A Safety and Efficacy Study Evaluating CTX001 in Participants With Transfusion-Dependent β-Thalassemia

Vertex Pharmaceuticals Incorporated59 enrolled

Overview

This is a single-arm, open-label, multi-site, single-dose Phase 1/2/3 study in participans 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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Beta-Thalassemia Thalassemia Genetic Diseases, Inborn Hematologic Diseases Hemoglobinopathies

Interventions

CTX001BIOLOGICAL

Administered by IV infusion following myeloablative conditioning with busulfan

Eligibility

Sex: ALLMin age: 12 YearsMax age: 35 Years

Medical Language ↔ Plain English

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). 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 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 * Participants with associated α-thalassemia and \>1 alpha deletion or alpha multiplications * Participants 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.

Locations (14)

Lucile Packard Children's Hospital

Palo Alto, California, United States

Ann & Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Outcomes

Primary Outcomes

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

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

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

Time frame: Within 42 days after CTX001 infusion

Time to neutrophil and platelet engraftment

Time frame: Days post-infusion to engraftment

Frequency and severity of collected adverse events (AEs)

Time frame: Signing of informed consent through Month 24 visit

Incidence of transplant-related mortality (TRM)

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

All-cause mortality

Time frame: Signing of informed consent through Month 24 visit

Secondary Outcomes

Proportion of participants achieving transfusion independence for at least 6 consecutive months (TI6)

Time frame: From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion

Proportion of participants achieving at least 95 percent (%), 90%, 85%, 75%, and 50% reduction from baseline in annualized volume of RBC transfusions after Month 10 after CTX001 infusion

Time frame: From Month 10 up to 24 months post-CTX001 infusion

Relative reduction from baseline in annualized volume of RBC transfusions after Month 10 after CTX001 infusion

Data from ClinicalTrials.gov

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Columbia University Medical Center (21+ years)

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers

Nashville, Tennessee, United States

The Hospital for Sick Children

Toronto, Canada

British Columbia Children's Hospital

Vancouver, Canada

Universitätsklinikum Düsseldorf Hospital Duesseldorf

Düsseldorf, Germany

Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine

Regensburg, Germany

...and 4 more locations

Time frame: From Month 10 up to 24 months post-CTX001 infusion

Duration of transfusion free in participants who have achieved TI12

Time frame: From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion

Proportion of alleles with intended genetic modification in peripheral blood leukocytes over time

Time frame: Day 1 CTX001 infusion through Month 24 visit

Proportion of alleles with intended genetic modification present in CD34+ cells of bone marrow over time

Time frame: Day 1 CTX001 infusion through Month 24 visit

Change in fetal hemoglobin concentration over time

Time frame: Baseline (pre-transfusion) through Month 24 visit

Change in total hemoglobin concentration over time

Time frame: Baseline (pre-transfusion) through Month 24 visit

Change in health-related quality of life (HRQoL) from baseline over time using EuroQol Questionnaire (5 dimensions - 5 levels of severity - EQ-5D-5L)

The EQ-5D-5L Questionnaire consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The EQ-5D comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and 5 levels: no problems to extreme problems. The subject marks the most appropriate statement in each dimension, resulting in a 1-digit number for that dimension. The digits can be combined in a 5-digit number describing the subject's health state. The EQ VAS records the subject's self-rated health on a 100-point VAS, endpoints labelled "the best health you can imagine" and "the worst health you can imagine."