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

Primary Purpose

Beta-Thalassemia, Thalassemia, Hematologic Diseases

Status

Recruiting

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

CTX001

About this trial

This is an interventional treatment trial for Beta-Thalassemia

Eligibility Criteria

12 Years - 35 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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 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

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 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.

Sites / Locations

Columbia University Medical CenterRecruiting
Atrium Health Levine Children's HospitalRecruiting
SCRI at the Children's Hospital at TriStar CentennialRecruiting
Universitätsklinikum Düsseldorf Hospital DuesseldorfRecruiting
Ospedale Pediatrico Bambino Gesù, IRCCS

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CTX001

Arm Description

CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Participants will receive a single infusion of CTX001 through a central venous catheter.

Outcomes

Primary Outcome Measures

Fetal Hemoglobin (HbF) Concentration Over Time

Total Hemoglobin (Hb) Concentration Over Time

Secondary Outcome Measures

TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

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)

TDT and SCD: Time to Engraftment

TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion

TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion

TDT and SCD: Incidence of All-cause Mortality

TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions

TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time

TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time

TDT: Duration Transfusion Free in Participants

SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs)

SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs

SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs

SCD: Relative Reduction in Haptoglobin

SCD: Relative Reduction in Lactate dehydrogenase

SCD: Relative Reduction in Total Bilirubin

SCD: Relative Reduction in Indirect Bilirubin

Full Information

NCT ID

NCT05477563

First Posted

July 26, 2022

Last Updated

August 2, 2023

Sponsor

Vertex Pharmaceuticals Incorporated

Collaborators

CRISPR Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT05477563

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 2, 2022 (Actual)

Primary Completion Date

February 2025 (Anticipated)

Study Completion Date

February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vertex Pharmaceuticals Incorporated

Collaborators

CRISPR Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CTX001

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

CTX001

Other Intervention Name(s)

Exagamglogene autotemcel, Exa-cel

Intervention Description

Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan.

Primary Outcome Measure Information:

Title

Fetal Hemoglobin (HbF) Concentration Over Time

Time Frame

Up to 12 Months After CTX001 Infusion

Title

Total Hemoglobin (Hb) Concentration Over Time

Time Frame

Up to 12 Months After CTX001 Infusion

Secondary Outcome Measure Information:

Title

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

Title

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

Title

TDT and SCD: Time to Engraftment

Time Frame

Up to 12 Months After CTX001 Infusion

Title

TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion

Time Frame

Within 100 Days After CTX001 Infusion

Title

TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion

Time Frame

Within 12 Months After CTX001 Infusion

Title

TDT and SCD: Incidence of All-cause Mortality

Time Frame

From Signing of Informed Consent up to 12 Months After CTX001 Infusion

Title

TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions

Time Frame

From Day 60 up to 12 Months After CTX001 Infusion

Title

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

Title

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

Title

TDT: Duration Transfusion Free in Participants

Time Frame

Up to 12 Months After CTX001 Infusion

Title

SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs)

Time Frame