Disease: Sickle Cell Disease, Haematological Diseases, Haemoglobinopathies, (NCT03745287)

Disease info:

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

Haemoglobin 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 "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).

Sickle cell disease is the most common inherited blood disorder in the United States, affecting 70,000 to 80,000 Americans. The disease is estimated to occur in 1 in 500 African Americans and 1 in 1,000 to 1,400 Hispanic Americans.
Official title:
A Phase 1/2 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Severe Sickle Cell Disease

No information


United States, California

United States, Illinois

United States, New York

United States, Pennsylvania

United States, Tennessee

United States, Texas

Belgium, Brussels

Canada, Toronto

Germany, Regensburg

Italy, Rome

United Kingdom, London


Study start:
Nov. 27, 2018
45 participants
Gene editing method:
Type of edit:
Gene disruption
BAF Chromatin Remodeling Complex Subunit 11A (BCL11A)
Delivery method:
Electroporation - Ex-vivo
BCL11A is a transcription factor and key component of haemoglobin (Hb) switch that regulates the repression of g-globin chain production occurring early in the post-natal period, leading to the production of adult HbA. Suppression of BCL11A is associated with increases in fetal Hb (HbF). In both transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD), HbF upregulation may reduce or eliminate the need for transfusion therapy and, in SCD, may reduce vaso-occlusive crises (VOCs).
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Active recruiting


This is a single-arm, open-label, multi-site, single-dose Phase 1/2 study in subjects 18 to 35 years of age with severe sickle cell disease (SCD). 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)
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