What side effects are associated with this type of intervention?

Common treatments for hemoglobin disorders include gene editing therapies like CRISPR-Cas9 and medications such as hydroxyurea. Gene editing therapies, while promising, can have potential side effects including off-target genetic modifications, which may lead to unintended consequences. Hydroxyurea, widely used for sickle cell disease, has been shown to be generally safe but can cause side effects such as lower total lymphocytes, CD4-positive T-cells, and memory T-cells. It may also lead to mild neutropenia, thrombocytopenia, and anemia. Long-term use of hydroxyurea has not been associated with significant adverse effects on growth or development in children.

What prior FDA approvals exist?

The FDA has approved several treatments for hemoglobin disorders, including hydroxyurea, which is widely used for sickle cell disease to reduce the frequency of painful crises and other complications. Luspatercept (REBLOZYL®) has been approved for the treatment of anemia associated with beta-thalassemia. These treatments aim to manage symptoms and improve quality of life. While CTX001 represents a novel gene-editing approach using CRISPR-Cas9 technology, it is still under investigation and has not yet received FDA approval.

What other types of research exist?

Promising alternatives to CTX001 for hemoglobin disorders include: 1) Gene editing using high-fidelity CRISPR-Cas9 variants to reduce off-target effects, 2) Lentiviral vector-based gene therapy to introduce functional copies of the β-globin gene, 3) Allogeneic hematopoietic stem cell transplantation from matched sibling donors, and 4) Novel pharmacological agents like luspatercept for improving hemoglobin levels and reducing transfusion dependency.

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Gene Editing

CTX001 for Sickle Cell Disease and Thalassemia

Phase 3

Recruiting

Research Sponsored by Vertex Pharmaceuticals Incorporated

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be younger than 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial tests a new treatment where a patient's own blood stem cells are modified to fix faulty genes. It targets patients with severe blood disorders who need frequent transfusions. The goal is to help their bodies produce healthy blood cells. Recent advances in treatment methods expand the potentially curative options for patients.

Who is the study for?

This trial is for individuals with transfusion-dependent β-thalassemia or severe sickle cell disease who are eligible for a stem cell transplant. It's not open to those with prior transplants, available matched donors, certain genetic conditions like α-thalassemia in TDT patients, or untreated moyamoya syndrome in SCD patients.

What is being tested?

The study tests CTX001, which involves editing the patient's own stem cells using CRISPR-Cas9 technology and then returning them to the body. The goal is to see if this single-dose treatment can safely improve symptoms of these blood disorders.

What are the potential side effects?

Potential side effects may include typical risks associated with stem cell transplants such as infection risk due to immune suppression during conditioning, possible infusion reactions, and complications from the gene-editing process.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: CTX001Experimental Treatment1 Intervention

CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Participants will receive a single infusion of CTX001 through a central venous catheter.

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for hemoglobin disorders include hydroxyurea, hematopoietic stem cell transplantation (HSCT), and gene therapy. Hydroxyurea works by increasing fetal hemoglobin production, which reduces the sickling of red blood cells in sickle cell disease (SCD). HSCT involves replacing the patient's defective stem cells with healthy donor cells, which can cure the disease but comes with significant risks and accessibility issues. Gene therapy, particularly using CRISPR-Cas9 as in the CTX001 trial, involves editing the patient's own hematopoietic stem cells to correct the genetic mutation causing the disorder. This approach aims to provide a long-term cure with fewer complications compared to HSCT. These mechanisms are crucial for patients as they offer potential curative options, improving quality of life and reducing disease-related complications.

Curative therapy for hemoglobinopathies: an International Society for Cell & Gene Therapy Stem Cell Engineering Committee review comparing outcomes, accessibility and cost of ex vivo stem cell gene therapy versus allogeneic hematopoietic stem cell transplantation.Highly efficient editing of the β-globin gene in patient-derived hematopoietic stem and progenitor cells to treat sickle cell disease.Hematopoietic stem cell transplantation for Gaucher disease.