Clinical trial

A Phase 1/2/3 Study of the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) in Subjects With Transfusion-Dependent β-Thalassemia

Name

CTX001-111

Description

This is a single-arm, open-label, multi-site, single-dose Phase 1/2/3 study in subjects with transfusion-dependent β-thalassemia (TDT). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) using CTX001.

Trial arms

Trial start

2018-09-14

Estimated PCD

2024-08-01

Trial end

2024-08-01

Status

Active (not recruiting)

Phase

Early phase I

Treatment

CTX001

Administered by IV infusion following myeloablative conditioning with busulfan

Arms:

CTX001

Other names:

Exagamglogene autotemcel, Exa-cel

Size

Primary endpoint

Proportion of subjects achieving transfusion independence for at least 12 consecutive months (TI12)

From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion]

Proportion of subjects with engraftment (first day of 3 consecutive measurements of absolute neutrophil count [ANC] ≥500/µL on three different days)

Within 42 days after CTX001 infusion

Time to neutrophil and platelet engraftment

Days post-infusion to engraftment

Frequency and severity of collected adverse events (AEs)

Signing of informed consent through Month 24 visit

Incidence of transplant-related mortality (TRM)

Baseline (pre-transfusion) to 100 days and 1 year post-CTX001 infusion

All-cause mortality

Signing of informed consent through Month 24 visit

Eligibility criteria

Key Inclusion Criteria: * Diagnosis of transfusion-dependent β-thalassemia (TDT) as defined by: 1. 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. 2. 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. Key Exclusion Criteria: * 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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2', 'PHASE3'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 45, 'type': 'ESTIMATED'}}

Updated at

2023-12-22

1 organization

1 product

6 indications

Organization

Vertex Pharmaceuticals

Product

CTX001

Indication

Beta Thalassemia

Indication