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 ß Thalassemia

Vertex Pharmaceuticals Incorporated0 sites45 target enrollmentJanuary 9, 2018

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: Vertex Pharmaceuticals Incorporated
Enrollment: 45
Status: Active, not recruiting
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

January 9, 2018

End Date

TBD

Last Updated

5 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Vertex Pharmaceuticals Incorporated

Eligibility Criteria

Inclusion Criteria

•1\. Subjects 12 to 35 years of age, inclusive on the date of informed consent
•2\. Subject (or their legally authorized representative or guardian) will sign and date an informed consent form (ICF) and, where applicable, an assent form
•3\. Diagnosis of transfusion\-dependent ß\-thalassemia (TDT) as defined by:
•a. Documented homozygous ß\-thalassemia or compound heterozygous ß\-thalassemia including ß\-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. The ß^0 and non ß^0 genotypes are defined using the HbVar Database.
•b. A 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 repeat screening.
•4\. Karnofsky performance status of \=80% for subjects \=16 years of age. Lansky performance status of \=80% for subjects \<16 years of age.
•5\. Eligible for autologous stem cell transplant as per investigator’s judgment.
•6\. Access to detailed medical records on packed RBC transfusions, including volume or units of packed RBCs and associated pre\-transfusion Hb values, and in\-patient hospitalizations, for at least the 2 years prior to consent.
•7\. Female subjects of childbearing potential (postmenarcheal, has an intact uterus and at least 1 ovary, and is less than 1 year postmenopausal) must agree to use acceptable method(s) of contraception from consent through at least 6 months after CTX001 infusion.

Exclusion Criteria

•1\. An available 10/10 Human Leukocyte Antigen (HLA)\-matched related donor.
•2\. Prior allo\-hematopoietic stem cell transplant (HSCT).
•3\. Subjects with associated a\-thalassemia and \>1 alpha chain deletion. or alpha multiplications.
•4\. Subjects with sickle cell beta thalassemia variant.
•5\. Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
•6\. White blood cell (WBC) count \<3 × 10^9/L or platelet count \<50 × 10^9/L not related to hypersplenism per investigator judgement.
•7\. History of a significant bleeding disorder.
•8\. History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to: immediate family member with a known family cancer syndrome, history of relevant drug allergies; history of cardiovascular or central nervous system disease; history or presence of clinically significant pathology; history of uncontrolled seizure disorders, or history of psychiatric disorders.
•9\. Any prior or current malignancy or myeloproliferative disorder or a significant immunodeficiency disorder.
•10\. Advanced liver disease, defined as: