Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
17
Countries
1
Sites
3
Transfusion-dependent β-thalassemia (TDT)
To evaluate the safety and efficacy of a single dose of autologous CRISPR-Cas9 modified CD34+ hHSPCs (CTX001) in subjects with TDT
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
- 7 Sep 2018 → 13 Nov 2025
- Decision date (initial)
- 2024-09-13
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-516894-57-00
- EudraCT number
- 2017-003351-38
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
To evaluate the safety and efficacy of a single dose of autologous CRISPR-Cas9 modified CD34+ hHSPCs (CTX001) in subjects with TDT
Secondary objectives 3
- To quantify percentage of edited alleles in peripheral blood leukocytes and CD34+ cells of the bone marrow
- To assess the production of HbF post-CTX001 infusion
- To assess the effects of infusion of CTX001 on disease-specific events and clinical status
Conditions and MedDRA coding
Transfusion-dependent β-thalassemia (TDT)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | LLT | 10054660 | Thalassemia beta | 10010331 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Diagnosis of transfusion-dependent β-thalassemia (TDT) as defined by: Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Subjects can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning.
- History of at least 100 mL/kg/year or ≥10 units/year of packed RBC transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening.
- Eligible for autologous stem cell transplant as per investigator's judgment.
Exclusion criteria 7
- A willing and healthy 10/10 Human Leukocyte Antigen (HLA)-matched related donor is available per investigator's judgement.
- Prior allo-HSCT.
- Subjects with associated α-thalassemia and >1 alpha deletion or alpha multiplications.
- Subjects with sickle cell beta thalassemia variant.
- Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
- White blood cell (WBC) count <3 × 10^9/L or platelet count <50 × 10^9/L not related to hypersplenism.
- Other protocol defined Inclusion/Exclusion criteria may apply.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 7
- Successful neutrophil engraftment
- Time to neutrophil engraftment
- Time to platelet engraftment
- Safety and tolerability assessments based on adverse events (AEs ), clinical laboratory values, and vital signs
- Incidence of transplant related mortality (TRM) within 100 days and within 1 year post-CTX001 infusion
- All-cause mortality
- Proportion of subjects achieving TI12, defined as maintaining weighted average Hb ≥9 g /dL without RBC transfusions for at least 12 consecutive months any time after CTX001 infusion. The evaluation of TI12 starts 60 days after last RBC transfusion for post-transplant support or TDT disease management.
Secondary endpoints 11
- Proportion of subjects achieving TI6, defined as maintaining weighted average Hb ≥9 g /dL without RBC transfusions for at least 6 consecutive months any time after CTX001 infusion. The evaluation of TI6 starts 60 days after last RBC transfusion for post-transplant support or TDT disease management.
- Proportion of subjects achieving at least 95%, 90%, 85%, 75%, 50% reduction from baseline in annualized transfusions up to 24 months starting 60 days after CTX001 infusion.
- Relative change from baseline in transfusions up to 24 months starting 60 days after CTX001 infusion
- Duration of transfusion free in subjects who have achieved TI12
- Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time. Intended genetic modifications are indels that modify the sequence of the erythrocyte-specific enhancer in intron 2 of BCL11A
- Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time
- Fetal hemoglobin concentration (pre-transfusion) over time
- Total hemoglobin concentration (pre-transfusion) over time
- Change in patient reported outcomes (PROs) over time using EuroQol Quality of Life Scale (EQ-5D-5L for subjects ≥18 years old, EQ-5D-Y for subjects <18 years old), functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) for subjects ≥18 years old, and Pediatric Quality of Life Inventory (PedsQL) for subjects <18 years old.
- Change in parameters of iron overload, including: o Liver iron concentration (LIC ) from baseline as assessed by R2 magnetic resonance imaging (MRI ) and cardiac iron content (CIC ) from baseline as assessed by T2 * MRI o Change in serum ferritin level from baseline over time
- Proportion of subjects receiving iron chelation therapy over time
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 USE
- 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
Auxiliary 3
SUB28849 · Substance
- Active substance
- Plerixafor
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 0.24 mg/kg milligram(s)/kilogram
- Max total dose
- 0.96 mg/kg milligram(s)/kilogram
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07627MIG · Substance
- Active substance
- Filgrastim
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 10 µg/Kg microgram(s)/kilogram
- Max total dose
- 60 µg/Kg microgram(s)/kilogram
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB05993MIG · Substance
- Active substance
- Busulfan
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 4.4 mg/kg milligram(s)/kilogram
- Max total dose
- 17.6 mg/kg milligram(s)/kilogram
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- 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
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ended | 5 | 3 |
| Rest of world
United Kingdom, United States, Canada
|
— | 12 | — |
Investigational sites
Universitaetsklinikum Regensburg AöR
Pediatric Hematology, Oncology and Stem cell transplantation, Franz-Josef-Strauss-Allee 11, Grass-Oberisling, Regensburg
Universitaetsklinikum Duesseldorf AöR
Department of Pediatric Oncology, Hematology and Clinical Immunology, Moorenstrasse 5, Bilk, Duesseldorf
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 |
|---|---|---|---|---|---|
| Germany | 2018-09-07 | 2025-10-10 | 2018-09-10 | 2021-09-28 |
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 |
|---|---|---|---|
| CTX001-111 Summary of Primary Results SUM-133398
|
2026-05-11T15:41:50 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| CTX001-111 Results Plain Language Summary_English | 2026-05-11T15:42:30 | Submitted | Laypersons Summary of Results |
| CTX001-111 Results Plain Language Summary_German | 2026-05-25T16:52:51 | Submitted | Laypersons Summary of Results |
| CTX001-111 Results Plain Language Summary_Italian | 2026-05-25T16:53:16 | Submitted | Laypersons Summary of Results |
Documents 14 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | CTX001-111 Results Plain Language Summary_English | 1 |
| Laypersons summary of results (for publication) | CTX001-111 Results Plain Language Summary_German | 1 |
| Laypersons summary of results (for publication) | CTX001-111 Results Plain Language Summary_Italian | 1 |
| Protocol (for publication) | D1_Protocol 2024-516894-57-00_Redacted | 6.9 |
| Protocol (for publication) | D4_Patient facing documents_EQ-5D_Placeholder | N/A |
| Protocol (for publication) | D4_Patient facing documents_FACT-BMT_Placeholder | N/A |
| Protocol (for publication) | D4_Patient facing documents_PesdsQL_Placeholder | N/A |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_Placeholder Statement | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adolescent_Germany_de | 8.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Adult_Germany_de_redacted | 15.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Parent_Germany_de_redacted | 7.0 |
| Summary of results (for publication) | CTX001-111 Summary of Primary Results_28Apr2026 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis en_2024-516894-57-00_Redacted | 6.9 |
| Synopsis of the protocol (for publication) | D1_Protocol_synopsis de_2024-516894-57-00_Redacted | 6.9 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-02 | Germany | Acceptable with conditions 2024-09-12
|
2024-09-13 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-02-03 | Germany | Acceptable 2025-04-01
|
2025-04-01 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-08-08 | Germany | Acceptable 2025-04-01
|
2025-08-08 |