Skip to main content
OpenTrials
Completed

NCT Number: NCT03432364

A Study to Assess the Safety, Tolerability, and Efficacy of ST-400 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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Transfusion Dependent Beta-thalassemia Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Thalassemia beta-Thalassemia

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University of California, Los Angeles, Los Angeles, California, United States

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Informed Consent
  • Clinical diagnosis of TDT with ≥ 8 documented RBC transfusion events per year on an annualized basis in the 2-years prior to screening
  • Confirmed beta-thalassemia diagnosis by molecular genetic testing
  • Clinically stable and eligible to receive conditioning chemotherapy
  • 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

  • Previous history of autologous or allogeneic blood stem cell transplantation or solid organ transplantation
  • Pregnant or breastfeeding female
  • Medical contraindication to mobilization, apheresis, or conditioning
  • Significant liver, lung, heart, or kidney dysfunction
  • Diagnosis of HIV or evidence of active HBV or HCV
  • History of significant bleeding disorder or uncontrolled seizures
  • 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.
  • Currently participating in another clinical trial using an investigational study medication, or recent participation in such a trial
  • Previous treatment with gene therapy

Treatment and study plan

ST-400 Investigational product

Genetic

Single dose of ST-400 following chemotherapy conditioning with busulfan

Primary outcomes

  1. 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

    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

Secondary outcomes

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

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

    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]

  2. Clinical Laboratory Measurements of Percent (%) HbF

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

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

  3. Annualized Frequency of Packed RBC Transfusions

    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)

    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

  4. Annualized Volume (mL) of Packed RBC Transfusions

    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)

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

Sponsors and collaborators

Lead sponsor

Sangamo Therapeutics

Industry

Registry information

Official study title

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)

Important dates

Study start
2018
Primary completion
2022
Study completion
2022
First posted
Feb 14, 2018
Registry last updated
Dec 14, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.