This is a single-dose, open-label study in pediatric participants with severe SCD and hydroxyurea (HU) failure or intolerance. The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (CTX001).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Administered by intravenous infusion following myeloablative conditioning with busulfan.
Levine Children's Hospital - Hematology
Charlotte, North Carolina, United States
The Children's Hospital of Philadelphia - Hematology
Philadelphia, Pennsylvania, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
TriStar Medical Group Children's Specialists - Pediatric Oncology
Nashville, Tennessee, United States
University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology
Düsseldorf, Germany
IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica
Rome, Italy
St.Mary's Hospital - Haematology Dept
London, United Kingdom
Proportion of Participants who do not Have any Severe Vaso-occlusive Crises (VOCs) for at Least 12 Consecutive Months (VF12)
Time frame: Up to 24 Months After CTX001 Infusion
Proportion of Participants Free from Inpatient Hospitalization for Severe VOCs for at Least 12 Months (HF12)
Time frame: Up to 24 Months After CTX001 Infusion
Relative Reduction in Annualized Rate of Severe VOCs
Time frame: From Baseline up to 24 Months After CTX001 Infusion
Duration of Severe VOC Free in Participants who Have Achieved VF12
Time frame: Up to 24 Months After CTX001 Infusion
Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs
Time frame: From Baseline up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained Fetal Hemoglobin (HbF) ≥20 Percent (%) for at Least 3 Months
Time frame: Up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained HbF ≥20% for at Least 6 Months
Time frame: Up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained HbF ≥20% for at Least 12 Months
Time frame: Up to 24 Months After CTX001 Infusion
Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time
Time frame: Up to 24 Months After CTX001 Infusion
Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time
Time frame: Up to 24 Months After CTX001 Infusion
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Signing of Informed Consent up to 24 Months After CTX001 Infusion
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
Time to Engraftment
Time frame: Up to 24 Months After CTX001 Infusion
Incidence of Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion
Time frame: Within 100 Days After CTX001 infusion
Incidence of TRM Within 12 Months After CTX001 Infusion
Time frame: Within 12 Months After Infusion
Incidence of All-cause Mortality
Time frame: From Signing of Informed Consent up to 24 Months After CTX001 Infusion
Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs
Time frame: From Baseline up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained HbF ≥30% for at Least 3 Months
Time frame: Up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained HbF ≥30% for at Least 6 Months
Time frame: Up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained HbF ≥30% for at Least 12 Months
Time frame: Up to 24 Months After CTX001 Infusion
Time for Participants to Reach HbF ≥20%
Time frame: Up to 24 Months After CTX001 Infusion
Time for Participants to Reach HbF ≥30%
Time frame: Up to 24 Months After CTX001 Infusion
Relative Reduction from Baseline in Annualized Volume and Episodes of RBC Transfusions for SCD-related indications starting after Month 12 post-CTX001 infusion
Time frame: Up to 24 Months After CTX001 Infusion
HbF Concentrations Over Time
Time frame: Up to 24 Months After CTX001 Infusion
Hemoglobin (Hb) Concentrations Over Time
Time frame: Up to 24 Months After CTX001 Infusion
Change in Reticulocyte Count Over Time
Time frame: From Baseline up to 24 Months After CTX001 Infusion
Change in Indirect Bilirubin Over Time
Time frame: From Baseline up to 24 Months After CTX001 Infusion
Change in Haptoglobin Over Time
Time frame: From Baseline up to 24 Months After CTX001 Infusion
Proportion of Participants with Detectable Haptoglobin Over Time
Time frame: Up to 24 Months After CTX001 Infusion
Change in Lactate Dehydrogenase (LDH) Over Time
Time frame: From Baseline (Pre-infusion) up to 24 Months After CTX001 Infusion
Proportion of Participants with Normalized LDH Over Time
Time frame: Up to 24 Months After CTX001 Infusion
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