a study to assess the safety, tolerability, and efficacy of st-400 for treatment of transfusion-dependent beta-thalassemia (tdt)

Conditions: Transfusion Dependent Beta-thalassemia

Summary: this is a single-arm, multi-site, single-dose, phase 1/2 study to assess st-400 in 6 subjects with transfusion-dependent β-thalassemia (tdt) who are ≥18 and ≤40 years of age. st-400 is a type of investigational therapy that consists of gene edited cells. st-400 is composed of the patient's own blood stem cells which are genetically modified in the laboratory using sangamo's zinc finger nuclease (zfn) technology to disrupt a precise and specific sequence of the enhancer of the bcl11a gene (which normally suppresses fetal hemoglobin production in erythrocytes). this process is intended to boost fetal hemoglobin (hbf), which can substitute for reduced or absent adult (defective) hemoglobin. st-400 is then infused back into the patient after receiving conditioning chemotherapy to make room for the new cells in the bone marrow, with the aim of producing new erythrocytes with increased amounts of hbf. the primary objective is to understand safety and tolerability of st-400, and secondary objectives are to assess the effects on hbf levels and transfusion requirements.

once consented, study participants will progress through the following stages: * screening: in-person visit at the study site to confirm eligibility for proceeding * collection: autologous (self) blood stem cells are harvested at the study site, also known as apheresis * manufacturing of st-400: no study participant activities expected * infusion: conditioning chemotherapy, followed by infusion of st-400, occurs at the study site * follow-up: follow up at the study site to monitor for safety and effectiveness of the study

Eligibility criteria:
inclusion criteria: 1. informed consent 2. clinical diagnosis of tdt with ≥ 8 documented rbc transfusion events per year on an annualized basis in the 2-years prior to screening 3. confirmed beta-thalassemia diagnosis by molecular genetic testing 4. clinically stable and eligible to receive conditioning chemotherapy 5. able and willing to use an effective method of contraception from the signing of the informed consent and for one year following st-400 infusion. exclusion criteria: 1. previous history of autologous or allogeneic blood stem cell transplantation or solid organ transplantation 2. pregnant or breastfeeding female 3. medical contraindication to mobilization, apheresis, or conditioning 4. significant liver, lung, heart, or kidney dysfunction 5. diagnosis of hiv or evidence of active hbv or hcv 6. history of significant bleeding disorder or uncontrolled seizures 7. history of active malignancy in past 5 years (non-melanoma skin cancer or cervical cancer in situ permitted) any history of hematologic malignancy, or family history of cancer predisposition syndrome without negative testing result in the study candidate. 8. currently participating in another clinical trial using an investigational study medication, or recent participation in such a trial 9. previous treatment with gene therapy

Keywords: beta thalassemia beta-thalassemia thalassemia major cooley's anemia zfn mediated genome editing zinc finger nuclease