Clinical trial NCT05477563: 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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Beta-Thalassemia
Thalassemia
Hematologic Diseases
Genetic Diseases, Inborn
Hemoglobinopathies
Sickle Cell Disease
Sickle Cell Anemia
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2022-07-28
Enrollment: 26
Sex: ALL
Minimum age (years): 12
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Fetal Hemoglobin (HbF) Concentration Over Time
timeFrame: Up to 12 Months After CTX001 Infusion
measure: Total Hemoglobin (Hb) Concentration Over Time
timeFrame: Up to 12 Months After CTX001 Infusion
Secondary outcomes:
measure: TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion
measure: 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)
timeFrame: Within 42 Days After CTX001 Infusion
measure: TDT and SCD: Time to Engraftment
timeFrame: Up to 12 Months After CTX001 Infusion
measure: TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion
timeFrame: Within 100 Days After CTX001 Infusion
measure: TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion
timeFrame: Within 12 Months After CTX001 Infusion
measure: TDT and SCD: Incidence of All-cause Mortality
timeFrame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion
measure: TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions
timeFrame: From Day 60 up to 12 Months After CTX001 Infusion
measure: TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time
timeFrame: Up to 12 Months After CTX001 Infusion
measure: TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time
timeFrame: Up to 12 Months After CTX001 Infusion
measure: TDT: Duration Transfusion Free in Participants
timeFrame: Up to 12 Months After CTX001 Infusion
measure: SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs)
timeFrame: From Baseline up to 12 Months After CTX001 Infusion
measure: SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs
timeFrame: From Baseline up to 12 Months After CTX001 Infusion
measure: SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs
timeFrame: From Baseline up to 12 Months After CTX001 Infusion
measure: SCD: Relative Reduction in Haptoglobin
timeFrame: From Baseline up to 12 Months After CTX001 Infusion
measure: SCD: Relative Reduction in Lactate dehydrogenase
timeFrame: From Baseline up to 12 Months After CTX001 Infusion
measure: SCD: Relative Reduction in Total Bilirubin
timeFrame: From Baseline up to 12 Months After CTX001 Infusion
measure: SCD: Relative Reduction in Indirect Bilirubin
timeFrame: From Baseline up to 12 Months After CTX001 Infusion
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Atrium Health Levine Children's Hospital
state: North Carolina
city: Nashville
country: United States
facility: TriStar Medical Group Children's Specialist
state: Tennessee
city: Dusseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf Hospital Duesseldorf
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù, IRCCS
city: Al Mathar Ash Shamali
country: Saudi Arabia
facility: King Faisal Specialist Hospital and Research Centre
Study officials:
References: