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A Safety and Efficacy Study Evaluating CTX001 in Subjects With Transfusion-Dependent β-Thalassemia

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ClinicalTrials.gov Identifier: NCT03655678
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
Vertex Pharmaceuticals Incorporated
Information provided by (Responsible Party):
CRISPR Therapeutics

August 29, 2018
August 31, 2018
November 14, 2018
September 14, 2018
February 2021   (Final data collection date for primary outcome measure)
  • Proportion of subjects achieving transfusion reduction for at least 6 months (TR6) [ Time Frame: From 9 to 24 months post-CTX001 infusion ]
  • Proportion of subjects with engraftment (absolute neutrophil count [ANC] ≥500/µL for three consecutive days) [ Time Frame: From 15 to 24 months post-CTX001 infusion ]
  • Time to neutrophil and platelet engraftment [ Time Frame: Days post-infusion to engraftment ]
  • Frequency and severity of collected adverse events (AEs) [ Time Frame: Signing of informed consent through Month 24 visit ]
  • Incidence of transplant-related mortality (TRM) [ Time Frame: Baseline (pre-transfusion) to 100 days and 1 year post-CTX001 infusion ]
  • All-cause mortality [ Time Frame: Signing of informed consent through Month 24 visit ]
Proportion of subjects achieving transfusion reduction for at least 6 months (TR6) [ Time Frame: From 9 to 24 months post-CTX001 infusion ]
Complete list of historical versions of study NCT03655678 on ClinicalTrials.gov Archive Site
  • Proportion of subjects achieving transfusion independence for at least 6 months (TI6) [ Time Frame: From 9 to 24 months post-CTX001 infusion ]
  • Proportion of subjects achieving TR12 [ Time Frame: From 15 to 24 months post-CTX001 infusion ]
  • Proportion of subjects achieving TI12 [ Time Frame: From 15 to 24 months post-CTX001 infusion ]
  • Proportion of alleles with intended genetic modification in peripheral blood leukocytes over time [ Time Frame: Day 1 CTX001 infusion through Month 24 visit ]
  • Proportion of alleles with intended genetic modification in bone marrow cells over time [ Time Frame: Day 1 CTX001 infusion through Month 24 visit ]
  • Change in fetal hemoglobin concentration over time [ Time Frame: Baseline (pre-transfusion) through Month 24 visit ]
  • Change in health-related quality of life (HRQoL) from baseline over time using EuroQol Questionnaire (5 dimensions - 5 levels of severity - EQ-5D-5L) [ Time Frame: Screening visit through Month 24 visit ]
    The EQ-5D-5L Questionnaire consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The EQ-5D comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and 5 levels: no problems to extreme problems. The subject marks the most appropriate statement in each dimension, resulting in a 1-digit number for that dimension. The digits can be combined in a 5-digit number describing the subject's health state. The EQ VAS records the subject's self-rated health on a 100-point VAS, endpoints labelled "the best health you can imagine" and "the worst health you can imagine."
  • Change in health-related quality of life (HRQoL) from baseline over time using the Functional assessment of cancer therapy-bone marrow transplant questionnaire (FACT-BMT) [ Time Frame: Screening visit through Month 24 visit ]
    The FACT-BMT Questionnaire includes physical, social, family, emotional, and functional well-being, and treatment specific concerns of bone marrow transplantation. Each statement has a 5-point Likert-type response scale ranging from 0=not at all to 4=very much. The subject marks one number per line as it applies to the past 7 days. Questionnaires are scored; the higher the score, the better the QOL.
  • Changes in liver iron concentration (LIC) and cardiac iron content (CIC) parameters of iron overload [ Time Frame: Screening visit through Month 24 visit ]
  • Proportion of subjects receiving iron chelation therapy [ Time Frame: Baseline (pre-transfusion) through Month 24 visit ]
  • Proportion of subjects achieving transfusion independence for at least 6 months (TI6) [ Time Frame: From 9 to 24 months post-CTX001 infusion ]
  • Proportion of subjects with engraftment (absolute neutrophil count [ANC] ≥500/µL for three consecutive days) [ Time Frame: From 15 to 24 months post-CTX001 infusion ]
  • Proportion of subjects achieving TR12 [ Time Frame: From 15 to 24 months post-CTX001 infusion ]
  • Proportion of subjects achieving TI12 [ Time Frame: From 15 to 24 months post-CTX001 infusion ]
  • Time to neutrophil and platelet engraftment [ Time Frame: Days post-infusion to engraftment ]
  • Frequency and severity of collected adverse events (AEs) [ Time Frame: Signing of informed consent through Month 24 visit ]
  • Incidence of transplant-related mortality (TRM) [ Time Frame: Baseline (pre-transfusion) to 100 days and 1 year post-CTX001 infusion ]
  • All-cause mortality [ Time Frame: Signing of informed consent through Month 24 visit ]
  • Proportion of alleles with intended genetic modification in peripheral blood leukocytes over time [ Time Frame: Day 1 CTX001 infusion through Month 24 visit ]
  • Proportion of alleles with intended genetic modification in bone marrow cells over time [ Time Frame: Day 1 CTX001 infusion through Month 24 visit ]
  • Change in fetal hemoglobin concentration over time [ Time Frame: Baseline (pre-transfusion) through Month 24 visit ]
  • Change in health-related quality of life (HRQoL) from baseline over time using EuroQol Questionnaire (5 dimensions - 5 levels of severity - EQ-5D-5L) [ Time Frame: Screening visit through Month 24 visit ]
    The EQ-5D-5L Questionnaire consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The EQ-5D comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and 5 levels: no problems to extreme problems. The subject marks the most appropriate statement in each dimension, resulting in a 1-digit number for that dimension. The digits can be combined in a 5-digit number describing the subject's health state. The EQ VAS records the subject's self-rated health on a 100-point VAS, endpoints labelled "the best health you can imagine" and "the worst health you can imagine."
  • Change in health-related quality of life (HRQoL) from baseline over time using the Functional assessment of cancer therapy-bone marrow transplant questionnaire (FACT-BMT) [ Time Frame: Screening visit through Month 24 visit ]
    The FACT-BMT Questionnaire includes physical, social, family, emotional, and functional well-being, and treatment specific concerns of bone marrow transplantation. Each statement has a 5-point Likert-type response scale ranging from 0=not at all to 4=very much. The subject marks one number per line as it applies to the past 7 days. Questionnaires are scored; the higher the score, the better the QOL.
  • Changes in liver iron concentration (LIC) and cardiac iron content (CIC) parameters of iron overload [ Time Frame: Screening visit through Month 24 visit ]
  • Proportion of subjects receiving iron chelation therapy [ Time Frame: Baseline (pre-transfusion) through Month 24 visit ]
Not Provided
Not Provided
 
