detailed in JSON)."}
- {"endpoint_text":"- 10. Serum concentration of crovalimab and eculizumab","definition_or_measurement_approach":"Measured serum concentrations of crovalimab and eculizumab (PK assays)."}
- {"endpoint_text":"- 11. Prevalence and incidence of anti-drug antibodies (ADAs) to crovalimab","definition_or_measurement_approach":"Assessment of presence and incidence of anti-drug antibodies (ADA assays)."}
- {"endpoint_text":"- 12. Change over time in pharmacodynamic biomarkers","definition_or_measurement_approach":"Longitudinal assessment of predefined pharmacodynamic biomarkers (details not provided in JSON)."}
- {"endpoint_text":"- 13. Change over time in free C5 concentration in crovalimab-treated patients","definition_or_measurement_approach":"Longitudinal measurement of free C5 concentration in serum in crovalimab-treated participants."}
- {"endpoint_text":"- 14. Observed value and absolute change from baseline to week 25 in parameters reflecting hemolysis","definition_or_measurement_approach":"Observed values and absolute change from baseline to Week 25 for hemolysis-related parameters (e.g., LDH and related labs; specific parameters not listed in JSON)."}
Recruitment
- Registry Or Advocacy Recruitment
- True, Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi (listed as a third-party patient organisation/association)
- Planned Sample Size
- 167
- Recruitment Window Months
- 94
- Consent Approach
- Informed consent obtained from adult participants. For minors/adolescents, parental/guardian consent is used together with age-appropriate assent/infant authorization forms. Multiple country-specific ICFs and assent/parental/infant authorization documents submitted (examples: Parental ICF, Assent ICF 7-11 yrs, Assent ICF 12-14/12-16 yrs, Assent 15-17 yrs, Infant Authorization Form). Documents available in multiple language versions across countries (EN, FR, ES, PT, NL, PL, LT, SE, RO, DE as evidenced by submitted ICFs).
Geography
- Total Number Of Sites
- 22
- Total Number Of Participants
- 42
Sweden
- Earliest CTIS Part Ii Submission Date
- 12-06-2024
- Latest Decision Or Authorization Date
- 28-06-2024
- Processing Time Days
- 16
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Uppsala University Hospital
- Department Name
- Dept. of Hematology
- Principal Investigator Name
- Martin Hoglund
- Principal Investigator Email
- martin.hoglund@medsci.uu.se
- Contact Person Name
- Martin Hoglund
- Contact Person Email
- martin.hoglund@medsci.uu.se
France
- Earliest CTIS Part Ii Submission Date
- 12-06-2024
- Latest Decision Or Authorization Date
- 28-06-2024
- Processing Time Days
- 16
- Number Of Sites
- 2
- Number Of Participants
- 2
Sites
- Site Name
- Centre Hospitalier Universitaire De Lille
- Department Name
- Blood Disorders
- Principal Investigator Name
- Louis TERRIOU
- Principal Investigator Email
- louis.terriou@chru-lille.fr
- Contact Person Name
- Louis TERRIOU
- Contact Person Email
- louis.terriou@chru-lille.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Hematology
- Principal Investigator Name
- Fiorenza BARRACO
- Principal Investigator Email
- fiorenza.barraco@chu-lyon.fr
- Contact Person Name
- Fiorenza BARRACO
- Contact Person Email
- fiorenza.barraco@chu-lyon.fr
Lithuania
- Earliest CTIS Part Ii Submission Date
- 12-06-2024
- Latest Decision Or Authorization Date
- 23-07-2024
- Processing Time Days
- 41
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Vilniaus Universiteto Ligonine Santaros Klinikos Vsi
- Department Name
- Hematology, Oncology and Transfusion Medicine Center
- Principal Investigator Name
- Andrius Degulys
- Principal Investigator Email
- Andrius.Degulys@santa.lt
- Contact Person Name
- Andrius Degulys
- Contact Person Email
- Andrius.Degulys@santa.lt
Netherlands
- Earliest CTIS Part Ii Submission Date
- 12-06-2024
- Latest Decision Or Authorization Date
- 28-06-2024
- Processing Time Days
- 16
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Academic Medical Center at the University of Amsterdam
- Department Name
- Dept Hematology
- Principal Investigator Name
- Erfan Nur
- Principal Investigator Email
- e.nur@amsterdamumc.nl
- Contact Person Name
- Erfan Nur
- Contact Person Email
- e.nur@amsterdamumc.nl
Portugal
- Earliest CTIS Part Ii Submission Date
- 12-06-2024
- Latest Decision Or Authorization Date
- 08-07-2024
- Processing Time Days
- 26
- Number Of Sites
- 3
- Number Of Participants
- 5
Sites
- Site Name
- Instituto Portugues De Oncologia De Lisboa Francisco Gentil E.P.E.
- Department Name
- Serviço Hematologia e Oncologia Médica
- Principal Investigator Name
- Albertina Nunes
- Principal Investigator Email
- alnunes@ipolisboa.min-saude.pt
- Contact Person Name
- Albertina Nunes
- Contact Person Email
- alnunes@ipolisboa.min-saude.pt
- Site Name
- Unidade Local De Saude De Santo Antonio E.P.E.
- Department Name
- Serviço de Hematologia Clínica
- Principal Investigator Name
- Patrícia Seabra
- Principal Investigator Email
- pseabra.hematologiaclinica@chporto.min-saude.pt
- Contact Person Name
- Patrícia Seabra
- Contact Person Email
- pseabra.hematologiaclinica@chporto.min-saude.pt
- Site Name
- Unidade Local De Saude Da Regiao De Aveiro E.P.E.
- Department Name
- Serviço de Hematologia
- Principal Investigator Name
- Fernando Silva
- Principal Investigator Email
- Fernando.Silva.70836@chbv.min-saude.pt
- Contact Person Name
- Fernando Silva
- Contact Person Email
- Fernando.Silva.70836@chbv.min-saude.pt
Romania
- Earliest CTIS Part Ii Submission Date
- 12-06-2024
- Latest Decision Or Authorization Date
- 01-07-2024
- Processing Time Days
- 19
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Spitalul Universitar De Urgenta Bucuresti
- Department Name
- Sectia Hematologie
- Principal Investigator Name
- Ana Maria Vladareanu
- Principal Investigator Email
- anamariavladareanu@yahoo.com
- Contact Person Name
- Ana Maria Vladareanu
- Contact Person Email
- anamariavladareanu@yahoo.com
Poland
- Earliest CTIS Part Ii Submission Date
- 12-06-2024
- Latest Decision Or Authorization Date
- 23-07-2024
- Processing Time Days
- 41
- Number Of Sites
- 3
- Number Of Participants
- 7
Sites
- Site Name
- Mtz Clinical Research Powered By Pratia
- Principal Investigator Name
- Joanna Drozd-Sokołowska
- Principal Investigator Email
- badacz@pratia.com
- Contact Person Name
- Joanna Drozd-Sokołowska
- Contact Person Email
- badacz@pratia.com
- Site Name
- Uniwersytecki Szpital Kliniczny Nr 1 W Lublinie
- Department Name
- Klinika Hematoonkologii i Transplantacji Szpiku
- Principal Investigator Name
- Justyna Kozińska
- Principal Investigator Email
- justynakozinska@vp.pl
- Contact Person Name
- Justyna Kozińska
- Contact Person Email
- justynakozinska@vp.pl
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Klinika Hematologii i Transplantologii
- Principal Investigator Name
- Agnieszka Piekarska
- Principal Investigator Email
- babajaga@gumed.edu.pl
- Contact Person Name
- Agnieszka Piekarska
- Contact Person Email
- babajaga@gumed.edu.pl
Spain
- Earliest CTIS Part Ii Submission Date
- 12-06-2024
- Latest Decision Or Authorization Date
- 01-07-2024
- Processing Time Days
- 19
- Number Of Sites
- 8
- Number Of Participants
- 12
Sites
- Site Name
- El Hospital Universitario De Gran Canaria Dr. Negrin
- Department Name
- Hematology
- Principal Investigator Name
- Silvia Narcisa de la Iglesia Iñigo
- Principal Investigator Email
- siglini@gmail.com
- Contact Person Name
- Silvia Narcisa de la Iglesia Iñigo
- Contact Person Email
- siglini@gmail.com
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Hematology
- Principal Investigator Name
- Monica Ballesteros Andres
- Principal Investigator Email
- monicabandres@hotmail.com
- Contact Person Name
- Monica Ballesteros Andres
- Contact Person Email
- monicabandres@hotmail.com
- Site Name
- Hospital San Pedro De Alcantara
- Department Name
- Hematology
- Principal Investigator Name
- Juan Miguel Bergua Burgues
- Principal Investigator Email
- jmberguaburg@gmail.com
- Contact Person Name
- Juan Miguel Bergua Burgues
- Contact Person Email
- jmberguaburg@gmail.com
- Site Name
- Hospital Clinico San Carlos
- Department Name
- Hematology
- Principal Investigator Name
- Fernando Ataulfo Gonzalez Fernandez
- Principal Investigator Email
- fernandoataulfo.gonzalez@salud.madrid.org
- Contact Person Name
- Fernando Ataulfo Gonzalez Fernandez
- Contact Person Email
- fernandoataulfo.gonzalez@salud.madrid.org
- Site Name
- Hospital Universitario La Paz
- Department Name
- Hematology
- Principal Investigator Name
- Marta Morado Arias
- Principal Investigator Email
- mmorado.hulp@salud.madrid.org
- Contact Person Name
- Marta Morado Arias
- Contact Person Email
- mmorado.hulp@salud.madrid.org
- Site Name
- Hospital Clinic De Barcelona
- Department Name
