Clinical trial • Phase III • Haematology

CROVALIMAB for Atypical hemolytic uremic syndrome

Phase III trial of CROVALIMAB for Atypical hemolytic uremic syndrome. open-label. 62 participants.

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Atypical hemolytic uremic syndrome
Trial Stage
Phase III
Drug Modality
Monoclonal antibody
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
25-01-2024
First CTIS Authorization Date
29-02-2024

Trial design

open-label Phase III trial in Italy, Germany, Hungary and others.

Open Label
Yes
Biomarker Stratified
True, biomarker: C5 polymorphism (e.g., Arg885) - C5SNP cohort
Target Sample Size
62

Eligibility

Recruits 62 paediatric patients.

Vulnerable Population
Vulnerable populations selected. Study includes adolescents and infants (documents include ICFs and assent/authorization forms for ages 12-17, adolescent addenda, infant authorization and parent consent forms). Consent is obtained from adult participants; parental consent is documented for minors/infants and assent forms are provided for adolescents (e.g., assent forms for ages 12-17). Multiple country-specific subject information and informed consent forms and assent/parent documents are available (multiple language versions listed in the trial documents).

Inclusion criteria

  • {"criterion_text":"- Vaccination against Neisseria meningitidis < 3 years prior to initiation of study treatment in accordance with current local guidelines or standard of care, as applicable in patients with complement deficiency (for ALL cohorts)\n- Adequate hepatic function, AST and ALT ≤ 3×ULN at the time of screening; no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis (for ALL cohorts)\n- For female patients of childbearing potential, an agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception (for ALL cohorts)\n- Onset of initial TMA presentation, within 28 days prior to the first dose of crovalimab (For naïve cohort only)\n- Clinical evidence of response to either eculizumab or ravulizumab, as documented by a platelet count ≥LLN, LDH ≤ULN, and stable (decrease or increase of ≤20%) or improving creatinine at two consecutive measurements at least 4 weeks apart prior to Week 1 Day 1 of crovalimab treatment. (For switch cohort only)\n- Known C5 polymorphism (e.g., Arg885) (For C5SNP cohort only)"}

Exclusion criteria

  • {"criterion_text":"- TMA associated with non-aHUS-related renal disease\n- History of a kidney disease other than aHUS, affecting renal function\n- Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome\n- Active systemic bacterial, viral, or fungal infection within 14 days before first crovalimab administration\n- History of Neisseria meningitidis infection within 6 months of study enrollment\n- History of malignancy within 5 years prior to screening and up to the first crovalimab administration"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1. Proportion of patients with complete TMA response (cTMAr)","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- 1. Dialysis requirement status (yes/no) change\n- 2. Observed value and change from baseline in estimated glomerular filtration rate (eGFR)\n- 3. Proportion of patients with change from baseline in chronic kidney disease stage\n- 4. Observed value and change from baseline in hematologic parameters\n- 5. In adults (≥ 18 years), change from baseline in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Questionnaire\n- 6. Incidence and severity of adverse events\n- 7. Change in targeted vital signs and clinical laboratory test results\n- 8. Incidence and severity of injection-site reactions, infusion-related reactions, hypersensitivity, malignant hypertension, and infections\n- 9. Incidence of adverse events leading to study drug discontinuation\n- 10. Serum concentrations of crovalimab\n- 11. Prevalence and incidence of anti-drug antibodies (ADAs) to crovalimab\n- 12. Proportion of patients with platelet count ≥ LLN\n- 13. Proportion of patients with normalization of LDH\n- 14. Proportion of patients with ≥ 25% decrease in serum creatinine from baseline\n- 15. Time to cTMAr\n- 16. Duration of cTMAr\n- 17. Proportion of patients with cTMAr\n- 18. Proportion of patients with maintained TMA control (mTMAc)","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
62
Recruitment Window Months
97
Consent Approach
Informed consent materials and procedures documented. Adult main ICFs are provided for adult participants; parental consent forms and infant authorization forms are provided for infants; assent forms and adolescent addenda (e.g., ages 12-17) are provided for minors. Multiple language versions and country-specific ICFs and assent forms are included in the submitted documents (examples include EN, FR, DE, NL, HU, ES, PL versions listed among the trial documents).

Geography

Total Number Of Sites
23
Total Number Of Participants
19

Italy

Earliest CTIS Part Ii Submission Date
13-02-2024
Latest Decision Or Authorization Date
27-11-2024
Processing Time Days
288
Number Of Sites
4
Number Of Participants
3

Sites

Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
Clinica Nefrologica Dialisi e Trapianto
Principal Investigator Name
Francesca Chiara Viazzi
Principal Investigator Email
francesca.viazzi@unige.it
Contact Person Name
Francesca Chiara Viazzi
Contact Person Email
francesca.viazzi@unige.it
Site Name
Careggi University Hospital
Department Name
Nefrologia
Principal Investigator Name
Calogero Lino Cirami
Principal Investigator Email
ciramil@aou-careggi.toscana.it
Contact Person Name
Calogero Lino Cirami
Contact Person Email
ciramil@aou-careggi.toscana.it
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
Nefrologia, Dialisi e Trapianto Renale
Principal Investigator Name
Anna Regalia
Principal Investigator Email
anna.regalia@policlinico.mi.it
Contact Person Name
Anna Regalia
Contact Person Email
anna.regalia@policlinico.mi.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
UOC Nefrologia
Principal Investigator Name
Giuseppe Grandaliano
Principal Investigator Email
giuseppe.grandaliano@policlinicogemelli.it
Contact Person Name
Giuseppe Grandaliano

Germany

Earliest CTIS Part Ii Submission Date
13-02-2024
Latest Decision Or Authorization Date
02-12-2024
Processing Time Days
293
Number Of Sites
4
Number Of Participants
6

Sites

Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Nephrologie, Klinik für Infektiologie, Medizinisches Forschungszentrum (MFZ)
Principal Investigator Name
Anja Gäckler
Principal Investigator Email
anja.gaeckler@uk-essen.de
Contact Person Name
Anja Gäckler
Contact Person Email
anja.gaeckler@uk-essen.de
Site Name
University Hospital Cologne AöR
Department Name
Klinik II für Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin
Principal Investigator Name
Paul Brinkkötter
Principal Investigator Email
paul.brinkkoetter@uk-koeln.de
Contact Person Name
Paul Brinkkötter
Contact Person Email
paul.brinkkoetter@uk-koeln.de
Site Name
Medizinische Hochschule Hannover
Department Name
Klinik für Nieren- und Hochdruckerkrankungen
Principal Investigator Name
Kai Schmidt-Ott
Principal Investigator Email
studienzentrum@mh-hannover.de
Contact Person Name
Kai Schmidt-Ott
Contact Person Email
studienzentrum@mh-hannover.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Kinder- und Jugendmedizin, Pädiatrie II
Principal Investigator Name
Anja Büscher
Principal Investigator Email
anja.buescher@uk-essen.de
Contact Person Name
Anja Büscher
Contact Person Email
anja.buescher@uk-essen.de

Hungary

Earliest CTIS Part Ii Submission Date
13-02-2024
Latest Decision Or Authorization Date
25-11-2024
Processing Time Days
286
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Del-Pesti Centrumkorhaz Orszagos Hematologiai Es Infektologiai Intezet
Department Name
Hematologia
Principal Investigator Name
Marienn Reti
Principal Investigator Email
reti.marienn@dpckorhaz.hu
Contact Person Name
Marienn Reti
Contact Person Email
reti.marienn@dpckorhaz.hu

Spain

Earliest CTIS Part Ii Submission Date
13-02-2024
Latest Decision Or Authorization Date
29-11-2024
Processing Time Days
290
Number Of Sites
4
Number Of Participants
2

Sites

Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Nephrology
Principal Investigator Name
Mercedes Cao Vilariño
Principal Investigator Email
mercedes.cao.vilarino@sergas.es
Contact Person Name
Mercedes Cao Vilariño
Site Name
Hospital Universitario 12 De Octubre
Department Name
Nephrology
Principal Investigator Name
Francisco De la Cerda Ojeda
Principal Investigator Email
nefroped.hvr.sspa@juntadeandalucia.es
Contact Person Name
Francisco De la Cerda Ojeda
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Nephrology
Principal Investigator Name
Jose Luis Rocha Castilla
Principal Investigator Email
josel.rocha.sspa@juntadeandalucia.es
Contact Person Name
Jose Luis Rocha Castilla
Site Name
Hospital Clinic De Barcelona
Department Name
Nephrology
Principal Investigator Name
Luis Quintana Pollas
Principal Investigator Email
lfquinta@clinic.cat
Contact Person Name
Luis Quintana Pollas
Contact Person Email
lfquinta@clinic.cat

France

Earliest CTIS Part Ii Submission Date
13-02-2024
Latest Decision Or Authorization Date
25-11-2024
Processing Time Days
286
Number Of Sites
5
Number Of Participants
3

Sites

Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Hôpital LAPEYRONIE - néphrologie
Principal Investigator Name
Moglie LE QUINTREC
Principal Investigator Email
m-lequintrec-donnette@chu-montpellier.fr
Contact Person Name
Moglie LE QUINTREC
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Hôpital Arnaud de Villeneuve - néphrologie
Principal Investigator Name
Marc FILA
Principal Investigator Email
m-fila@chu-montpellier.fr
Contact Person Name
Marc FILA
Contact Person Email
m-fila@chu-montpellier.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
TENON - Service SINRA
Principal Investigator Name
Laurent MESNARD
Principal Investigator Email
laurent.mesnard@aphp.fr
Contact Person Name
Laurent MESNARD
Contact Person Email
laurent.mesnard@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
GH NECKER - enfants malades - néphrologie
Principal Investigator Name
Olivia BOYER
Principal Investigator Email
olivia.boyer@aphp.fr
Contact Person Name
Olivia BOYER
Contact Person Email
olivia.boyer@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
CHU ROBERT DEBRE - néphrologie pédiatrique
Principal Investigator Name
Julien HOGAN
Principal Investigator Email
julien.hogan2@aphp.fr
Contact Person Name
Julien HOGAN
Contact Person Email
julien.hogan2@aphp.fr

Belgium

Earliest CTIS Part Ii Submission Date
13-02-2024
Latest Decision Or Authorization Date
02-12-2024
Processing Time Days
293
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
UZ Leuven
Department Name
Nephrology
Principal Investigator Name
Kathleen Claes
Principal Investigator Email
kathleen.claes@uzleuven.be
Contact Person Name
Kathleen Claes
Contact Person Email
kathleen.claes@uzleuven.be

Poland

Earliest CTIS Part Ii Submission Date
13-02-2024
Latest Decision Or Authorization Date
02-12-2024
Processing Time Days
293
Number Of Sites
4
Number Of Participants
2

Sites

Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Klinika Chorób Nerek i Nadciśnienia Dzieci i Młodzieży
Principal Investigator Name
Aleksandra Żurowska
Principal Investigator Email
nefped@gumed.edu.pl
Contact Person Name
Aleksandra Żurowska
Contact Person Email
nefped@gumed.edu.pl
Site Name
Instytut Centrum Zdrowia Matki Polki
Department Name
Klinika Pediatrii i Immunologii i Nefrologii
Principal Investigator Name
Marcin Tkaczyk
Principal Investigator Email
sek31@iczmp.edu.pl
Contact Person Name
Marcin Tkaczyk
Contact Person Email
sek31@iczmp.edu.pl
Site Name
Samodzielny Publiczny Szpital Kliniczny Nr 1 Im.Prof.Stanislawa Szyszko Slaskiego Uniwersytetu Medycznego W Katowicach
Department Name
Oddział Nefrologii Dzieci z Pododdziałem Dializoterapii
Principal Investigator Name
Maria Szczepańska
Principal Investigator Email
mszczepanska@szpital.zabrze.pl
Contact Person Name
Maria Szczepańska
Contact Person Email
mszczepanska@szpital.zabrze.pl
Site Name
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
Department Name
Klinika Nefrologii, Dializoterapii i Chorób Wewnętrznych
Principal Investigator Name
Jolanta Małyszko
Principal Investigator Email
nefrologia@wum.edu.pl
Contact Person Name
Jolanta Małyszko
Contact Person Email
nefrologia@wum.edu.pl

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

Third parties

  • {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"Other third party duty","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Japan","full_name":"Cmic Pharma Science Co. Ltd.","duties_or_roles":"Specialty Laboratory","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"3","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp","duties_or_roles":"Specialty Laboratory","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Fulgent Genetics Inc.","duties_or_roles":"Specialty Laboratory","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Global CRO","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"Specialty Laboratory","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Teckro Limited","duties_or_roles":"Medical Communication","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Specialty Laboratory","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Specialty Laboratory","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Specialty Laboratory","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Spain","full_name":"Secugen S.L.","duties_or_roles":"Specialty Laboratory","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"SampleManagementWhitesboro@iconplc.com","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Crovalimab
Active Substance
CROVALIMAB
Modality
Monoclonal antibody
Routes Of Administration
Subcutaneous; Intravenous
Route
Subcutaneous and Intravenous
Maximum Dose
1500 mg per day

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