Overview
Sponsor-declared trial summary
Phase
Human pharmacology (Phase I) - Other
Status
Ended
Participants planned
53
Countries
4
Sites
7
Sickle Cell Disease
To evaluate the safety of crovalimab compared with placebo
Key facts
- Sponsor
- F. Hoffmann-La Roche AG
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Trial duration
- 11 Sep 2023 → 15 Aug 2025
- Decision date (initial)
- 2023-07-25
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- F. Hoffmann-La Roche AG
External identifiers
- EU CT number
- 2022-502546-26-00
- EudraCT number
- 2020-004840-27
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Safety, Pharmacokinetic, Efficacy
To evaluate the safety of crovalimab compared with placebo
Secondary objectives 4
- To evaluate the pharmacokinetics (PK) of crovalimab
- To evaluate the pharmacodynamics (PD) of crovalimab
- To evaluate the efficacy of crovalimab compared with placebo
- To evaluate the immune response to crovalimab
Conditions and MedDRA coding
Sickle Cell Disease
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10072397 | Vaso-occlusive crisis | 10005329 |
| 21.0 | PT | 10040644 | Sickle cell disease | 100000004850 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Treatment Patients will be randomized 2:1 to receive either a single intravenous (IV) tiered weight-based dose of crovalimab or placebo.
|
Randomised Controlled | Double | [{"id":134322,"code":5,"name":"Carer"},{"id":134318,"code":4,"name":"Analyst"},{"id":134320,"code":2,"name":"Investigator"},{"id":134321,"code":3,"name":"Monitor"},{"id":134319,"code":1,"name":"Subject"}] | Crovalimab + SOC for VOE: Single dose of crovalimab Placebo + SOC for VOE: Single dose of placebo |
| 2 | Follow up (blinded) Patients will be followed for the duration of the hospitalization until the time of discharge. After discharge, they will continue to be followed during an observational period on Days 14, 28, 46, 64, and 84 after study treatment administration
|
Not Applicable | Double | [{"id":134325,"code":2,"name":"Investigator"},{"id":134326,"code":3,"name":"Monitor"},{"id":134327,"code":4,"name":"Analyst"},{"id":134328,"code":5,"name":"Carer"},{"id":134324,"code":1,"name":"Subject"}] | |
| 3 | Safety follow up For safety follow-up, two telephone calls will be conducted on Day 168 and Day 322. At sites in France, for safety follow-up, one telephone call will be conducted on Day 168 and a study site visit will be conducted on Day 322.
|
Not Applicable | None |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2020-004839-25 | A RANDOMIZED DOUBLE-BLIND PHASE IIA STUDY EVALUATING THE EFFICACY, SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF CROVALIMAB AS ADJUNCT TREATMENT IN PREVENTION OF VASO-OCCLUSIVE EPISODES (VOE) IN SICKLE CELL DISEASE (SCD), STUDIO DI FASE IIA, RANDOMIZZATO E IN DOPPIO CIECO VOLTO A VALUTARE L’EFFICACIA, LA SICUREZZA, LA FARMACOCINETICA E LA FARMACODINAMICA DI CROVALIMAB COME TRATTAMENTO AGGIUNTIVO NELLA PREVENZIONE DI EPISODI VASO-OCCLUSIVI (VOE) NELL’ANEMIA FALCIFORME (SCD), ESTUDIO DE FASE IIA ALEATORIZADO Y DOBLE CIEGO PARA EVALUAR LA EFICACIA, LA SEGURIDAD, LA FARMACOCINÉTICA Y LA FARMACODINÁMICA DE CROVALIMAB COMO TRATAMIENTO COMPLEMENTARIO EN LA PREVENCIÓN DE EPISODIOS VASOOCLUSIVOS (EVO) EN LA ANEMIA DE CÉLULAS FALCIFORMES (ACF) |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Body weight >=40 kg
- Confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia)
- Vaccination against Neisseria Meningitidis,, and vaccinations against H. influenzae type B and S. pneumoniae
- Diagnosis of an acute uncomplicated VOE that requires admission to a hospital/acute medical facility and treatment with parenteral opioid analgesics
- Adequate hepatic and renal function
- Participants receiving sickle cell therapies must be on a stable dose for >=28 days
Exclusion criteria 6
- More than 10 VOEs within the last 12 months prior to presentation that have required a medical facility visit
- Pain related to the current VOE ongoing for >48 hours
- Acute pain related to avascular necrosis, hepatic or splenic sequestration, or priapism, and pain atypical of an acute uncomplicated VOE
- Transfusion or receipt of blood products within 3 months or current participation in a chronic transfusion protocol
- Known or suspected hereditary complement deficiency
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 322 days (approximately 10.5 months) after the study drug administration
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 3
- Incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)
- Change from baseline in targeted vital signs and clinical laboratory test results
- Incidence and severity of infusion-related reactions and hypersensitivity
Secondary endpoints 5
- Serum concentrations of crovalimab over time
- Relationships between drug exposure and pharmacodynamics, efficacy, or safety endpoints of crovalimab (patients randomized to crovalimab)
- Change over time in PD biomarkers (CH50, free C5, sC5b-9)
- Time to improvement of the primary acute uncomplicated VOE from baseline
- Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD9871077 · Product
- Active substance
- Crovalimab
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS (IV) OR SUBCUTANEOUS (SC)
- Authorisation status
- Not Authorised
- MA holder
- F. HOFFMANN-LA ROCHE LTD
- Paediatric formulation
- No
- Orphan designation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
F. Hoffmann-La Roche AG
- Sponsor organisation
- F. Hoffmann-La Roche AG
- Address
- Grenzacherstrasse 124
- City
- Basel
- Postcode
- 4058
- Country
- Switzerland
Scientific contact point
- Organisation
- F. Hoffmann-La Roche AG
- Contact name
- Trial Information System - TISL
Public contact point
- Organisation
- F. Hoffmann-La Roche AG
- Contact name
- Trial Information System - TISL
Third parties 7
| Organisation | City, country | Duties |
|---|---|---|
| Q Squared Solutions Limited ORG-100042527
|
Reading, United Kingdom | Laboratory analysis |
| Labcorp Early Development Laboratories Inc. ORG-100012865
|
Greenfield, United States | Laboratory analysis |
| Teckro Limited ORG-100041454
|
Limerick, Ireland | Other |
| Icon Development Solutions LLC ORG-100012400
|
Whitesboro, United States | Laboratory analysis |
| IQVIA Limited ORG-100008655
|
Reading, United Kingdom | Other |
| Labcorp Central Laboratory Services LP ORG-100032236
|
Indianapolis, United States | Laboratory analysis |
| Perceptive Informatics Inc. ORG-100013171
|
Billerica, United States | Interactive response technologies (IRT) |
Locations
4 EU/EEA countries · 7 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ended | 4 | 2 |
| Italy | Ended | 2 | 1 |
| Netherlands | Ended | 3 | 1 |
| Spain | Ended | 7 | 3 |
| Rest of world
Panama, United Kingdom, United States, Lebanon, South Africa, Canada, Kenya, Brazil
|
— | 37 | — |
Investigational sites
Assistance Publique Hopitaux De Paris
Service de médecine interne, 51 Av Du Mal De Lattre De Tassigny, 94000, Creteil
Centre Hospitalier Universitaire De Montpellier
Service de médecine interne, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5
Centro Ricerche Cliniche Di Verona S.r.l.
U.O.C Medicina Interna B, Piazzale Ludovico Antonio Scuro 10, 37134, Verona
Amsterdam UMC
Hematology, De Boelelaan 1117, 1081 HV, Amsterdam
University Hospital Virgen Del Rocio S.L.
Hematology, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital General Universitario Gregorio Maranon
Hematology, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Unviersitario Miguel Servet
Hematology, Paseo De Isabel La Catolica 1-3, 50009, Zaragoza
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2022-03-09 | 2025-05-26 | 2022-11-15 | 2024-09-30 | |
| Italy | 2021-10-15 | 2025-04-01 | 2022-03-23 | 2024-09-30 | |
| Netherlands | 2023-09-12 | 2025-05-26 | 2024-03-11 | 2024-09-30 | |
| Spain | 2021-07-09 | 2025-03-31 | 2021-09-27 | 2024-09-30 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 6 · Art. 38 CTR
Temporary halt TH-4422
- Halt date
- 2023-08-28
- Planned restart
- 2023-09-06
- Member states concerned
- France
- Publication date
- 2023-09-01
- Reason
- Medicinal Product related
- Explanation
- An interruption of IMP (solution for infusion (IV) from a single-use vial which contains an extractable volume of 2 mL or 340 mg (nominal) crovalimab or placebo supply to clinical sites in the EU was identified due to mold being discovered on the outer (tertiary) packaging of several boxes within the EU IMP Distribution Center. While the root cause for this issue is being assessed, all shipments into and out of the distribution center have been temporarily stopped. The quality of the IMP itself within the primary/secondary packaging is assessed to be uncompromised. There are no safety concerns of the material previously shipped or to be shipped to the sites, respectively.
- Follow-up measures
- An urgent shipment of IMP has been raised from a backup depot and all sites will be resupplied with IMP (by 6 September 2023 the latest).
No potential new patients will be enrolled during this time.
Patients enrolled in study BO42452 are receiving a single IV dose of crovalimab or placebo. Hence, all patients that have been enrolled did already receive their dosing as foreseen in the study protocol. There will be no dose interruptions and patient safety is not affected. - Benefit-risk balance changed
- No
- Treatment stopped
- No
Temporary halt TH-4405
- Halt date
- 2023-08-28
- Planned restart
- 2023-09-06
- Member states concerned
- Spain
- Publication date
- 2024-04-16
- Reason
- Medicinal Product related
- Explanation
- An interruption of IMP (solution for infusion (IV) from a single-use vial which contains an extractable volume of 2 mL or 340 mg (nominal) crovalimab or placebo) supply to clinical sites in the EU was identified due to mold being discovered on the outer (tertiary) packaging of several boxes within the EU IMP Distribution Center. While the root cause for this issue is being assessed, all shipments into and out of the distribution center have been temporarily stopped. The quality of the IMP itself within the primary/secondary packaging is assessed to be uncompromised. There are no safety concerns of the material previously shipped or to be shipped to the sites, respectively.
- Follow-up measures
- No potential new patients will be enrolled during this time.
Patients enrolled in study BO42452 are receiving a single IV dose of crovalimab or placebo. Hence, all patients that have been enrolled did already receive their dosing as foreseen in the study protocol. There will be no dose interruptions and patient safety is not affected. - Benefit-risk balance changed
- No
- Treatment stopped
- No
Temporary halt TH-4406
- Halt date
- 2023-08-28
- Planned restart
- 2023-09-06
- Member states concerned
- Italy
- Publication date
- 2024-04-16
- Reason
- Medicinal Product related
- Explanation
- An interruption of IMP (solution for infusion (IV) from a single-use vial which contains an extractable volume of 2 mL or 340 mg (nominal) crovalimab or placebo) supply to clinical sites in the EU was identified due to mold being discovered on the outer (tertiary) packaging of several boxes within the EU IMP Distribution Center. While the root cause for this issue is being assessed, all shipments into and out of the distribution center have been temporarily stopped. The quality of the IMP itself within the primary/secondary packaging is assessed to be uncompromised. There are no safety concerns of the material previously shipped or to be shipped to the sites, respectively.
- Follow-up measures
- No potential new patients will be enrolled during this time.
Patients enrolled in study BO42452 are receiving a single IV dose of crovalimab or placebo. Hence, all patients that have been enrolled did already receive their dosing as foreseen in the study protocol. There will be no dose interruptions and patient safety is not affected. - Benefit-risk balance changed
- No
- Treatment stopped
- No
Temporary halt TH-21528
- Halt date
- 2023-08-28
- Member states concerned
- France
- Publication date
- 2024-04-16
- Reason
- Medicinal Product related
- Benefit-risk balance changed
- No
- Treatment stopped
- No
Temporary halt TH-4419
- Halt date
- 2023-08-28
- Planned restart
- 2023-09-06
- Member states concerned
- Spain
- Publication date
- 2023-09-01
- Reason
- Medicinal Product related
- Explanation
- An interruption of IMP (solution for infusion (IV) from a single-use vial which contains an extractable volume of 2 mL or 340 mg (nominal) crovalimab or placebo supply to clinical sites in the EU was identified due to mold being discovered on the outer (tertiary) packaging of several boxes within the EU IMP Distribution Center. While the root cause for this issue is being assessed, all shipments into and out of the distribution center have been temporarily stopped. The quality of the IMP itself within the primary/secondary packaging is assessed to be uncompromised. There are no safety concerns of the material previously shipped or to be shipped to the sites, respectively.
- Follow-up measures
- An urgent shipment of IMP has been raised from a backup depot and all sites will be resupplied with IMP (by 6 September 2023 the latest).
No potential new patients will be enrolled during this time.
Patients enrolled in study BO42452 are receiving a single IV dose of crovalimab or placebo. Hence, all patients that have been enrolled did already receive their dosing as foreseen in the study protocol. There will be no dose interruptions and patient safety is not affected. - Benefit-risk balance changed
- No
- Treatment stopped
- No
Temporary halt TH-4420
- Halt date
- 2023-08-28
- Planned restart
- 2023-09-06
- Member states concerned
- Italy
- Publication date
- 2023-09-01
- Reason
- Medicinal Product related
- Explanation
- An interruption of IMP (solution for infusion (IV) from a single-use vial which contains an extractable volume of 2 mL or 340 mg (nominal) crovalimab or placebo supply to clinical sites in the EU was identified due to mold being discovered on the outer (tertiary) packaging of several boxes within the EU IMP Distribution Center. While the root cause for this issue is being assessed, all shipments into and out of the distribution center have been temporarily stopped. The quality of the IMP itself within the primary/secondary packaging is assessed to be uncompromised. There are no safety concerns of the material previously shipped or to be shipped to the sites, respectively.
- Follow-up measures
- An urgent shipment of IMP has been raised from a backup depot and all sites will be resupplied with IMP (by 6 September 2023 the latest).
No potential new patients will be enrolled during this time.
Patients enrolled in study BO42452 are receiving a single IV dose of crovalimab or placebo. Hence, all patients that have been enrolled did already receive their dosing as foreseen in the study protocol. There will be no dose interruptions and patient safety is not affected. - Benefit-risk balance changed
- No
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| BO42452_CTIS Results Summary SUM-118545
|
2026-02-10T09:28:49 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| BO42452_Lay Person Summary reports | 2026-02-26T14:25:10 | Submitted | Laypersons Summary of Results |
Documents 17 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | Final-v2_BO42452-CROSSWALK-a_Final Analysis LPS_19Jan2026 | NA |
| Laypersons summary of results (for publication) | Final-v2_BO42452-CROSSWALK-a_Final-Analysis-LPS_19Jan2026_ES-ES | NA |
| Laypersons summary of results (for publication) | Final-v2_BO42452-CROSSWALK-a_Final-Analysis-LPS_19Jan2026_FR-FR | NA |
| Laypersons summary of results (for publication) | Final-v2_BO42452-CROSSWALK-a_Final-Analysis-LPS_19Jan2026_IT-IT | NA |
| Laypersons summary of results (for publication) | Final-v2_BO42452-CROSSWALK-a_Final-Analysis-LPS_19Jan2026_NL-NL | NA |
| Protocol (for publication) | D1_Protocol 2022-502546-26-00 Redacted | v5 |
| Protocol (for publication) | D4_Patient facing documents_NRS_ENG | 2 |
| Protocol (for publication) | D4_Patient facing documents_NRS_ES | 2 |
| Protocol (for publication) | D4_Patient facing documents_NRS_FR | 2 |
| Protocol (for publication) | D4_Patient facing documents_NRS_IT | 2 |
| Protocol (for publication) | D4_Patient facing documents_NRS_NL | 2 |
| Summary of results (for publication) | Study BO42452_CTIS Results Summary | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ENG 2022-502546-26-00 | 3 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ES 2022-502546-26-00 | NA |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_FR 2022-502546-26-00 | 3 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_IT 2022-502546-26-00 | 3 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_NL 2022-502546-26-00 | 3 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-06-16 | Netherlands | Acceptable 2023-07-21
|
2023-07-21 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-12-12 | Netherlands | Acceptable 2024-03-25
|
2024-03-25 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-06-21 | Netherlands | Acceptable 2024-08-12
|
2024-08-12 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-03-06 | Acceptable 2024-08-12
|
2025-03-06 | |
| 5 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-06-24 | Netherlands | Acceptable 2025-08-13
|
2025-08-13 |