Clinical Trial

Disease: Beta-Thalassemia, BT, (NCT03655678)

Disease info:

Beta-thalassemia is a group of blood disorders characterised by a reduction in the production of haemoglobin. Haemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout the body.

Haemoglobin is encoded by genes that encode the building blocks of the haemoglobin protein. Mutations in these genes can produce abnormal haemoglobins leading to a family of conditions termed "haemoglobinopathies". Abnormal haemoglobin appears in one of three basic circumstances:

  1. Structural defects in the haemoglobin molecule. Alterations in the gene for one of the two haemoglobin 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 haemoglobin molecule. Occasionally, alteration of a single amino acid dramatically disturbs the behaviour of the haemoglobin molecule and produces a disease state. Sickle haemoglobin exemplifies this phenomenon.
  2. Diminished production of one of the two subunits of the haemoglobin molecule. Mutations that produce this condition are termed "thalassemias." Equal numbers of haemoglobin alpha and beta chains are necessary for normal function. Haemoglobin chain imbalance damages and destroys red cells thereby producing anaemia. Although there is a dearth of the affected haemoglobin subunit, with most thalassemias the few subunits synthesised are structurally normal.
  3. 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 haemoglobin 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 individuals suffering from beta-thalassemia, low levels of haemoglobin 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 classified into two types depending on symptom severity. Transfusion-dependent thalassemia, also known as thalassemia major, is the more severe, while thalassemia intermedia is less severe-

Frequency:
Annually, approximately 1 in 100,000 cases are diagnosed worldwide. Beta-thalassaemia occurs most frequently in people from Mediterranean countries, North Africa, the Middle East, India, China and South East Asia.
Official title:
A Phase 1/2/3 Study of the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) in Subjects With Transfusion-Dependent β-Thalassemia
Who:
Locations:

United States, California

Stanford University, Stanford, California, United States, 94305

 

United States, Illinois

Ann & Robert Lurie Children's Hospital of Chicago, Chicago, Illinois, United States, 60611

 

United States, New York

Columbia University, Manhattan, New York, United States, 10027

 

United States, Tennessee

The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers, Nashville, Tennessee, United States, 37203

 

Canada

Hospital for Sick Children, Toronto, Canada

BC Children's Hospital, Vancouver, Canada

 

Germany

University Hospital Duesseldorf, Düsseldorf, Germany

University Hospital Regensburg, Regensburg, Germany

University Hospital Tübingen, Tuebingen, Germany

 

Italy

Bambino Gesu, Rome, Italy

 

United Kingdom

Imperial College Healthcare, London, United Kingdom

University College London Hospitals NHS Foundation Trust, London, United Kingdom

 

Study start:
Sep. 14, 2018
Enrollment:
45 participants
Gene editing method:
CRISPR-Cas9
Type of edit:
Gene disruption
Gene:
BAF Chromatin Remodeling Complex Subunit 11A (BCL11A)
Delivery method:
Electroporation - Ex-vivo
IndicatorIndicator
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Active not recruiting

Description

This is a single-arm, open-label, multi-site, single-dose Phase 1/2 study in up to 12 subjects 18 to 35 years of age with transfusion-dependent β-thalassemia (TDT). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 Modified CD34+ Human Haematopoietic Stem and Progenitor Cells (hHSPCs) using CTX001.

Last updated: Dec. 28, 2023
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