Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
90
Countries
3
Sites
5
Sickle Cell Disease
Evaluate long-term safety of CTX001 in subjects who received CTX001 for treatment of transfusion-dependent thalassemia (TDT) or severe sickle cell disease (SCD)
Key facts
- Sponsor
- Vertex Pharmaceuticals Inc.
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 6 Mar 2020 → ongoing
- Decision date (initial)
- 2024-06-05
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-512654-19-00
- EudraCT number
- 2018-002935-88
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
Evaluate long-term safety of CTX001 in subjects who received CTX001 for treatment of transfusion-dependent thalassemia (TDT) or severe sickle cell disease (SCD)
Secondary objectives 1
- To evaluate efficacy of CTX001 up to 5 years after CTX001 infusion, in subjects who received CTX001 for treatment of TDT or SCD
Conditions and MedDRA coding
Sickle Cell Disease
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 22.0 | LLT | 10081904 | Transfusion dependent thalassemia | 10010331 |
| 21.0 | PT | 10040641 | Sickle cell anaemia | 100000004850 |
Regulatory references
- Plan to share IPD
- No
- IPD plan description
- Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing
| EU CT number | Title | Sponsor |
|---|---|---|
| 2021-006390-37 | A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects with Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease, Studio di fase 3b per valutare l’efficacia e la sicurezza di una dose singola di cellule staminali ematopoietiche e progenitrici umane autologhe, CD34+, modificate con CRISPR Cas9 (CTX001) in soggetti affetti da ß-talassemia trasfusione-dipendente o anemia falciforme grave. | |
| 2021-002173-26 | A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Severe Sickle Cell Disease, Studio di Fase 3 per valutare la sicurezza e l’efficacia di una dose singola di CTX001 in soggetti pediatrici affetti da malattia a cellule falciformi grave | |
| 2021-002172-39 | A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Transfusion-Dependent ß-Thalassemia, Studio di fase 3 per valutare la sicurezza e l'efficacia di una dose singola di CTX001 in soggetti pediatrici affetti da ß-talassemia trasfusione dipendente | |
| 2023-503247-34-00 | A Phase 3 Study to Evaluate Efficacy and Safety of a Single Dose of Exa-cel in Subjects with Severe Sickle Cell Disease, βS/βC Genotype | Vertex Pharmaceuticals Inc. |
| 2018-001320-19 | A Phase 1/2 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Severe Sickle Cell Disease, Studio di fase 1/2 per valutare la sicurezza e l’efficacia di una dose singola di cellule staminali ematopoietiche e progenitrici umane autologhe, CD34+, modificate con CRISPR-Cas9 (CTX001) in soggetti affetti da malattia a cellule falciformi grave | |
| 2017-003351-38 | A Phase 1/2 Study of the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) in Subjects with Transfusion-Dependent β Thalassemia |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 2
- Subjects or legal representative or guardian (if applicable) must sign and date informed consent form (ICF).
- Subjects must have received CTX001 infusion.
Exclusion criteria 1
- There are no exclusion criteria.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 5
- New Malignancies
- New or worsening hematologic disorders (e.g. immune-mediated cytopenias, aplastic anemia, primary immunodeficiencies)
- All-cause mortality
- All serious adverse events (SAEs) occurring up to 15 years after CTX001 infusion
- CTX001-related AE's
Secondary endpoints 5
- TDT and SCD: Total Hemoglobin (Hb) concentration over time
- TDT and SCD: Fetal Hemoglobin (HbF) concentration over time
- TDT and SCD: Proportion of alleles with intended genetic modification present in peripheral blood over time
- TDT and SCD: Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time
- TDT and SCD: Change in patient-reported outcome (PRO) over time in participants ≥18 years of age assessed using EuroQol quality of life scale (EQ-5D-5L) for participants from study 111,121 and 171 only
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Casgevy 4 - 13 x 10^6 cells/mL dispersion for infusion
PRD11151564 · Product
- Active substance
- Exagamglogene Autotemcel
- Substance synonyms
- AUTOLOGOUS CD34+ HEMATOPOIETIC STEM CELLS WITH A CRISPR-EDITED ERYTHROID ENHANCER REGION OF THE BCL11A GENE, CTX001
- Pharmaceutical form
- DISPERSION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 20 Other
- Max total dose
- 20 Other
- Max treatment duration
- 1 Week(s)
- Authorisation status
- Authorised
- ATC code
- B06AX05 — -
- Marketing authorisation
- EU/1/23/1787/001
- MA holder
- VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/19/2210
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Vertex Pharmaceuticals Inc.
- Sponsor organisation
- Vertex Pharmaceuticals Inc.
- Address
- 50 Northern Avenue
- City
- Boston
- Postcode
- 02210-1862
- Country
- United States
Scientific contact point
- Organisation
- Vertex Pharmaceuticals Inc.
- Contact name
- Clinical Trials and Medical Info
Public contact point
- Organisation
- Vertex Pharmaceuticals Inc.
- Contact name
- Clinical Trials and Medical Info
Locations
3 EU/EEA countries · 5 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruiting | 5 | 1 |
| Germany | Ongoing, recruiting | 16 | 3 |
| Italy | Ongoing, recruiting | 16 | 1 |
| Rest of world
United Kingdom, Canada, United States
|
— | 53 | — |
Investigational sites
Association Hospitaliere De Bruxelles Hopital Universitaire Des Enfants Reine Fabiola
Pediatric Hemato-Oncology, Jean Joseph Crocqlaan 15, 1020, Brussels
Universitaetsklinikum Duesseldorf AöR
Department of Pediatric Oncology, Hematology and Clinical Immunology, Moorenstrasse 5, Bilk, Duesseldorf
Universitaetsklinikum Regensburg AöR
Pediatric Hematology, Oncology and Stem cell transplantation, Franz-Josef-Strauss-Allee 11, Grass-Oberisling, Regensburg
Universitaetsklinikum Tuebingen AöR
Department of Hematology, Oncology and Pediatrics, Hoppe-Seyler-Strasse 1, Nordstadt, Tuebingen
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 |
|---|---|---|---|---|---|
| Belgium | 2024-06-26 | 2024-07-09 | |||
| Germany | 2020-04-23 | 2021-01-20 | |||
| Italy | 2020-03-06 | 2022-11-07 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Corrective measures 1 · Art. 77 CTR
Corrective measure CM-IT-0001
- Member state
- Italy
- Publication date
- 2025-07-09
- Type
- 1
- Reason
- 6
- Reverted date
- 2025-07-09
- Immediate action required
- Yes
- Notes
- Reverted (2025-07-09)
- Justification
- Dear Applicant
Considering the expiration of the three-year mandate of the members of the National Ethics Committee (CEN) for clinical trials relating to advanced therapies (“ATMP”) and of the National Ethics Committee (CEN) for clinical trials in the pediatric field, appointed by Decree of the Minister of Health - 2 March 2022;
Considering the fact that, due to the expiration of the mandate of the members of the aforementioned National Ethics Committee (CEN), for the procedure in subject the assessment of the aspects relating to Part II of the evaluation report pursuant to art. 7 of the aforementioned Regulation (EU) No. 536/2014 has not been carried out, and as a result there is no conclusion of Part II for the SM-1 EU CT 2024-512654-19-00 procedure (AIFA authorization provision n° 0054451-05/05/2025-AIFA-AIFA-P).
In compliance with CHAPTER XIII (SUPERVISION BY MEMBER STATES, UNION INSPECTIONS AND CONTROLS) of Regulation 536/2014 with specific reference to Article 77 (Corrective measures to be taken by Member States):
1. Where a Member State concerned has justified grounds for considering that the requirements set out in this Regulation are no longer met, it may take the following measures on its territory:
(a) revoke the authorisation of a clinical trial;
(b) suspend a clinical trial;
(c) require the sponsor to modify any aspect of the clinical trial.
A corrective measure is applied suspending the trial. This corrective measure is only applicable to Italy.
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 86 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-512654-19-00_Redacted | 6.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Emotional Impact short form_ar | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Emotional Impact_de | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Emotional Impact_en | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Emotional Impact_fr-BE | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Emotional Impact_it | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Med History Checklist_de | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Med History Checklist_fr-BE | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Med History Checklist_it | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Pain Episode Frequency_de | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Pain Episode Frequency_fr-BE | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Pain Episode Frequency_it | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Pain Impact short form_ar | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Pain Impact_de | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Pain Impact_fr-BE | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Pain Impact_it | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Pain Rating Scale_de | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Pain Rating Scale_fr-BE | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Pain Rating Scale_it | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Sleep Impact short form_ar | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Sleep Impact_de | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Sleep Impact_fr-BE | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Sleep Impact_it | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Social Functioning Impact_ar | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Social Functioning Impact_de | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Social Functioning Impact_fr-BE | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Social Functioning Impact_it | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Stiffness Impact short form_ar | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Stiffness Impact_de | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Stiffness Impact_fr_BE | 2.0 |
| Protocol (for publication) | D4_ Patient facing documents questionnaire Stiffness Impact_it | 2.0 |
| Protocol (for publication) | D4_Patient facing documents questionnaire Faces Pain Rating Scale_de | N/A |
| Protocol (for publication) | D4_Patient facing documents questionnaire Faces Pain Rating Scale_en | 2.0 |
| Protocol (for publication) | D4_Patient facing documents questionnaire Faces Pain Rating Scale_it | N/A |
| Protocol (for publication) | D4_Patient facing documents questionnaire Med History Checklist_en | 2.0 |
| Protocol (for publication) | D4_Patient facing documents questionnaire Pain Episode Frequency_en | 2.0 |
| Protocol (for publication) | D4_Patient facing documents questionnaire Pain Impact_en | 2.0 |
| Protocol (for publication) | D4_Patient facing documents questionnaire Pain Rating Scale_en | 2.0 |
| Protocol (for publication) | D4_Patient facing documents questionnaire Sleep Impact_en | 2.0 |
| Protocol (for publication) | D4_Patient facing documents questionnaire Social Functioning Impact_en | 2.0 |
| Protocol (for publication) | D4_Patient facing documents questionnaire Stiffness Impact_en | 2.0 |
| Protocol (for publication) | D4_Patient facing documents_FACT-BMT_Placeholder | N/A |
| Protocol (for publication) | D4_Patient facing documents_PedsQL_Placeholder | N/A |
| Protocol (for publication) | D4_Patient facing documents_questionnaire EQ-5D_Placeholder | N/A |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_Belgium | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_Germany | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_Italy | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adolescent SCD_Germany_de | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adolescent SCD_Italy_it_redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adolescent TDT_Germany_de | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adolescent TDT_Italy_it_redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult Privacy _Italy_it redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult SCD_Belgium_EN_redacted | 9.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult SCD_Belgium_FR_redacted | 9.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult SCD_Germany_de_redacted | 8.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult SCD_Italy_it_redacted | 8.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult TDT_Germany_de_redacted | 8.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult TDT_Italy_it_redacted | 8.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Child SCD_Germany_de | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Child SCD_Italy_it | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Child TDT_Germany_de | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Child TDT_Italy_it | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Greenphire_Belgium_EN | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Greenphire_Belgium_FR | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Greenphire_Germany_de | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Limited Follow-up_Italy_it | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Limited FUP_Belgium_EN_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Limited FUP_Belgium_FR_Redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Limited FUP_Germany_de | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Parent Privacy _Italy_it_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Parent SCD_Germany_de_redacted | 8.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Parent SCD_Italy_it_redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Parent TDT_Germany_de_redacted | 8.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Parent TDT_Italy_it_redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnancy_Belgium_EN_redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnancy_Belgium_FR_redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnancy_Germany_de | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnancy_Italy_it | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Greenphire_Italy_IT | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_GP Letter Italy_it | 2.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis en_2024-512654-19-00 | 6.0 |
| Synopsis of the protocol (for publication) | D1_Protocol_synopsis de-BE 2024-512654-19-00 | 6.0 |
| Synopsis of the protocol (for publication) | D1_Protocol_synopsis de-DE 2024-512654-19-00 | 6.0 |
| Synopsis of the protocol (for publication) | D1_Protocol_synopsis fr-BE 2024-512654-19-00 | 6.0 |
| Synopsis of the protocol (for publication) | D1_Protocol_synopsis it_2024-512654-19-00 | 6.0 |
| Synopsis of the protocol (for publication) | D1_Protocol_synopsis nl-BE 2024-512654-19-00 | 6.0 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-05-09 | Germany | Acceptable 2024-06-04
|
2024-06-05 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-01-17 | Germany | Acceptable 2025-04-28
|
2025-04-28 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-08-08 | Germany | Acceptable 2025-04-28
|
2025-08-08 |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-09-10 | Germany | Acceptable 2025-11-10
|
2025-11-10 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2026-03-02 | Germany | Acceptable 2025-11-10
|
2026-03-02 |