A Phase 1/2/3 Study of the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) in Subjects With Transfusion-Dependent β-Thalassemia

Plain English Summary

A Safety and Efficacy Study Evaluating CTX001 in Participants With Transfusion-Dependent β-Thalassemia is a Phase 3 clinical trial sponsored by Vertex Pharmaceuticals Incorporated studying Beta-Thalassemia, Thalassemia, Genetic Diseases, Inborn, Hematologic Diseases, Hemoglobinopathies. Tests a single dose of CRISPR-modified stem cells to treat transfusion-dependent beta-thalassemia. For patients with severe beta-thalassemia who need regular blood transfusions. Participation involves a one-time infusion of modified stem cells after a brief treatment to clear the bone marrow. Alternative treatments include regular blood transfusions and bone marrow transplants. The trial aims to enroll 59 participants.

Official Summary

This is a single-arm, open-label, multi-site, single-dose Phase 1/2/3 study in participans with transfusion-dependent β-thalassemia (TDT). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) using CTX001.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if diagnosed with beta-thalassemia and needing regular blood transfusions. Not eligible if have a matching donor or other blood disorders. Age range: 10 years and older. Good overall health and no active infections. This trial is studying Beta-Thalassemia, Thalassemia, Genetic Diseases, Inborn, Hematologic Diseases, Hemoglobinopathies, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures focus on achieving long-term transfusion independence, which would significantly improve patients' quality of life. The specific primary outcome measures are: Proportion of participants achieving transfusion independence for at least 12 consecutive months (TI12) (From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion]); Proportion of participants with engraftment (first day of 3 consecutive measurements of absolute neutrophil count [ANC] ≥500/µL on three different days) (Within 42 days after CTX001 infusion); Time to neutrophil and platelet engraftment (Days post-infusion to engraftment); Frequency and severity of collected adverse events (AEs) (Signing of informed consent through Month 24 visit); Incidence of transplant-related mortality (TRM) (Baseline (pre-transfusion) to 100 days and 1 year post-CTX001 infusion). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a critical gap by offering a potential cure for beta-thalassemia, a condition with limited treatment options. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Beta-Thalassemia, Thalassemia, Genetic Diseases, Inborn, Hematologic Diseases, Hemoglobinopathies, where improved treatment options are needed.

Investor Insight

The large market size and lack of approved treatments make this a promising investment opportunity. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you meet the eligibility criteria and if this treatment is right for you. Participation involves a one-time infusion of modified stem cells and a brief treatment to clear the bone marrow. The trial is being conducted at 14 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 59 participants

Interventions

• BIOLOGICAL: CTX001 — Administered by IV infusion following myeloablative conditioning with busulfan

Primary Outcomes

• Proportion of participants achieving transfusion independence for at least 12 consecutive months (TI12) (From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion])
• Proportion of participants with engraftment (first day of 3 consecutive measurements of absolute neutrophil count [ANC] ≥500/µL on three different days) (Within 42 days after CTX001 infusion)
• Time to neutrophil and platelet engraftment (Days post-infusion to engraftment)
• Frequency and severity of collected adverse events (AEs) (Signing of informed consent through Month 24 visit)
• Incidence of transplant-related mortality (TRM) (Baseline (pre-transfusion) to 100 days and 1 year post-CTX001 infusion)

Secondary Outcomes

• Proportion of participants achieving transfusion independence for at least 6 consecutive months (TI6) (From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion)
• Proportion of participants achieving at least 95 percent (%), 90%, 85%, 75%, and 50% reduction from baseline in annualized volume of RBC transfusions after Month 10 after CTX001 infusion (From Month 10 up to 24 months post-CTX001 infusion)
• Relative reduction from baseline in annualized volume of RBC transfusions after Month 10 after CTX001 infusion (From Month 10 up to 24 months post-CTX001 infusion)
• Duration of transfusion free in participants who have achieved TI12 (From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion)
• Proportion of alleles with intended genetic modification in peripheral blood leukocytes over time (Day 1 CTX001 infusion through Month 24 visit)

Full Eligibility Criteria

Key Inclusion Criteria:

* Diagnosis of transfusion-dependent β-thalassemia (TDT) as defined by

  1. Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Participants can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning
  2. History of at least 100 mL/kg/year or ≥10 units/year of packed RBC transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening
* Eligible for autologous stem cell transplant as per investigator's judgment

Key Exclusion Criteria:

* A willing and healthy 10/10 Human Leukocyte Antigen (HLA)-matched related donor is available per investigator's judgement
* Prior allo-HSCT
* Participants with associated α-thalassemia and \>1 alpha deletion or alpha multiplications
* Participants with sickle cell beta thalassemia variant
* Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator
* White blood cell (WBC) count \<3 × 10\^9/L or platelet count \<50 × 10\^9/L not related to hypersplenism

Other protocol defined Inclusion/Exclusion criteria may apply.

Trial Locations

• Lucile Packard Children's Hospital, Palo Alto, California, United States
• Ann & Robert Lurie Children's Hospital of Chicago, Chicago, Illinois, United States
• Columbia University Medical Center (21+ years), New York, New York, United States
• Columbia University Medical Center, New York, New York, United States
• Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
• The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers, Nashville, Tennessee, United States
• The Hospital for Sick Children, Toronto, Canada
• British Columbia Children's Hospital, Vancouver, Canada
• Universitätsklinikum Düsseldorf Hospital Duesseldorf, Düsseldorf, Germany
• Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine, Regensburg, Germany
• ...and 4 more locations

Frequently Asked Questions

Related Conditions

• Beta-thalassemia, sickle cell disease, hemoglobinopathies, genetic diseases, hematologic diseases.

More Beta-Thalassemia Trials

View all Beta-Thalassemia clinical trials