CTX001 for Sickle Cell Disease and Thalassemia

Recruiting at 7 trial locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Vertex Pharmaceuticals Incorporated

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. Please consult with the trial investigators for more details.

What data supports the idea that CTX001 for Sickle Cell Disease and Thalassemia is an effective treatment?

The available research does not provide specific data on CTX001 for Sickle Cell Disease and Thalassemia. However, it mentions other treatments like hydroxyurea, which is shown to be effective for some patients with these conditions. For example, a study found that certain genetic variants can predict how well patients respond to hydroxyurea, suggesting it can be effective for those with specific genetic markers. This implies that while CTX001's effectiveness isn't directly discussed, other treatments have shown promise based on genetic factors. ^{1 2 3 4 5}

What safety data is available for CTX001 (exa-cel) treatment in Sickle Cell Disease and Thalassemia?

The provided research does not contain specific safety data for CTX001 (exa-cel) treatment in Sickle Cell Disease and Thalassemia. The studies focus on other treatments like hydroxyurea, deferasirox, and ruxolitinib, but do not mention CTX001 or exa-cel. Therefore, no relevant safety data for CTX001 is available in the given research. ^{4 6 7 8 9}

Is the treatment CTX001 a promising treatment for Sickle Cell Disease and Thalassemia?

Yes, CTX001 is a promising treatment for Sickle Cell Disease and Thalassemia. It uses a technique called CRISPR-Cas9 gene editing to help patients produce more fetal hemoglobin, which can reduce symptoms and make them less dependent on blood transfusions. In trials, patients showed significant improvements, like increased fetal hemoglobin levels and reduced disease symptoms. ^{10 11 12 13 14}

Research Team

Eligibility Criteria

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.

Inclusion Criteria

I am considered suitable for a stem cell transplant by my doctor.

I have severe sickle cell disease and have had at least two severe pain crises per year for the last two years.

I have been diagnosed with TDT and need regular blood transfusions.

Exclusion Criteria

Participants with TDT and SCD: A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement. Prior hematopoietic stem cell transplant (HSCT). Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.

I have TDT with specific genetic changes or sickle cell β-thalassemia.

I have sickle cell disease and moyamoya syndrome that hasn't been treated.

Treatment Details

Interventions

• CTX001 (Gene Editing)

Trial Overview 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.

Participant Groups

Group I: CTX001 Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

Vertex Pharmaceuticals Incorporated

Lead Sponsor

Trials

267

Recruited

36,100+

Dr. David Altshuler

Vertex Pharmaceuticals Incorporated

Chief Medical Officer since 2020

MD, PhD

Dr. Reshma Kewalramani

Vertex Pharmaceuticals Incorporated

Chief Executive Officer since 2020

MD, trained in internal medicine and nephrology

CRISPR Therapeutics

Industry Sponsor

Trials

7

Recruited

630+

Findings from Research

Ruxolitinib therapy in 22 children with thalassemia after stem cell transplantation effectively reduced the incidence and severity of graft-versus-host disease (GVHD), with no transplant-related deaths reported.

The treatment did not negatively impact hematopoietic recovery and improved overall survival, indicating its potential as a safe and effective option for managing post-transplant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Clinical Observation with Ruxolitinib as Graft-Versus-Host Disease Prophylaxis for Children with Thalassemia after Unrelated or Haploidentical Allo-Hematopoietic Stem Cell Transplantation]. Chen, YM., Hong, XL., Lin, JZ., et al.[2022]

In a study of 29 patients with β-thalassaemia intermediate, those treated with hydroxyurea showed significant improvements in hemoglobin levels and a decrease in blood transfusion dependency, with an effective treatment rate of 85.71%.

No serious side reactions were reported in patients receiving hydroxyurea, indicating it is a safe treatment option, although long-term effects need further monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Curative Effects of Hydroxyurea on the Patients with β-thalassaemia Intermadia]. Huang, L., Yao, HX.[2018]

The study demonstrates that targeting specific mutations in thalassemia, such as IVS1-110G>A and IVS2-654C>T, using advanced gene-editing techniques (Cas9 and Cas12a/Cpf1) in hematopoietic stem cells can effectively restore normal gene function.

This approach shows high efficiency in correcting mutations and reversing abnormal splicing in blood cells, suggesting it could significantly benefit patients with transfusion-dependent β-thalassemia by potentially reducing their need for transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Editing aberrant splice sites efficiently restores β-globin expression in β-thalassemia. Xu, S., Luk, K., Yao, Q., et al.[2022]

In a study of 103 beta-thalassemia patients (83 heterozygous and 20 homozygous) compared to 117 controls, the wild-type homozygous (AA) genotype was found more frequently in beta-thalassemia patients, indicating a potential genetic predisposition.

Despite the prevalence of certain clinical manifestations like iron overload and splenomegaly in beta-thalassemia homozygotes, the FOXO3 SNP rs3800231 did not significantly influence these clinical outcomes, suggesting it may not be a key modifier of disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of FOXO3 polymorphism (rs3800231) and clinical subphenotypes of beta thalassemic individuals. Torres, FF., Bernardo, VS., Silva, DGH., et al.[2022]

Using CRISPR-Cas9 to edit the BCL11A enhancer in CD34+ cells from two patients with transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) resulted in over 80% successful gene modification without off-target effects.

Both patients showed significant clinical improvements, including high levels of fetal hemoglobin, transfusion independence, and elimination of vaso-occlusive episodes in the SCD patient, more than a year after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. Frangoul, H., Altshuler, D., Cappellini, MD., et al.[2021]

Traditional treatment for β-thalassemia major, such as allogeneic bone marrow transplantation, faces challenges like a limited number of matched donors and risks of immunological complications, prompting the need for new therapies.

Gene editing tools, including CRISPR and zinc-finger nucleases, show promise in treating β-thalassemia by enabling targeted modifications to enhance hemoglobin production and regulate gene expression, offering potential alternatives to current treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene Editing-Based Technologies for Beta-hemoglobinopathies Treatment. Rahimmanesh, I., Boshtam, M., Kouhpayeh, S., et al.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

[Clinico-biological and immunohaematological profile of patients with β-thalassemia in Tunisia: about 26 cases]. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Genomic variants in members of the Krüppel-like factor gene family are associated with disease severity and hydroxyurea treatment efficacy in β-hemoglobinopathies patients. [2021]

3. Denmark pubmed.ncbi.nlm.nih.gov

Addition of ruxolitinib in Graft-versus-Host disease prophylaxis for pediatric β-Thalassemia major patients after allogeneic stem cell transplantation: A retrospective cohort study. [2023]

4. China pubmed.ncbi.nlm.nih.gov

[The Clinical Observation with Ruxolitinib as Graft-Versus-Host Disease Prophylaxis for Children with Thalassemia after Unrelated or Haploidentical Allo-Hematopoietic Stem Cell Transplantation]. [2022]

5. China pubmed.ncbi.nlm.nih.gov

[Curative Effects of Hydroxyurea on the Patients with β-thalassaemia Intermadia]. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Drug safety in thalassemia: lessons from the present and directions for the future. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Compliance and satisfaction with deferasirox (Exjade®) compared with deferoxamine in patients with transfusion-dependent beta-thalassemia. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of hydroxyurea in patients with non-transfusion-dependent β-thalassemia: a comprehensive single-center experience. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Chronic Administration of Hydroxyurea (HU) Benefits Caucasian Patients with Sickle-Beta Thalassemia. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Editing aberrant splice sites efficiently restores β-globin expression in β-thalassemia. [2022]

11. Brazil pubmed.ncbi.nlm.nih.gov

Association of FOXO3 polymorphism (rs3800231) and clinical subphenotypes of beta thalassemic individuals. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. [2021]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Gene Editing-Based Technologies for Beta-hemoglobinopathies Treatment. [2022]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Association of Xmn1 -158 γG variant with severity and HbF levels in β-thalassemia major and sickle cell anaemia. [2021]