Beta-ThalassemiaPhase 3NCT05477563
Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease
A Phase 3 study testing CTX001 in people with Beta-Thalassemia and Thalassemia, run by Vertex Pharmaceuticals Incorporated at 6 sites in 4 countries.
Trial summary
This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001. Read more about this study
- Who is it for?
- Ages 12 to 35 years
- Conditions the study is for
- Beta-Thalassemia, Thalassemia, Hematologic Diseases
- What is being tested?
- CTX001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 2 Aug 2022to 9 Jun 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participants with TDT and SCD:
- Eligible for autologous stem cell transplant as per investigator's judgment.
- Participants with TDT:
- Diagnosis of TDT as defined by:
- Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Participants 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 milliliter (mL)/kilograms (kg)/year or 10 units/year of packed red blood cells (RBC) transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening
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- Participants with SCD:
- Diagnosis of severe SCD as defined by:
- Documented SCD genotypes
- History of at least two severe VOCs events per year for the previous two years prior to enrollment
Who cannot join
- Participants with TDT and SCD:
- A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement
- Prior hematopoietic stem cell transplant (HSCT)
- Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator
- Participants with TDT:
- Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications
Show all 10Show fewer
- Participants with sickle cell β-thalassemia variant
- Participants with SCD:
- History of untreated moyamoya syndrome or presence of moyamoya syndrome at screening
- Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
6 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
6 sites in 4 countries
United States3 sites, 3 recruiting
- Recruiting
Levine Children's Hospital - Hematology
Charlotte, North Carolina, 28203
- Recruiting
TriStar Medical Group Children's Specialists - Pediatric Oncology
Nashville, Tennessee, 37203
- Recruiting
New York Presbyterian Hospital - Morgan Stanley Children's Hospital
New York, New York, 10032
Germany1 site, 1 recruiting
- Recruiting
University Hospital Dusseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology
Düsseldorf
Italy1 site, 1 recruiting
- Recruiting
IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica
Rome
Saudi Arabia1 site, 1 recruiting
- Recruiting
King Faisal Specialist Hospital & Research Centre - Riyadh - Hematology
Al Mathar Ash Shamali
About this study
Official title: 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
This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001.
- Conditions
- Beta-Thalassemia, Thalassemia, Hematologic Diseases, Genetic Diseases, Inborn, Hemoglobinopathies, Sickle Cell Disease
- Being tested
- CTX001
- Medical subject headings
- beta-Thalassemia, Thalassemia, Hematologic Diseases, Genetic Diseases, Inborn, Hemoglobinopathies, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTX001Biological
Also called Exagamglogene autotemcel, Exa-cel
Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan
| Study group | Role | What they receive |
|---|---|---|
| CTX001 | Experimental | CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Participants will receive a single infusion of CTX001 through a central venous catheter. Receives: Biological: CTX001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fetal Hemoglobin (HbF) Concentration Over Time
Measured: Up to 12 Months After CTX001 Infusion
Total Hemoglobin (Hb) Concentration Over Time
Measured: Up to 12 Months After CTX001 Infusion
Secondary outcomes (17)
TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: From Signing of Informed Consent up to 12 Months After CTX001 Infusion
TDT and SCD: Proportion of Participants With Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count (ANC) >=500 per Microliter [mcgL] on 3 Different Days)
Measured: Within 42 Days After CTX001 Infusion
TDT and SCD: Time to Engraftment
Measured: Up to 12 Months After CTX001 Infusion
TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion
Measured: Within 100 Days After CTX001 Infusion
TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion
Measured: Within 12 Months After CTX001 Infusion
TDT and SCD: Incidence of All-cause Mortality
Measured: From Signing of Informed Consent up to 12 Months After CTX001 Infusion
TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions
Measured: From Day 60 up to 12 Months After CTX001 Infusion
TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time
Measured: Up to 12 Months After CTX001 Infusion
TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time
Measured: Up to 12 Months After CTX001 Infusion
TDT: Duration Transfusion Free in Participants
Measured: Up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs)
Measured: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs
Measured: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs
Measured: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Haptoglobin
Measured: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Lactate dehydrogenase
Measured: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Total Bilirubin
Measured: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Indirect Bilirubin
Measured: From Baseline up to 12 Months After CTX001 Infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2022
- Study start2 Aug 2022
- Primary completion9 Jun 2027 (estimated)
- Study completion9 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Beta-ThalassemiaStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05477563
- Sponsor's protocol ID
- VX21-CTX001-161
- Other IDs
- 2024-514641-12-00
- Status last verified
- Mar 2026
- First submitted
- 26 Jul 2022
- Last updated
- 23 Mar 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/our-science/clinical-trials-data-sharing/
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05477563
- Acronym / sponsor ID
- VX21-CTX001-161
- Conditions
- Beta-Thalassemia, Thalassemia, Hematologic Diseases, Genetic Diseases, Inborn, Hemoglobinopathies, Sickle Cell Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 2 Aug 2022 (actual)
- Primary completion
- 9 Jun 2027 (estimated)
- Study completion
- 9 Jun 2027 (estimated)
- First posted
- 28 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CTX001 | Experimental | Biological: CTX001CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Participants will receive a single infusion of CTX001 through a central venous catheter. |
Who may qualify
- Ages
- 12 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Participants with TDT and SCD:
- Eligible for autologous stem cell transplant as per investigator's judgment.
- Participants with TDT:
- Diagnosis of TDT as defined by:
- Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Participants can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning
Key exclusion criteria (10 listed)
- Participants with TDT and SCD:
- A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement
- Prior hematopoietic stem cell transplant (HSCT)
- Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator
- Participants with TDT:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CTX001Also: Exagamglogene autotemcel, Exa-celAdministered by intravenous (IV) infusion following myeloablative conditioning with busulfan | Biological | CTX001 |
Primary outcome
Fetal Hemoglobin (HbF) Concentration Over Time
Time frame: Up to 12 Months After CTX001 Infusion
Total Hemoglobin (Hb) Concentration Over Time
Time frame: Up to 12 Months After CTX001 Infusion
17 secondary outcomes
TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion
TDT and SCD: Proportion of Participants With Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count (ANC) >=500 per Microliter [mcgL] on 3 Different Days)
Time frame: Within 42 Days After CTX001 Infusion
TDT and SCD: Time to Engraftment
Time frame: Up to 12 Months After CTX001 Infusion
TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion
Time frame: Within 100 Days After CTX001 Infusion
TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion
Time frame: Within 12 Months After CTX001 Infusion
TDT and SCD: Incidence of All-cause Mortality
Time frame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion
TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions
Time frame: From Day 60 up to 12 Months After CTX001 Infusion
TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time
Time frame: Up to 12 Months After CTX001 Infusion
TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time
Time frame: Up to 12 Months After CTX001 Infusion
TDT: Duration Transfusion Free in Participants
Time frame: Up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs)
Time frame: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs
Time frame: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs
Time frame: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Haptoglobin
Time frame: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Lactate dehydrogenase
Time frame: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Total Bilirubin
Time frame: From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Indirect Bilirubin
Time frame: From Baseline up to 12 Months After CTX001 Infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2026.
- Individual participant dataSharing planned: No. Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/our-science/clinical-trials-data-sharing/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CTX001 in people with Beta-Thalassemia and Thalassemia, run by Vertex Pharmaceuticals Incorporated at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Germany, Italy, Saudi Arabia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Medical Information (6173416777, medicalinfo@vrtx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fetal Hemoglobin (HbF) Concentration Over Time (time frame: Up to 12 Months After CTX001 Infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2026.