Clinical trial • Phase III • Haematology

CROVALIMAB for Paroxysmal nocturnal hemoglobinuria (PNH)

Phase III trial of CROVALIMAB for Paroxysmal nocturnal hemoglobinuria (PNH).

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Paroxysmal nocturnal hemoglobinuria (PNH)
Trial Stage
Phase III
Drug Modality
Monoclonal antibody
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
08-05-2024
First CTIS Authorization Date
11-06-2024

Trial design

Randomised, open-label, eculizumab (eculizumab) - concentrate for solution for infusion; comparator (dosing per approved dosing recommended for pnh; specific dose/schedule not specified in the record)-controlled Phase III trial in Ireland, Sweden, Netherlands and others.

Randomised
Yes
Open Label
Yes
Comparator
Eculizumab (ECULIZUMAB) - CONCENTRATE FOR SOLUTION FOR INFUSION; comparator (dosing per approved dosing recommended for PNH; specific dose/schedule not specified in the record)
Target Sample Size
84
Trial Duration For Participant
175

Eligibility

Recruits 84 paediatric patients.

Pregnancy Exclusion
Pregnant or breastfeeding, or intending to become pregnant during the study or within 46 weeks (approximately 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) Note: In France and Czech republic female patients of childbearing potential are not eligible to participate in the study.
Vulnerable Population
Vulnerable populations include pediatric participants (age ranges include infants/children/adolescents). Consent/assent procedures are specified: parental/legal guardian informed consent required for minors; age‑appropriate assent forms are provided (documents listed for age groups e.g. 7-11 years, 12-15/12-17 years); infant/parental authorization forms are provided for youngest participants. Note: in France and Czech Republic patients under 18 years are not eligible.

Inclusion criteria

  • {"criterion_text":"- General Inclusion Criteria (All Patients) Body weight >= 40 kg at screening (pediatric patients with body weight <40 kg)\n- General Inclusion Criteria (All Patients) Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry evaluation of WBCs\n- General Inclusion Criteria (All Patients) Platelet count >= 30,000/mm3 at screening without transfusion support within 7 days of lab testing\n- For Patients in Randomized Arms (Arm A and B) Age >= 18 years Documented treatment with eculizumab according to the approved dosing recommended for PNH and completion of a minimum of 24 weeks of treatment prior to Day 1\n- For Patients in Randomized Arms (Arm A and B) Lactate dehydrogenase (LDH) <= 1.5 × ULN at screening\n- For Patients in Non-Randomized Arm (Arm C) - Age ≥2 to <18 years with a body weight ≥ 5 kg, currently treated with eculizumab OR - Currently treated with ravulizumab OR - Currently treated with eculizumab at higher-than-approved doses OR - Patients with known C5 polymorphism and poorly controlled hemolysis by eculizumab or ravulizumab - For adult patients currently treated with approved doses of eculizumab Note: In France and Czech Republic patients under 18 years of age are not eligible to participate in the study."}

Exclusion criteria

  • {"criterion_text":"- Major Adverse Vascular Event within 6 months prior to first drug administration (Day 1)\n- History of allogeneic bone marrow transplantation\n- 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- Pregnant or breastfeeding, or intending to become pregnant during the study or within 46 weeks (approximately 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) Note: In France and Czech republic female patients of childbearing potential are not eligible to participate in the study.\n- 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 patient, or would, in the opinion of the Investigator, preclude the patient’s safe participation in and completion of the study"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1. Incidence and severity of adverse events","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 2. Change from baseline in targeted vital signs","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 3. Change from baseline in targeted clinical laboratory test results","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 4. Incidence and severity of injection-site reactions, infusion-related reactions, hypersensitivity, and infections","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 5. Incidence of adverse events leading to study drug discontinuation","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 6. Incidence and severity of clinical manifestations of drug-target-drug complex formation in patients who switched to crovalimab treatment from eculizumab or ravulizumab treatment","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- 1. Serum concentration of crovalimab or eculizumab","definition_or_measurement_approach":"Serum concentration measurement (pharmacokinetic assessments)"}
  • {"endpoint_text":"- 2. Serum concentration of ravulizumab","definition_or_measurement_approach":"Serum concentration measurement (pharmacokinetic assessments)"}
  • {"endpoint_text":"- 3. Prevalence and incidence of anti-drug antibodies (ADAs) to crovalimab","definition_or_measurement_approach":"Detection and quantification of anti-drug antibodies using ADA assays"}
  • {"endpoint_text":"- 4. Change over time in pharmacodynamic biomarkers","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 5. Change over time in free C5 concentration in crovalimab-treated patients","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 6. Observed value and absolute change in parameters reflecting hemolysis","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 7. Percent change from baseline in LDH levels averaged over Weeks 21, 23, and 25 based on central laboratory LDH measurements","definition_or_measurement_approach":"Based on central laboratory LDH measurements averaged across Weeks 21, 23 and 25"}
  • {"endpoint_text":"- 8. Proportion of patients who achieve TA from baseline through Week 25 (after 24 weeks on treatment)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 9. Proportion of patients with BTH from baseline through Week 25","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 10. Proportion of patients with stabilization of hemoglobin from baseline through Week 25","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 11. Proportion of patients with central LDH ≤ 1.5 X ULN from baseline through Week 25","definition_or_measurement_approach":"Central laboratory LDH measurements"}
  • {"endpoint_text":"- 12. Proportion of patients with central LDH ≤ 1 X ULN from baseline through Week 25","definition_or_measurement_approach":"Central laboratory LDH measurements"}
  • {"endpoint_text":"- 13. Total number of units (based on local equivalent) of pRBCs transfused per patient by Week 25","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 14. Proportion of patients who have experienced a MAVE from baseline through Week 25","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 15. Proportion of patients who reach or maintain a hemoglobin level of at least 10 g/dL, without subsequent decrease below 9 g/dL, in the absence of a transfusion","definition_or_measurement_approach":""}
  • {"endpoint_text":"- 16. Mean change from baseline to Week 25 in fatigue, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue] (for adults aged ≥ 18 years)","definition_or_measurement_approach":"Assessed by FACIT-Fatigue questionnaire (adults ≥ 18 years)"}
  • {"endpoint_text":"- 17. Mean change from baseline to Week 25 in Physical Functioning, Role Functioning, and Global Health Status (GHS)/Quality of Life (QoL) scales of the EORTC QLQ-C30, and select disease-related symptoms (abdominal pain, headaches, dyspnea, dysphagia, chest pain, and erectile dysfunction) of the EORTC Item Library (for patients aged ≥ 18 years)","definition_or_measurement_approach":"Assessed by EORTC QLQ-C30 scales and selected EORTC Item Library items (patients ≥ 18 years)"}
  • {"endpoint_text":"- 18. Mean change from baseline to Week 25 in Pediatric Quality of Life Inventory™ (PedsQL™) Multidimensional Fatigue Scale (MFS), and the Physical Functioning scale of the PedsQL Core (for patients aged 8-17 years)","definition_or_measurement_approach":"Assessed by PedsQL Multidimensional Fatigue Scale and PedsQL Core (patients 8-17 years)"}
  • {"endpoint_text":"- 19. Proportion of patients with preference for crovalimab after switching from eculizumab or ravulizumab at Week 17 (Arms A and C), as assessed through use of a Patient Preference Questionnaire developed by the Sponsor (for patients aged ≥ 12 years)","definition_or_measurement_approach":"Assessed using a sponsor-developed Patient Preference Questionnaire (patients ≥ 12 years)"}
  • {"endpoint_text":"- 20. Mean treatment satisfaction with crovalimab or eculizumab at Week 25, as assessed by the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) (for patients aged ≥ 18 years)","definition_or_measurement_approach":"Assessed by TSQM-9 (patients ≥ 18 years)"}

Recruitment

Planned Sample Size
84
Recruitment Window Months
113
Consent Approach
Informed consent is obtained from adult participants; for minors parental/legal guardian informed consent is required. Age-appropriate assent forms are provided (documents for age groups such as 7-11 years, 12-15/12-17 years are included). Infant authorization / parental ICF documents are present for the youngest participants. Consent and ICF materials are available in multiple country/language versions per participating Member State (multiple language-specific ICFs and assent/parental forms listed in the trial documents). Note: in France and Czech Republic patients under 18 years are not eligible.

Geography

Total Number Of Sites
32
Total Number Of Participants
77

Ireland

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
09-09-2025
Processing Time Days
473
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
St James's Hospital
Department Name
Haematology
Contact Person Name
Catherine Flynn
Contact Person Email
cmflynn@stjames.ie

Sweden

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
10-09-2025
Processing Time Days
474
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Uppsala University Hospital
Department Name
Dept. of Hematology
Contact Person Name
Martin Hoglund
Contact Person Email
martin.hoglund@medsci.uu.se

Netherlands

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
27-11-2024
Processing Time Days
187
Number Of Sites
1
Number Of Participants
6

Sites

Site Name
Amsterdam UMC Stichting
Department Name
Department of Hematology
Contact Person Name
Erfan Nur
Contact Person Email
e.nur@amsterdamumc.nl

Germany

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
02-12-2024
Processing Time Days
192
Number Of Sites
2
Number Of Participants
5

Sites

Site Name
ELBLANDKLINIKEN Stiftung & Co. KG
Department Name
Klinik fuer Innere Medizin III
Contact Person Name
Joerg Schubert
Site Name
Universitaetsklinikum Aachen AöR
Department Name
Medizinische Klinik IV
Contact Person Name
Jens Panse
Contact Person Email
jpanse@ukaachen.de

Czechia

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
27-11-2024
Processing Time Days
187
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Institute Of Hematology And Blood Transfusion
Department Name
Hematology
Contact Person Name
Jaroslav Čermák
Contact Person Email
jaroslav.cermak@uhkt.cz

Estonia

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
12-09-2025
Processing Time Days
476
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
North Estonia Medical Centre Foundation
Department Name
Hematology
Contact Person Name
Iige Viigimaa

France

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
12-09-2025
Processing Time Days
476
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Hematology
Contact Person Name
Louis TERRIOU
Contact Person Email
louis.terriou@chru-lille.fr
Site Name
Institut Paoli Calmettes
Department Name
Hematology
Contact Person Name
Yosr HICHERI
Contact Person Email
HICHERIY@ipc.unicancer.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Hematology
Contact Person Name
Sophie DE GUIBERT

Italy

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
10-09-2025
Processing Time Days
474
Number Of Sites
4
Number Of Participants
10

Sites

Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
Hematology
Contact Person Name
Francesco Lanza
Contact Person Email
francesco.lanza@auslromagna.it
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
Hematology
Contact Person Name
Valentina Giai
Contact Person Email
vgiai@cittadellasalute.to.it
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
Hematology
Contact Person Name
Bruno Fattizzo
Site Name
Careggi University Hospital
Department Name
Hematology
Contact Person Name
Barbara Scappini

Portugal

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
14-05-2025
Processing Time Days
355
Number Of Sites
2
Number Of Participants
8

Sites

Site Name
Unidade Local De Saude Da Regiao De Aveiro E.P.E.
Department Name
Serviço de Hematologia
Contact Person Name
Fernando Silva
Site Name
Unidade Local De Saude De Santo Antonio E.P.E.
Department Name
Serviço de Hematologia Clínica
Contact Person Name
Patrícia Seabra

Belgium

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
11-09-2025
Processing Time Days
475
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
Algemeen Ziekenhuis Delta
Department Name
Hematology
Contact Person Name
Dries Deeren
Contact Person Email
dries.deeren@azdelta.be
Site Name
Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur
Department Name
Hematology
Contact Person Name
Berangere Devalet
Site Name
Cliniques Universitaires Saint-Luc
Department Name
Hematology
Contact Person Name
Xavier Poiré

Spain

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
11-09-2025
Processing Time Days
475
Number Of Sites
10
Number Of Participants
17

Sites

Site Name
Hospital Clinico San Carlos
Department Name
Hematology
Contact Person Name
Fernando Ataulfo Gonzalez Fernandez
Site Name
El Hospital Universitario De Gran Canaria Dr. Negrin
Department Name
Hematology
Contact Person Name
Silvia Narcisa de la Iglesia Iñigo
Contact Person Email
siglini@gmail.com
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Hematology
Contact Person Name
Ramiro Nuñez Vazquez
Contact Person Email
ramirojosenv@gmail.com
Site Name
Hospital Universitario De Salamanca
Department Name
Hematology
Contact Person Name
Maria Belen Vidriales Vicente
Site Name
Hospital Universitario De Toledo
Department Name
Hematology
Contact Person Name
Jorge Cuesta Tovar
Contact Person Email
jorgecuestatovar@gmail.com
Site Name
Hospital Unviersitario Miguel Servet
Department Name
Hematology
Contact Person Name
Maria del Valle Recasens Flores
Contact Person Email
vrecasens@salud.aragon.es
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Hematology
Contact Person Name
Mónica Ballesteros Andres
Contact Person Email
monicabandres@hotmail.com
Site Name
Hospital Universitario Regional De Malaga
Department Name
Hematology
Contact Person Name
Alejandro Contento Gonzalo
Site Name
Hospital Universitario Basurto
Department Name
Hematology
Contact Person Name
Cristina de Barrenetxea Lekue
Contact Person Email
cristina.barrene@gmail.com
Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Hematology
Contact Person Name
Ana Maria Fernandez Villar
Contact Person Email
ana.fernandez.villar@gmail.com

Poland

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
12-09-2025
Processing Time Days
476
Number Of Sites
4
Number Of Participants
11

Sites

Site Name
Szpital Uniwersytecki Nr 2 Im Dr Jana Biziela W Bydgoszczy
Department Name
Klinika Hematologii
Contact Person Name
Marta Sobas
Contact Person Email
marta.sobas@gmail.com
Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Klinika Hematologii i Transplantologii
Contact Person Name
Agnieszka Piekarska
Contact Person Email
babajaga@gumed.edu.pl
Site Name
Mtz Clinical Research Powered By Pratia
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
Contact Person Name
Justyna Kozińska
Contact Person Email
justynakozinska@vp.pl

Greece

Earliest CTIS Part Ii Submission Date
24-05-2024
Latest Decision Or Authorization Date
26-09-2025
Processing Time Days
490
Number Of Sites
3
Number Of Participants
4

Sites

Site Name
Laiko General Hospital Of Athens
Department Name
Hematology Clinic and Bone Marrow Τransplantation Unit
Contact Person Name
Panayiotis Panayiotidis
Contact Person Email
ppanayi@med.uoa.gr
Site Name
University General Hospital Attikon
Department Name
B Department of Propaedeutic Internal Medicine Clinic
Contact Person Name
Vassiliki Pappa
Contact Person Email
vas_pappa@yahoo.com
Site Name
Geniko Nosokomeio Thessalonikis George Papanikolaou
Department Name
Hematology Clinic
Contact Person Name
Chrysavgi – Elissavet Lalagianni
Contact Person Email
luizana6@gmail.com

Sponsor

Primary sponsor

Full Name
F. Hoffmann-La Roche AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
IQVIA Limited
Responsibilities
Global CRO; FSP monitoring
Name
Parexel International Limited
Responsibilities
Randomization
Name
Icon Clinical Research Limited
Responsibilities
Patient Reported Outcomes
Name
Iqvia Inc.
Responsibilities
Patient Reported Outcomes
Name
Fortrea Inc.
Responsibilities
Mobile Clinical Services

Third parties

  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"FSP monitoring","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Parexel International Limited","duties_or_roles":"Randomization","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"FACIT.Org Inc.","duties_or_roles":"Patient Reported Outcomes","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":"Iqvia Inc.","duties_or_roles":"Patient Reported Outcomes","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":"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"}
  • {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Mobile Clinical Services","organisation_type":"Pharmaceutical company"}
  • {"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":"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":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Patient Reported Outcomes","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"}

Investigational products

Investigational Product Name
Crovalimab
Active Substance
CROVALIMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous
Route
Intravenous
Maximum Dose
1500 mg
Investigational Product Name
Eculizumab
Active Substance
ECULIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous
Route
Intravenous
Maximum Dose
900 mg

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