Clinical Trial

Disease: Transfusion Dependent Beta-Thalassemia, TDT, (NCT03432364)

Disease info:

Beta thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout the body.

Hemoglobin is produced by genes that control the expression of the hemoglobin protein. Defects in these genes can produce abnormal hemoglobins and anemia, which are conditions termed "hemoglobinopathies". Abnormal hemoglobins appear in one of three basic circumstances:

Structural defects in the hemoglobin molecule. Alterations in the gene for one of the two hemoglobin subunit chains, alpha (a) or beta (b), are called mutations. Often, mutations change a single amino acid building block in the subunit. Most commonly the change is innocuous, perturbing neither the structure nor function of the hemoglobin molecule. Occasionally, alteration of a single amino acid dramatically disturbs the behavior of the hemoglobin molecule and produces a disease state. Sickle hemoglobin exemplifies this phenomenon.

Diminished production of one of the two subunits of the hemoglobin molecule. Mutations that produce this condition are termed "thalassemias." Equal numbers of hemoglobin alpha and beta chains are necessary for normal function. Hemoglobin chain imbalance damages and destroys red cells thereby producing anemia. Although there is a dearth of the affected hemoglobin subunit, with most thalassemias the few subunits synthesized are structurally normal.

Abnormal associations of otherwise normal subunits. A single subunit of the alpha chain (from the a-globin locus) and a single subunit from the b-globin locus combine to produce a normal hemoglobin dimer. With severe a-thalassemia, the b-globin subunits begin to associate into groups of four (tetramers) due to the paucity of potential a-chain partners. These tetramers of b-globin subunits are functionally inactive and do not transport oxygen. No comparable tetramers of alpha globin subunits form with severe beta-thalassemia. Alpha subunits are rapidly degraded in the absence of a partner from the beta-globin gene cluster (gamma, delta, beta globin subunits).

In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body. People with beta thalassemia are at an increased risk of developing abnormal blood clots.

Beta thalassemia is a fairly common blood disorder worldwide. Thousands of infants with beta thalassemia are born each year. Beta thalassemia occurs most frequently in people from Mediterranean countries, North Africa, the Middle East, India, Central Asia
Official 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)

United States, California

University of California, Los Angeles, Los Angeles, California, United States, 90095-1678

UCSF Benioff Children's Hospital Oakland, Oakland, California, United States, 94609


United States, Georgia

Children's Healthcare of Atlanta, Atlanta, Georgia, United States, 30322


United States, Massachusetts

Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, United States, 02116


United States, Minnesota

University of Minnesota, Minneapolis, Minnesota, United States, 55455


United States, Pennsylvania

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States, 19104

Study start:
Mar. 29, 2018
5 participants
Gene editing method:
ZFN-Zinc Finger Nucleases
Type of edit:
Gene enhancement
BAF chromatin remodelling complex subunit (BCL11A)
Delivery method:
Electroporation and adeno-associated virus (AAV) - Ex-vivo
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Completed


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.

ST-400 Investigational product is composed of autologous CD34+ hematopoietic stem/progenitor cells that are genetically modified ex vivo at the erythroid-specific enhancer of the BCL11A gene

Intervention: Genetic: ST-400 Investigational product

Last updated: Jun. 11, 2023
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