A study to learn about the safety and efficacy of CTX001 (the "study drug product") to treat beta-thalassemia in pediatric subjects

A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Transfusion-Dependent ß-Thalassemia

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-002172-39-DE

Enrollment

Registered

2021-10-01

Start date

2022-03-21

Completion date

Unknown

Last updated

2024-12-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Transfusion-Dependent ß Thalassemia MedDRA version: 20.1 Level: LLT Classification code 10054660 Term: Thalassemia beta System Organ Class: 10010331 - Congenital, familial and genetic disorders

Interventions

Product Name: Exagamglogene autotemcel (Exacel) Product Code: CTX001 Pharmaceutical Form: Dispersion for infusion INN or Proposed INN: Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem an

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Subjects 2 through 11 years of age, inclusive, on the date of informed consent. • Diagnosis of transfusion-dependent ß-thalassemia (TDT) as defined by: a. Documented homozygous or compound heterozygous ß-thalassemia including ß-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 start of busulfan conditioning. b. History of at least 100 mL/kg/year of packed RBC transfusions in the prior 24 months before signing of consent (or the last rescreening for patients going through repeat screening) or, for subjects initiating transfusion therapy =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: • An available 10/10 Human Leukocyte Antigen (HLA)-matched related donor. • Prior allo-HSCT. • Subjects with associated a-thalassemia and >1 alpha chain 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 <150 × 10^9/L not related to hypersplenism. Other protocol defined exclusion criteria may apply.

Design outcomes

Primary

Measure	Time frame
Main Objective: Evaluate the efficacy of a single dose of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs; CTX001) in pediatric subjects with Transfusion-Dependent ß-Thalassemia (TDT);Secondary Objective: • Evaluate the safety and tolerability of a single dose of CTX001 • Quantify percentage of edited alleles in peripheral blood and CD34+ cells of the bone marrow • Assess the production of HbF post-CTX001 infusion • Assess the effects of infusion of CTX001 on disease-specific events and clinical status;Primary end point(s): Proportion of subjects who achieve TI12. A subject will be considered to have achieved TI12 if he/she has maintained 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.;Timepoint(s) of evaluation of this end point: Up to 24 months	—

Measure

Time frame

Main Objective: Evaluate the efficacy of a single dose of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs; CTX001) in pediatric subjects with Transfusion-Dependent ß-Thalassemia (TDT);Secondary Objective: • Evaluate the safety and tolerability of a single dose of CTX001 • Quantify percentage of edited alleles in peripheral blood and CD34+ cells of the bone marrow • Assess the production of HbF post-CTX001 infusion • Assess the effects of infusion of CTX001 on disease-specific events and clinical status;Primary end point(s): Proportion of subjects who achieve TI12. A subject will be considered to have achieved TI12 if he/she has maintained 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.;Timepoint(s) of evaluation of this end point: Up to 24 months

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Secondary

Measure	Time frame
Secondary end point(s): • Safety and tolerability of CTX001 based on adverse events (AEs), clinical laboratory values, vital signs, neutrophil engraftment, platelet engraftment, transplant-related mortality (TRM), and all-cause mortality. • Proportion of subjects who achieve TI6. A subject will be considered to have achieved TI6 if he/she has maintained 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 reduction from baseline in annualized volume of RBC transfusions • Transfusion free duration for subjects who achieve TI12. • Proportion of alleles with intended genetic modification present in peripheral blood over time. • Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time. • HbF concentration (pre-transfusion) over time. • Total hemoglobin concentration (pre-transfusion) over time.;Timepoint(s) of evaluation of this end point: Up to 24 months	—

Measure

Time frame

Secondary end point(s): • Safety and tolerability of CTX001 based on adverse events (AEs), clinical laboratory values, vital signs, neutrophil engraftment, platelet engraftment, transplant-related mortality (TRM), and all-cause mortality. • Proportion of subjects who achieve TI6. A subject will be considered to have achieved TI6 if he/she has maintained 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 reduction from baseline in annualized volume of RBC transfusions • Transfusion free duration for subjects who achieve TI12. • Proportion of alleles with intended genetic modification present in peripheral blood over time. • Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time. • HbF concentration (pre-transfusion) over time. • Total hemoglobin concentration (pre-transfusion) over time.;Timepoint(s) of evaluation of this end point: Up to 24 months

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Countries

Canada, Germany, Italy, United Kingdom, United States

Contacts

Public ContactClinical Trials and Medical Info

Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com+1877634 8789

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026