Evaluating a single dose of CTX001 for treating transfusion-dependent beta-thalassemia and severe sickle cell disease

A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease

This study is testing a single dose of a new treatment called CTX001 to see if it can help people with transfusion-dependent beta-thalassemia or severe sickle cell disease feel better.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 26 (estimated)
• Ages: 12 Years to 35 Years
• Sex: All
• Sponsor: Vertex Pharmaceuticals Incorporated (Industry-sponsored)
• Locations: 6 sites (New York, New York and 5 other locations)
• Trial ID: NCT05477563 on ClinicalTrials.gov

What this trial studies

This clinical trial is an open-label, single-dose study aimed at assessing the safety and efficacy of CTX001, which involves the use of CRISPR-Cas9 modified human hematopoietic stem and progenitor cells. Participants include individuals with transfusion-dependent beta-thalassemia or severe sickle cell disease who are eligible for autologous stem cell transplant. The study will monitor the participants for improvements in their condition and any potential side effects following treatment.

Who should consider this trial

Good fit: Ideal candidates are individuals diagnosed with transfusion-dependent beta-thalassemia or severe sickle cell disease who meet specific eligibility criteria for autologous stem cell transplant.

Not a fit: Patients who are not eligible for autologous stem cell transplant or do not have the specified diagnoses may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce or eliminate the need for blood transfusions in patients with beta-thalassemia and improve the quality of life for those with severe sickle cell disease.

How similar studies have performed: Other studies utilizing CRISPR technology for genetic diseases have shown promising results, indicating potential for success in this novel approach.

Eligibility criteria

Key Inclusion Criteria:

* Participants with TDT and SCD:
* Eligible for autologous stem cell transplant as per investigator's judgment.
* Participants with TDT:
* Diagnosis of TDT as defined by:
* 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
* History of at least 100 milliliter (mL)/kilograms (kg)/year or 10 units/year of packed red blood cells (RBC) transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening
* Participants with SCD:
* Diagnosis of severe SCD as defined by:
* Documented SCD genotypes
* History of at least two severe VOCs events per year for the previous two years prior to enrollment

Key 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
* Participants with TDT:
* Participants with associated α-thalassemia and \>1 alpha deletion, or alpha multiplications
* Participants with sickle cell β-thalassemia variant
* Participants with SCD:
* History of untreated moyamoya syndrome or presence of moyamoya syndrome at screening

Other protocol defined Inclusion/Exclusion criteria may apply.

Where this trial is running

New York, New York and 5 other locations

• New York Presbyterian Hospital - Morgan Stanley Children's Hospital — New York, New York, United States (Recruiting)
• Levine Children's Hospital - Hematology — Charlotte, North Carolina, United States (Recruiting)
• TriStar Medical Group Children's Specialists - Pediatric Oncology — Nashville, Tennessee, United States (Recruiting)
• University Hospital Dusseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology — Düsseldorf, Germany (Recruiting)
• IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica — Rome, Italy (Recruiting)
• King Faisal Specialist Hospital & Research Centre - Riyadh - Hematology — Al Mathar Ash Shamali, Saudi Arabia (Recruiting)

Study contacts

• Study coordinator: Medical Information

Conditions Beta-Thalassemia; Thalassemia; Hematologic Diseases; Genetic Diseases, Inborn; Hemoglobinopathies; Sickle Cell Disease; Sickle Cell Anemia