A Safety and Efficacy Study Evaluating CTX001 in Subjects With Transfusion-Dependent β-Thalassemia
A Phase 1/2 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
This is a single-arm, open-label, multi-site, single-dose Phase 1/2 study in up to 12 subjects 18 to 35 years of age with transfusion-dependent β-thalassemia (TDT), non-β0/β0. The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) using CTX001.
The study may be expanded to include up to 45 subjects.
Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Beta-Thalassemia
  • Thalassemia
  • Genetic Diseases, Inborn
  • Hematologic Diseases
  • Hemoglobinopathies
Biological: CTX001
Administered by IV infusion following myeloablative conditioning with busulfan
Experimental: CTX001
CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Subjects will receive a single infusion of CTX001 through a central venous catheter.
Intervention: Biological: CTX001
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
45
30
May 2022
February 2021   (Final data collection date for primary outcome measure)

Key Inclusion Criteria:

  • Subjects ≥18 and ≤35 years of age.
  • Diagnosis of transfusion-dependent β-thalassemia (TDT) as defined by:

    1. Documented homozygous β-thalassemia (with the exception of the β0/β0 genotype) or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Subjects 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.
  • Eligible for autologous stem cell transplant as per investigator's judgment.

Key Exclusion Criteria:

  • An available 10/10 Human Leukocyte Antigen (HLA)-matched related donor.
  • Prior allo-HSCT.
  • Subjects with associated α-thalassemia and >1 alpha chain deletion.
  • β0/β0 thalassemia genotype or 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.

Sexes Eligible for Study: All
18 Years to 35 Years   (Adult)
No
Contact: CRISPR Therapeutics Clinical Operations 617-315-4600 CTX001-111@crisprtx.com
Germany,   United Kingdom
 
 
NCT03655678
CTX001-111
Yes
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Plan to Share IPD: No
CRISPR Therapeutics
CRISPR Therapeutics
Vertex Pharmaceuticals Incorporated
Study Director: John Chapin, MD CRISPR Therapeutics
CRISPR Therapeutics
November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP