Disease: Thalassemia Genetic Diseases, Inborn Haematologic Diseases Haemoglobinopathies, (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 produced by genes that control the expression of the haemoglobin protein. Defects in these genes can produce abnormal haemoglobins and anemia, which are conditions termed "haemoglobinopathies". Abnormal haemoglobins appear in one of three basic circumstances:

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 behavior of the haemoglobin molecule and produces a disease state. Sickle haemoglobin exemplifies this phenomenon.

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 anemia. Although there is a dearth of the affected haemoglobin 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 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.

Frequency:
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 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:

No information

Locations:

United States, California

United States, New York

United States, Tennessee

Canada, Toronto

Canada, Vancouver

Germany, Regensburg

Germany, Tuebingen

Italy, Rome

United Kingdom, London

 

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 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: Apr. 6, 2021
Source: US National Institutes of Health (NIH)
clinicaltrials.gov
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