- Hematology
- Principal Investigator Name
- Anna Gaya Valls
- Principal Investigator Email
- agayav@clinic.cat
- Contact Person Name
- Anna Gaya Valls
- Contact Person Email
- agayav@clinic.cat
- Site Name
- Hospital Germans Trias I Pujol
- Department Name
- Hematology
- Principal Investigator Name
- Ines Hernandez Rodriguez
- Principal Investigator Email
- ihernandez@iconcologia.net
- Contact Person Name
- Ines Hernandez Rodriguez
- Contact Person Email
- ihernandez@iconcologia.net
- Site Name
- Hospital Universitario Basurto
- Department Name
- Hematology
- Principal Investigator Name
- Cristina de Barrenetxea Lekue
- Principal Investigator Email
- cristina.barrene@gmail.com
- Contact Person Name
- Cristina de Barrenetxea Lekue
- Contact Person Email
- cristina.barrene@gmail.com
Germany
- Earliest CTIS Part Ii Submission Date
- 12-06-2024
- Latest Decision Or Authorization Date
- 28-06-2024
- Processing Time Days
- 16
- Number Of Sites
- 2
- Number Of Participants
- 8
Sites
- Site Name
- Universitaetsklinikum Ulm AöR
- Department Name
- Institut für Transfusionsmedizin
- Principal Investigator Name
- Hubert Schrezenmeier
- Principal Investigator Email
- h.schrezenmeier@blutspende.de
- Contact Person Name
- Hubert Schrezenmeier
- Contact Person Email
- h.schrezenmeier@blutspende.de
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- Klinik für Hämatologie und Stammzelltransplantation
- Principal Investigator Name
- Alexander Roeth
- Principal Investigator Email
- alexander.roeth@uk-essen.de
- Contact Person Name
- Alexander Roeth
- Contact Person Email
- alexander.roeth@uk-essen.de
Sponsor
Primary sponsor
- Full Name
- F. Hoffmann-La Roche AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- Parexel International Limited
- Responsibilities
- Randomization
- Name
- Icon Clinical Research Limited
- Responsibilities
- Patient Reported Outcomes
- Name
- IQVIA Limited
- Responsibilities
- FSP monitoring; Global CRO; patient reported outcomes functions (IQVIA Inc. and IQVIA Limited entries provide CRO services)
- Name
- Fortrea Inc.
- Responsibilities
- Mobile Clinical Services
- Name
- Icon Development Solutions LLC
- Responsibilities
- Analytical Laboratory / analytical support
Third parties
- {"country":"Belgium","full_name":"Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi","duties_or_roles":"Patient Reported Outcomes","organisation_type":"Patient organisation/association"}
- {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Mobile Clinical Services","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"FACIT.Org Inc.","duties_or_roles":"Patient Reported Outcomes","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Parexel International Limited","duties_or_roles":"Randomization","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Patient Reported Outcomes","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Iqvia Inc.","duties_or_roles":"Patient Reported Outcomes","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"FSP monitoring","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"Analytical Laboratory","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"Analytical Laboratory","organisation_type":"Pharmaceutical company"}
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Central lab","organisation_type":"Pharmaceutical company"}
- {"country":"Japan","full_name":"Cmic Pharma Science Co. Ltd.","duties_or_roles":"Analytical Laboratory","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Publicis Healthcare Communications Group Limited","duties_or_roles":"Patient and site materials","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Global CRO","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Analytical Laboratory","organisation_type":"Non-Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Crovalimab
- Active Substance
- CROVALIMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS
- Route
- Intravenous
- Authorisation Status
- prodAuthStatus 1
- Maximum Dose
- 1500 mg
- Investigational Product Name
- ECULIZUMAB
- Active Substance
- ECULIZUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INTRAVENOUS
- Route
- Intravenous
- Authorisation Status
- prodAuthStatus 2
- Maximum Dose
- 900 mg
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