Transfusion-dependent ß-thalassemia (TDT) and severe sickle cell disease (SCD) MedDRA version: 21.0 Level: PT Classification code 10040641 Term: Sickle cell anaemia System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.1 Level: LLT Classification code 10054660 Term: Thalassemia beta System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Exagamglogene autotemcel (Exa-cel)
Product Code: CTX001
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem
Sponsors
Vertex Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess HbF levels over time, after a single dose of autologous CRISPR/Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (CTX001) in adolescent and adult subjects with either Transfusion-dependent 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 adult subjects with either TDT or severe SCD • Assess the effects of infusion of CTX001 on disease-specific events and clinical status • Quantify gene editing efficiency;Primary end point(s): HbF and Hb levels over time. The evaluation will start 60 days after last RBC transfusion for post-transplant support or disease management.;Timepoint(s) of evaluation of this end point: Up to 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): TDT or SCD: • Safety and tolerability of CTX001 based on adverse events (AEs), clinical laboratory values, neutrophil engraftment, platelet engraftment, transplant-related mortality (TRM), and all-cause mortality. • Relative reduction from baseline in annualized volume of RBC • Proportion of alleles with intended genetic modification present in peripheral blood over time • Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time TDT only: • Duration transfusion free SCD only: • Relative reduction from baseline in annualized rate of severe VOCs up to 12 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management. • Relative reduction from baseline in rate of inpatient hospitalizations for severe VOCs up to 12 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management. • Relative change from baseline in annualized duration of hospitalization for severe VOCs up to 12 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management • Relative reduction from baseline in markers of hemolysis up to 12 months after CTX001 infusion.;Timepoint(s) of evaluation of this end point: Up to 12 months | — |
Countries
Germany, Italy, Saudi Arabia, United States
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed