Clinical trial NCT05356195: Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent β-Thalassemia (TDT)
Official title: A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Transfusion-Dependent β-Thalassemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Beta-Thalassemia
Thalassemia
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
Collaborators: name: CRISPR Therapeutics
First posted: 2022-05-02
Enrollment: 15
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-dose, open-label study in pediatric participants with TDT. The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (CTX001).


Eligibility criteria: Key Inclusion Criteria:

* Diagnosis of TDT as defined by:

  * Documented homozygous 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 mL/kilograms (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 participants initiating transfusion therapy \<24 months before signing of consent, requirement for packed RBC transfusion at least every 3 to 4 weeks for ≥6 months
* Eligible for autologous stem cell transplant as per investigator's judgment.

Key Exclusion Criteria:

* 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)
* Participants with associated α-thalassemia and \>1 alpha deletion, or alpha multiplications
* Participants with sickle cell β-thalassemia variant
* Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator

Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Proportion of Participants who Achieve Transfusion Independence for at Least 12 Consecutive Months (TI12)
timeFrame: Up to 24 Months After CTX001 Infusion
Secondary outcomes:
measure: Proportion of Participants Achieving at Least 95 Percent (%), 90%, 85%, 75% and 50% Reduction in Annualized Transfusions
timeFrame: From Baseline up to 24 Months After CTX001 Infusion
measure: Transfusion Free Duration for Participants who Achieve TI12
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Change in Fetal Hemoglobin Concentration Over Time
timeFrame: From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion
measure: Change in Total Hemoglobin Concentration Over Time
timeFrame: From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Signing of Informed Consent up to 24 Months After CTX001 Infusion
measure: Proportion of Participants With Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count [ANC] ≥500 per Microliter [mcgL] on 3 Different Days)
timeFrame: Within 42 Days After CTX001 Infusion
measure: Time to Engraftment
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Incidence of Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion
timeFrame: Within 100 Days After CTX001 Infusion
measure: Incidence of TRM Within 12 Months After CTX001 Infusion
timeFrame: Within 12 Months After Infusion
measure: Incidence of All-cause Mortality
timeFrame: From Signing of Informed Consent up to 24 Months After CTX001 Infusion
measure: Relative Reduction in Annualized Volume and Episodes of RBC Transfusions starting Month 10 After CTX001 infusion
timeFrame: From Baseline up to 24 Months After CTX001 Infusion
Other outcomes:
Locations:
city: Nashville
country: United States
facility: SCRI at the Children's Hospital at TriStar Centennial
state: Tennessee
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf Hospital Duesseldorf
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù, IRCCS
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Foundation Trust
city: London
country: United Kingdom
facility: St Mary's Hospital
Study officials:
References: