Clinical trial NCT05329649: Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Severe Sickle Cell Disease (SCD)
Official title: A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Severe Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Sickle Cell Disease
Hydroxyurea Failure
Hydroxyurea Intolerance
Hemoglobinopathies
Hematological Diseases
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
Collaborators: name: CRISPR Therapeutics
First posted: 2022-04-15
Enrollment: 15
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Key Inclusion Criteria:

* 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
* Hydroxyurea (HU) failure unless HU intolerant
* Eligible for autologous stem cell transplant as per investigators judgment

Key Exclusion Criteria:

* A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor
* Prior hematopoietic stem cell transplant (HSCT).
* Clinically significant and active bacterial, viral, fungal, or parasitic infection

Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Proportion of Participants who do not Have any Severe Vaso-occlusive Crises (VOCs) for at Least 12 Consecutive Months (VF12)
timeFrame: Up to 24 Months After CTX001 Infusion
Secondary outcomes:
measure: Proportion of Participants Free from Inpatient Hospitalization for Severe VOCs for at Least 12 Months (HF12)
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Relative Reduction in Annualized Rate of Severe VOCs
timeFrame: From Baseline up to 24 Months After CTX001 Infusion
measure: Duration of Severe VOC Free in Participants who Have Achieved VF12
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs
timeFrame: From Baseline up to 24 Months After CTX001 Infusion
measure: Proportion of Participants With Sustained Fetal Hemoglobin (HbF) ≥20 Percent (%) for at Least 3 Months
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Proportion of Participants With Sustained HbF ≥20% for at Least 6 Months
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Proportion of Participants With Sustained HbF ≥20% for at Least 12 Months
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Signing of Informed Consent up to 24 Months After CTX001 Infusion
measure: 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: Time to Engraftment
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Incidence of Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion
timeFrame: Within 100 Days After CTX001 infusion
measure: Incidence of TRM Within 12 Months After CTX001 Infusion
timeFrame: Within 12 Months After Infusion
measure: Incidence of All-cause Mortality
timeFrame: From Signing of Informed Consent up to 24 Months After CTX001 Infusion
measure: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs
timeFrame: From Baseline up to 24 Months After CTX001 Infusion
measure: Proportion of Participants With Sustained HbF ≥30% for at Least 3 Months
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Proportion of Participants With Sustained HbF ≥30% for at Least 6 Months
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Proportion of Participants With Sustained HbF ≥30% for at Least 12 Months
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Time for Participants to Reach HbF ≥20%
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Time for Participants to Reach HbF ≥30%
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Relative Reduction from Baseline in Annualized Volume and Episodes of RBC Transfusions for SCD-related indications starting after Month 12 post-CTX001 infusion
timeFrame: Up to 24 Months After CTX001 Infusion
measure: HbF Concentrations Over Time
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Hemoglobin (Hb) Concentrations Over Time
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Change in Reticulocyte Count Over Time
timeFrame: From Baseline up to 24 Months After CTX001 Infusion
measure: Change in Indirect Bilirubin Over Time
timeFrame: From Baseline up to 24 Months After CTX001 Infusion
measure: Change in Haptoglobin Over Time
timeFrame: From Baseline up to 24 Months After CTX001 Infusion
measure: Proportion of Participants with Detectable Haptoglobin Over Time
timeFrame: Up to 24 Months After CTX001 Infusion
measure: Change in Lactate Dehydrogenase (LDH) Over Time
timeFrame: From Baseline (Pre-infusion) up to 24 Months After CTX001 Infusion
measure: Proportion of Participants with Normalized LDH Over Time
timeFrame: Up to 24 Months After CTX001 Infusion
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: Atrium Health Levine Children's Hospital
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers
state: Tennessee
city: Dusseldorf
country: Germany
facility: University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology
city: Rome
country: Italy
facility: Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS
city: London
country: United Kingdom
facility: St Mary's Hospital
Study officials:
References: