A Study to Assess the Safety, Tolerability, and Efficacy of ST-400 for Treatment of Transfusion-Dependent Beta-thalassemia (TDT)

Sangamo Therapeutics5 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 Years

Medical Language ↔ Plain English

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

Locations (6)

University of California, Los Angeles

Los Angeles, California, United States

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Dana-Farber Boston Children's Cancer and Blood Disorders Center

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 Weeks After the ST-400 Infusion

Safety and tolerability assessed by number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 weeks after the ST-400 infusion

Time frame: Up to 156 weeks after the ST-400 infusion

Secondary Outcomes

Clinical Laboratory Measurement of Hemoglobin (Hb) Fractions (A and F in g/dL)

Change from baseline clinical laboratory measurement of Hb fractions (A and F in g/dL) \[Time Frame: Up to 156 weeks after ST-400 infusion\]

Time frame: Baseline, Weeks 26, 52, and 156 after ST-400 infusion

Clinical Laboratory Measurements of Percent (%) HbF

Change from baseline percent (%) HbF \[Time Frame: Up to 156 weeks after ST-400 infusion\]

Time frame: Baseline, Weeks 26, 52, and 156 after ST-400 infusion

Annualized Frequency of Packed RBC Transfusions

Calculation of annualized frequency and volume of packed red blood cell (PRBC) transfusions after ST-400 infusion transfusion support in the 2 years prior to screening

Time frame: From Baseline (2 years prior to screening/consent), to ST-400 Infusion (Day 0), after hematopoietic reconstitution and up to 156 weeks (post ST-400 infusion)

Annualized Volume (mL) of Packed RBC Transfusions

Historical baseline defined as transfusion support in the 2 years prior to screening.