RecruitingPhase 3NCT05477563

Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-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


Sponsor

Vertex Pharmaceuticals Incorporated

Enrollment

26 participants

Start Date

Aug 2, 2022

Study Type

INTERVENTIONAL

Conditions

Summary

This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001.


Eligibility

Min Age: 12 YearsMax Age: 35 Years

Inclusion Criteria10

  • 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

Exclusion Criteria9

  • 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

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Interventions

BIOLOGICALCTX001

Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan


Locations(6)

New York Presbyterian Hospital - Morgan Stanley Children's Hospital

New York, New York, United States

Levine Children's Hospital - Hematology

Charlotte, North Carolina, United States

TriStar Medical Group Children's Specialists - Pediatric Oncology

Nashville, Tennessee, United States

University Hospital Dusseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology

Düsseldorf, Germany

IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica

Rome, Italy

King Faisal Specialist Hospital & Research Centre - Riyadh - Hematology

Al Mathar Ash Shamali, Saudi Arabia

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NCT05477563


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