A Phase 3 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo with the LentiGlobin BB305 Lentiviral Vector in Subjects with Sickle Cell Disease.

bluebird bio, Inc.0 sites35 target enrollmentNovember 13, 2020

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: bluebird bio, Inc.
Enrollment: 35
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

November 13, 2020

End Date

TBD

Last Updated

5 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

bluebird bio, Inc.

Eligibility Criteria

Inclusion Criteria

•1\. Have a diagnosis of SCD, with either ßS/ßS, ßS/ß0 or ßS/ß\+ genotype.
•2\. Be \=2 and \=50 years of age at time of consent.
•3\. Weigh a minimum of 6 kg.
•4\. Have a Karnofsky performance status of \=60 (\=16 years of age) or a Lansky performance status of \=60 (\<16 years of age).
•5\. Be treated and followed for at least the past 24 months prior to Informed Consent in medical center(s) that maintained detailed records on sickle cell disease history.
•6\. Have severe manifestations of SCD. i.e. in the setting of appropriate supportive care measures (e.g., pain management plan), have experienced at least 4 severe VOEs in the 24 months prior to informed consent as defined below. For the purposes of this study, a severe VOE is defined as an event with no medically determined cause other than a vaso\-occlusion, requiring a \=24 \-hour hospital or emergency room (ER) observation unit visit or at least 2 visits to a day unit or ER over 72 hours with both visits requiring intravenous treatment. Exception: priapism does not require hospital admission but does require a medical facility visit; 4 priapism episodes that require a visit to a medical facility (without inpatient admission) are sufficient to meet criterion.
•7\. Have either experienced HU failure at any point in the past or must have intolerance to HU (intolerance is defined as the patient being unable to continue to take HU per PI judgment).
•Are the trial subjects under 18? yes
•Number of subjects for this age range: 20
•F.1\.2 Adults (18\-64 years) yes

Exclusion Criteria

•1\. Applicable to subjects \<18 years of age only: Availability of a willing, matched human leukocyte antigen (HLA)\-identical sibling HSC donor.
•2\. Severe cerebral vasculopathy, defined by any history of: overt ischemic or hemorrhagic stroke, abnormal transcranial Doppler (\>200 cm/sec based on central read) requiring chronic transfusion, occlusion or stenosis in the circle of Willis, or presence of Moyamoya disease.
•3\. Positive for presence of human immunodeficiency virus type 1 or 2 (HIV\-1 or HIV\-2\), hepatitis B, hepatitis C, human T\-lymphotrophic virus\-1 (HTLV\-1\) or \-2 (HTLV\-2\), active syphilis.
•4\. Clinically significant, active bacterial, viral, fungal, or parasitic infection
•5\. Advanced liver disease, such as
•a. clear evidence of liver cirrhosis, active hepatitis or significant fibrosis (based on MRI or liver biopsy)
•b. liver iron concentration \=15 mg/g unless liver biopsy shows no evidence of cirrhosis, active hepatitis or significant fibrosis
•6\. Inadequate bone marrow function, as defined by an absolute neutrophil count of \<1×10^9/L (\<0\.5×10^9/L for subjects on hydroxyurea treatment) or a platelet count \<100×10^9/L.
•7\. Any contraindications to the use of plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.
•8\. Patients needing therapeutic anticoagulation treatment during the period of conditioning through platelet engraftment