Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат CTX001
  Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan

Первичные конечные точки

• Fetal Hemoglobin (HbF) Concentration Over Time [Срок оценки: Up to 12 Months After CTX001 Infusion]
• Total Hemoglobin (Hb) Concentration Over Time [Срок оценки: Up to 12 Months After CTX001 Infusion]

Вторичные конечные точки (12)

• TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: From Signing of Informed Consent up to 12 Months After CTX001 Infusion]
• TDT and SCD: Proportion of Participants With Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count (ANC) >=500 per Microliter [mcgL] on 3 Different Days) [Срок оценки: Within 42 Days After CTX001 Infusion]
• TDT and SCD: Time to Engraftment [Срок оценки: Up to 12 Months After CTX001 Infusion]
• TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion [Срок оценки: Within 100 Days After CTX001 Infusion]
• TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion [Срок оценки: Within 12 Months After CTX001 Infusion]
• TDT and SCD: Incidence of All-cause Mortality [Срок оценки: From Signing of Informed Consent up to 12 Months After CTX001 Infusion]
• TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions [Срок оценки: From Day 60 up to 12 Months After CTX001 Infusion]
• TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time [Срок оценки: Up to 12 Months After CTX001 Infusion]
• TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time [Срок оценки: Up to 12 Months After CTX001 Infusion]
• TDT: Duration Transfusion Free in Participants [Срок оценки: Up to 12 Months After CTX001 Infusion]
• SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs) [Срок оценки: From Baseline up to 12 Months After CTX001 Infusion]
• SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs [Срок оценки: From Baseline up to 12 Months After CTX001 Infusion]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• New York Presbyterian Hospital - Morgan Stanley Children's Hospital — New York
• Levine Children's Hospital - Hematology — Charlotte
• TriStar Medical Group Children's Specialists - Pediatric Oncology — Nashville

Германия · 1 центр

• University Hospital Dusseldorf - Department of Pediatric Oncology, Hematology and Clinical — Düsseldorf

Италия · 1 центр

• IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellula — Rome

Саудовская Аравия · 1 центр

• King Faisal Specialist Hospital & Research Centre - Riyadh - Hematology — Al Mathar Ash Shamali

Идентификаторы

NCT: NCT05477563 · VX21-CTX001-161 · 2024-514641-12-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