A Phase 1/2 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Severe Sickle Cell Disease

Vertex Pharmaceuticals Incorporated0 sites45 target enrollmentMay 31, 2018

Overview

No summary available.

Registry

who.int

Start Date

May 31, 2018

End Date

TBD

Last Updated

5 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Sponsor

•1\. Subject (or their legally authorized representative or guardian) will sign and date an informed consent form (ICF) and, where applicable, an assent form.
•2\. Subjects 12 to 35 years of age, inclusive on the date of informed consent.
•3\. Documented ßS/ßS or ßS/ß0 genotype. Subjects can be enrolled based on historical genotype results, but confirmation of genotype is required before busulfan conditioning. The ß0 genotypes are defined using the HbVar Database.
•4\. Subjects with severe SCD. Severe SCD is defined by the occurrence of at least 2 of the following events per year during the 2\-year period before screening, while receiving appropriate supportive care (e.g., pain management plan, HU):
•Acute pain events that requires a visit to a medical facility and
•administration of pain medications (opioids or intravenous \[IV] nonsteroidal
•anti\-inflammatory drugs \[NSAIDs]) or RBC transfusions
•Acute chest syndrome, as indicated by the presence of a new
•pulmonary infiltrate associated with pneumonia\-like symptoms, pain, or fever
•Priapism lasting \>2 hours and requiring a visit to a medical facility

•1\. An available 10/10 human leukocyte antigen (HLA)\-matched related donor.
•2\. Prior Hematopoietic Stem Cell Transplant (HSCT).
•3\. Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
•4\. White blood cell (WBC) count \<3 × 109/L or platelet count \<50 × 109/L, not related to hypersplenism per investigator judgment.
•5\. Treatment with regular RBC transfusions that, in the opinion of the investigator, cannot be interrupted after engraftment.
•6\. Subjects with history of alloimmunization to RBC antigens and for whom the investigator anticipates that there will be insufficient RBC units available for the duration of the study.
•7\. More than 10 unplanned hospitalizations or emergency department visits related to SCD in the 1 year before screening that, in the opinion of the investigator, are consistent with significant chronic pain rather than acute pain crises.
•8\. HbF level \>15\.0%, irrespective of concomitant treatment with HbF\-inducing treatments such as HU.
•9\. History of abnormal TCD (TAMMV \=200 cm/sec) for subjects 12 to 18 years of age.
•10\. History of untreated Moyamoya disease or presence of Moyamoya disease at Screening that in the opinion of the investigator puts the subjects at the risk of bleeding.