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

Sickle Cell Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05477563
• Other study ID #: VX21-CTX001-161
• Secondary ID: 2021-006390-37
• Status: Recruiting
• Phase: Phase 3
• Start date: August 2, 2022
• Est. completion date: February 2025

Study information

• Verified date: March 2024
• Source: Vertex Pharmaceuticals Incorporated
• Contact: Medical Information
• Phone: 617-341-6777
• Email: medicalinfo[@]vrtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 26
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 35 Years

Eligibility

Key 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 ß-thalassemia or compound heterozygous ß-thalassemia including ß-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

Key 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 a-thalassemia and >1 alpha deletion, or alpha multiplications
• Participants with sickle cell ß-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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• beta-Thalassemia
• Genetic Diseases, Inborn
• Hematologic Diseases
• Hemoglobinopathies
• Sickle Cell Anemia
• Sickle Cell Disease
• Thalassemia

Intervention

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

Locations

Country	Name	City	State
Germany	Universitätsklinikum Düsseldorf Hospital Duesseldorf	Duesseldorf
Italy	Ospedale Pediatrico Bambino Gesù, IRCCS	Rome
United States	Atrium Health Levine Children's Hospital	Charlotte	North Carolina
United States	SCRI at the Children's Hospital at TriStar Centennial	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated	CRISPR Therapeutics

Countries where clinical trial is conducted

United States,  Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fetal Hemoglobin (HbF) Concentration Over Time		Up to 12 Months After CTX001 Infusion
Primary	Total Hemoglobin (Hb) Concentration Over Time		Up to 12 Months After CTX001 Infusion
Secondary	TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		From Signing of Informed Consent up to 12 Months After CTX001 Infusion
Secondary	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)		Within 42 Days After CTX001 Infusion
Secondary	TDT and SCD: Time to Engraftment		Up to 12 Months After CTX001 Infusion
Secondary	TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion		Within 100 Days After CTX001 Infusion
Secondary	TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion		Within 12 Months After CTX001 Infusion
Secondary	TDT and SCD: Incidence of All-cause Mortality		From Signing of Informed Consent up to 12 Months After CTX001 Infusion
Secondary	TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions		From Day 60 up to 12 Months After CTX001 Infusion
Secondary	TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time		Up to 12 Months After CTX001 Infusion
Secondary	TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time		Up to 12 Months After CTX001 Infusion
Secondary	TDT: Duration Transfusion Free in Participants		Up to 12 Months After CTX001 Infusion
Secondary	SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs)		From Baseline up to 12 Months After CTX001 Infusion
Secondary	SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs		From Baseline up to 12 Months After CTX001 Infusion
Secondary	SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs		From Baseline up to 12 Months After CTX001 Infusion
Secondary	SCD: Relative Reduction in Haptoglobin		From Baseline up to 12 Months After CTX001 Infusion
Secondary	SCD: Relative Reduction in Lactate dehydrogenase		From Baseline up to 12 Months After CTX001 Infusion
Secondary	SCD: Relative Reduction in Total Bilirubin		From Baseline up to 12 Months After CTX001 Infusion
Secondary	SCD: Relative Reduction in Indirect Bilirubin		From Baseline up to 12 Months After CTX001 Infusion