CASPER: A Study to Evaluate the Safety and Efficacy of CRISPR Cas9 Gene Editing in Patients with Severe Sickle Cell Disease

A Phase I/II 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

Categories:

Phase I/II

Hematological Disorders

Diseases Treated:

Sickle Cell Disease

Eligibility Overview:

  • 18 to 35 years old (Ages 18 to 25 at St. Jude)
  • Diagnosis of severe sickle cell disease (SCD)
  1. 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 a matched donor and carries the risk of graft-versus-host disease. Current 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 through editing of a non-coding region in the BCL11A gene. BCL11A is a transcriptional silencer of γ-globin gene expression and, hence, acts as an “off switch” for HbF. Turning off BCL11A switches HbF back on.

    St. Jude is one of several sites for the CASPER trial, which is sponsored by CRISPR Therapeutics AG and 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:

    • 18 to 35 years old (Ages 18 to 25 at St. Jude)
    • Diagnosis of severe sickle cell disease
    • Documented βSS genotype
    • Eligible for autologous stem cell transplant

    Exclusion Criteria include:

    • An available 10/10 human leukocyte antigen (HLA)-matched related donor.
    • Prior HSCT
    • 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.

  2. About this study

    This is a clinical trial to learn about the safety and effects of CTX001 in patients with severe sickle cell disease (SCD). CTX001 is considered investigational, which means it has not been approved by the U.S. Food and Drug Administration (FDA). The goal of this study is to see if a single dose of CTX001 allows your body to increase the amount of a certain kind of hemoglobin called hemoglobin F (HbF) while decreasing the effects of SCD. Hemoglobin is a protein in red blood cells that carries oxygen to the body.

    If you participate in this study, we will collect bone marrow cells (stem cells) from you and send them to a laboratory. Next, we will edit (change) the DNA in a specific gene in your cells to create the study product, CTX001. The technology we use to edit the DNA in the cell is called CRISPR/Cas9. It cuts the DNA like scissors. The blood stem cell then repairs the cut DNA using its natural repair tools. We hope this repair will help your body produce more hemoglobin F.

    After we change your cells using CRISPR/Cas9, we will return them to you through your veins. This procedure is called an autologous bone marrow transplant and takes place in the hospital. You will take medicine to remove your own bone marrow cells and create “room” for the incoming edited cells. We will then infuse the modified cells into your vein.

    Purpose of this clinical trial

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

    Eligibility overview

    • 18 to 35 years old (Ages 18 to 25 at St. Jude)
    • Diagnosis of severe sickle cell disease

     

  3. CASPER Quick View
    Sponsors CRISPR Therapeutics AG and Vertex Pharmaceuticals
    ClinicalTrials.gov Identifier NCT03745287
    Trial Sart Date November 2018
    Estimated Enrollment 45
    Study Type Interventional
    Study Phase Phase I/II
    Conditions Sickle cell disease
    Ages 18 to 35 years old (Ages 18 to 25 at St. Jude)
    Site Principal Investigator Akshay Sharma, MD
    Study Sites St. Jude Children’s Research Hospital and collaborating sites in and outside the U.S.
    For a consultation or to discuss CASPER

    St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

     

Contact:

Akshay Sharma, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105 USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

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