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

Phase 1

• Conditions: Transfusion-Dependent ß Thalassemia; MedDRA version: 20.1Level: LLTClassification code 10054660Term: Thalassemia betaSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2021-002172-39-IT
• Lead Sponsor: VERTEX PHARMACEUTICALS INCORPORATED

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-06
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 12

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 <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.
Other protocol defined inclusion criteria may apply.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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);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;Secondary Objective: • Evaluate the safety and tolerability of a single dose of CTX001<br>• Quantify percentage of edited alleles in peripheral blood and CD34+ cells of the bone marrow<br>• Assess the production of HbF post-CTX001 infusion<br>• Assess the effects of infusion of CTX001 on disease-specific events and clinical status