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

Status:	Recruiting
Conditions:	Hematology
Therapuetic Areas:	Hematology
Healthy:	No
Age Range:	18 - 40
Updated:	2/6/2019
Start Date:	March 29, 2018
End Date:	December 2022
Contact:	Medical Monitor
Email:	clinicaltrials@sangamo.com
Phone:	510-307-7266

A Phase 1/2, Open-label, Single-arm Study to Assess the Safety, Tolerability, and Efficacy of ST-400 Autologous Hematopoietic Stem Cell Transplant for Treatment of Transfusion-Dependent Beta-thalassemia (TDT)

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

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

We found this trial at

sites

University of California at Los Angeles

Los Angeles, California 90095

310-825-4321