Clinical Trial

Disease: Sickle Cell Disease, SCD, and Transfusion-Dependent Beta-Thalassemia, TDT, (NCT05477563)

Disease info:

Sickle cell disease is a group of disorders that affects haemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disorder have atypical hemoglobin molecules called hemoglobin S, which can distort red blood cells into a sickle or crescent shape.

The production of hemoglobin A, which is the principle type of hemoglobin in humans, is governed by 3 genes: HBA1, HBA2, and HBB. Each hemoglobin A molecule consists of two alpha and two beta chains, and mutations in either of the HBA or the HBB genes may result in abnormal hemoglobin molecules with reduced or diminished function. Sickle cell disease arises from a single point mutation in the 6th codon  of the beta-globin gene (HBB), which results in a valine instead of a glutamic acid in the hemoglobin beta-chain.

Abnormal hemoglobin ultimately leads to anemia as well as other symptoms, depending on the exact mutations present. Diseases caused by defective hemoglobin fall into a larger category of diseases known as the "haemoglobinopathies" which also include the thalassemias, a related group of diseases that are characterized by reduced or deficient rather than abnormal haemoglobin. 

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.


Sickle cell disease affects approximately 100,000 individuals in the USA and more than 3 million worldwide. Exact prevalence is unknown but annual incidence at birth of symptomatic BT is estimated at 1/100,000 worldwide.
Official title:
A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease


Name: Medical Information

Phone Number:617-341-6777



United States, New York

Columbia University Medical Center, New York, New York, United States, 10032


United States, North Carolina

Atrium Health Levine Children's Hospital, Charlotte, North Carolina, United States, 28203


United States, Tennessee

SCRI at the Children's Hospital at TriStar Centennial, Nashville, Tennessee, United States, 37203


Germany, Duesseldorf

Universitätsklinikum Düsseldorf Hospital Duesseldorf, Duesseldorf, Germany


Italy, Rome

Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy


Study start:
Aug. 2, 2022
18 participants
Gene editing method:
Type of edit:
Gene disruption
BAF Chromatin Remodeling Complex Subunit 11A (BCL11A)
Delivery method:
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Active recruiting


This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001.

Last updated: Mar. 22, 2024
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