A study to learn about the safety and efficacy of CTX001 (the study drug product) to treat beta-thalassemia and severe sickle cell disease in patients
- Conditions
- Transfusion-dependent ß-thalassemia (TDT) and severe sickle cell disease (SCD)MedDRA version: 21.0Level: PTClassification code 10040641Term: Sickle cell anaemiaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersMedDRA version: 20.1Level: LLTClassification code 10054660Term: Thalassemia betaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2021-006390-37-DE
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 26
Subjects with TDT:
•Subjects 12 to 35 years of age, inclusive, on the date of informed consent
•Eligible for autologous stem cell transplant as per investigator’s judgement
•Diagnosis of transfusion-dependent ß-thalassemia (TDT) as defined by:
•Documented homozygous ß-thalassemia or compound heterozygous ß-thalassemia including ß-thalassemia/hemoglobin E (HbE). Subjects can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning.
•A history of at least 100mL/kg/year or 10 units/year of packed RBC transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening
Subjects with SCD:
•Subjects 12 to 35 years of age, inclusive, on the date of informed consent
•Documented ßS/ßS, ßS/ß0, or ßS/ß+, subjects can be enrolled based on historical genotype results, but confirmation of genotype is required before busulfan conditioning
•Eligible for autologous stem cell transplant as per investigator’s judgment
•Subjects with severe SCD. Severe SCD defined aby the occurrence of at least 2 of the following events per year during the 2-year period before screening, while receiving appropriate supportive care (e.g. pain management plan, HU):
•Acute pain events that require a visit to a medical facility and administration of pain medications (opioids or intravenous [IV] non-steroidal anti-inflammatory drugs [NSAIDs]) or RBC transfusions
•Acute chest syndrome, as indicated by the presence of a new pulmonary infiltrate associated with pneumonia-like symptoms, pain, or fever
•Priapism lasting >2 hours and requiring a visit to a medical facility
•Splenic sequestration, as defined by an enlarged spleen, left upper quadrant pain, and an acute decrease in hemoglobin concentration of =2 g/dL.
Other protocol defined inclusion criteria may apply
Are the trial subjects under 18? yes
Number of subjects for this age range: 11
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Subjects with TDT:
•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).
•Subjects with associated a-thalassemia and >1 alpha deletion, or alpha multiplications.
•Subjects with sickle cell ß-thalassemia variant.
•Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
•White blood cell (WBC) count <3 × 109/L or platelet count <50 × 109/L not related to hypersplenism per investigator judgment.
Subjects with 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.
Other protocol defined exclusion criteria may apply
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess HbF levels over time, after a single dose of autologous CRISPR/Cas9<br>modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs)<br>(CTX001) in adolescent and adult subjects with either Transfusion-dependent<br>ß-Thalassemia (TDT) or severe sickle cell disease (SCD);Secondary Objective: • To evaluate efficacy and safety of a single dose of CTX001 in adolescent and<br>adult subjects with either TDT or severe SCD<br>• Assess the effects of infusion of CTX001 on disease-specific events and<br>clinical status<br>• Quantify gene editing efficiency;Primary end point(s): HbF and Hb levels over time. The evaluation will start 60 days after last RBC<br>transfusion for post-transplant support or disease management.;Timepoint(s) of evaluation of this end point: Up to 12 months
- Secondary Outcome Measures
Name Time Method