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Recruiting NCT05477563

Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease

Phase III Interventional Beta-Thalassemia Thalassemia Hematologic Diseases Genetic Diseases, Inborn

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: CTX001.
Who it may be relevant to
Registry conditions: Beta-Thalassemia, Thalassemia, Hematologic Diseases, Genetic Diseases, Inborn. Basic parameters: 12 years — 35 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Germany, Italy, Saudi Arabia
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease

Overview

This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001.

Interventions

  • Biological CTX001
    Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan

Primary outcome measures

  • Fetal Hemoglobin (HbF) Concentration Over Time [Time frame: Up to 12 Months After CTX001 Infusion]
  • Total Hemoglobin (Hb) Concentration Over Time [Time frame: Up to 12 Months After CTX001 Infusion]
Secondary outcome measures (12)
  • TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion]
  • TDT and SCD: Proportion of Participants With Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count (ANC) >=500 per Microliter [mcgL] on 3 Different Days) [Time frame: Within 42 Days After CTX001 Infusion]
  • TDT and SCD: Time to Engraftment [Time frame: Up to 12 Months After CTX001 Infusion]
  • TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion [Time frame: Within 100 Days After CTX001 Infusion]
  • TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion [Time frame: Within 12 Months After CTX001 Infusion]
  • TDT and SCD: Incidence of All-cause Mortality [Time frame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion]
  • TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions [Time frame: From Day 60 up to 12 Months After CTX001 Infusion]
  • TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time [Time frame: Up to 12 Months After CTX001 Infusion]
  • TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time [Time frame: Up to 12 Months After CTX001 Infusion]
  • TDT: Duration Transfusion Free in Participants [Time frame: Up to 12 Months After CTX001 Infusion]
  • SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs) [Time frame: From Baseline up to 12 Months After CTX001 Infusion]
  • SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs [Time frame: From Baseline up to 12 Months After CTX001 Infusion]

Eligibility criteria

Inclusion criteria

  • Participants with TDT and SCD:
  • Eligible for autologous stem cell transplant as per investigator's judgment.
  • Participants with TDT:
  • Diagnosis of TDT as defined by:
  • 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
  • History of at least 100 milliliter (mL)/kilograms (kg)/year or 10 units/year of packed red blood cells (RBC) transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening
  • Participants with SCD:
  • Diagnosis of severe SCD as defined by:
  • Documented SCD genotypes
  • History of at least two severe VOCs events per year for the previous two years prior to enrollment

Exclusion criteria

  • Participants with TDT and SCD:
  • 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)
  • Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator
  • Participants with TDT:
  • Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications
  • Participants with sickle cell β-thalassemia variant
  • Participants with SCD:
  • History of untreated moyamoya syndrome or presence of moyamoya syndrome at screening

Other protocol defined Inclusion/Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 3 centers
  • New York Presbyterian Hospital - Morgan Stanley Children's Hospital — New York
  • Levine Children's Hospital - Hematology — Charlotte
  • TriStar Medical Group Children's Specialists - Pediatric Oncology — Nashville
Germany · 1 center
  • University Hospital Dusseldorf - Department of Pediatric Oncology, Hematology and Clinical — Düsseldorf
Italy · 1 center
  • IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellula — Rome
Saudi Arabia · 1 center
  • King Faisal Specialist Hospital & Research Centre - Riyadh - Hematology — Al Mathar Ash Shamali

Identifiers

NCT: NCT05477563 · VX21-CTX001-161 · 2024-514641-12-00

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