CASPERKID: Study of CTX001 in Children with Severe Sickle Cell Disease

This study will use CRISPR-Cas9 gene editing to restore fetal hemoglobin (HbF) production in patients with severe sickle cell disease (SCD) and ameliorate clinical symptoms.

Allogeneic hematopoietic stem cell transplant is the only known cure for SCD. However, the procedure is only available to about 20% of patients who have matched donors and carries the risk of graft-versus-host disease. Approved therapies to prevent SCD complications include hydroxyurea and L-glutamine oral powder, but patients can still have breakthrough vaso-occlusive crises.

The CRISPR-Cas9 editing-based therapeutic approach aims to restore HbF production by editing a non-coding region in the BCL11A gene. BCL11A is a transcriptional silencer of γ-globin gene expression and acts as an “off switch” for HbF. Turning off BCL11A switches HbF back on.

St. Jude is one of several sites for the CASPERKID trial sponsored by Vertex Pharmaceuticals.

Primary Objective

To evaluate the safety and efficacy of a single dose of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (CTX001) in subjects with severe sickle cell disease

Eligibility Criteria

Inclusion criteria include:

• 2–11 years old (inclusive)
• Diagnosis of severe sickle cell disease
• Documented βS/βS βS/β0, or βS/β+ genotype
• Eligible for autologous stem cell transplant

Exclusion criteria include:

• An available 10/10 human leukocyte antigen (HLA)-matched related donor.
• Prior hematopoietic stem cell transplant
• Clinically significant and active bacterial, viral, fungal, or parasitic infection

Study Sites

St. Jude Children’s Research Hospital, Memphis, Tennessee
Collaborating sites in and outside the U.S.

About this study

This is a clinical trial to learn about the safety and possible side effects of CTX001 in children with severe sickle cell disease (SCD).

CTX001 is investigational. That means the U.S. Food and Drug Administration has not yet approved it. We want to see if a single dose of CTX001 allows your child’s body to:

• Increase the amount of a type of hemoglobin called hemoglobin F. Hemoglobin is a protein in red blood cells that delivers oxygen to the body’s cells.
• Decrease the effects of SCD

Main steps of the study:

1. We collect bone marrow cells (stem cells) from your child.
   
   
2. We send those cells to a lab. We will change (edit) the DNA of a specific gene in your child’s cells in the lab to create the study product (CTX001). The technology we use to edit the DNA is called CRISPR/Cas9. It cuts the DNA like scissors. The blood stem cells repair the cut DNA using their natural repair tools. We hope this repair will help your child’s body make more hemoglobin F.
   
   
3. Your child will get an autologous bone marrow transplant using their changed cells. This transplant takes place in the hospital. Your child will take medicine to remove their bone marrow cells and create “room” for the edited cells. We will give the modified cells into your child’s vein with an IV.
   
   
4. We hope that once the changed cells are in the body, the red blood cells will not sickle or cause complications of sickle cell disease..

Purpose of this clinical trial

The main goal of this study is to see if a single dose of CTX001 allows your child’s body to increase the amount of hemoglobin F while reducing the painful effects of sickle cell disease.

Eligibility overview

• 2–11 years old
• Diagnosis of severe sickle cell disease