Sickle Cell Disease MedDRA version: 21.0 Level: PT Classification code 10040644 Term: Sickle cell disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
bluebird bio, Inc.
Eligibility
Sex/Gender
All
Inclusion 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 (=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Applicable to subjects 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 9. Unable to receive red blood cell (RBC) transfusion. 10. Prior receipt of an allogeneic HSC transplant. 11. Prior receipt of gene therapy. 12. Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin. 13. Immediate family member with a known or suspected Familial Cancer Syndrome. 14. Pregnancy, or breastfeeding in a postpartum female, or absence of adequate contraception for fertile subjects. 15. Any other condition that would render the subject ineligible for HSCT. 16. Participation in another clinical study with an investigational drug within 30 days of screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of treatment with LentiGlobin BB305 Drug Product in subjects with sickle cell disease (SCD).;Secondary Objective: To evaluate the safety of treatment with LentiGlobin BB305 Drug Product in subjects with SCD;Primary end point(s): Proportion of subjects meeting Globin Response criteria Subjects must meet the below criteria for a continuous period of at least 6 months after drug product infusion in order to be considered having achieved Globin response: a. Weighted average HbAT87Q percentage of total Hb* =30% AND b. Weighted average total Hb* increase of =3 g/dL compared to baseline total Hb* OR weighted average total Hb* =10 g/dL -total Hb is the non-transfused total Hb; it is HbS + HbF + HbA2 + HbAT87Q ;Timepoint(s) of evaluation of this end point: 1-24 months post-transplant | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Percent of subjects reaching a 75% reduction in annualized severe vaso-occlusive events (sVOE-75) in the 24 months after drug product administration compared to the 24 months prior to Informed Consent. •Weighted average non-transfused total Hb •Weighted average HbS percentage of non-transfused total Hb •Weighted average HbS percentage of non-transfused total Hb =70%, =60%, =50% •Weighted average HbAT87Q percentage of non-transfused total Hb •Weighted average non-HbS percentage of non-transfused total Hb •Average and median of non-transfused total Hb over time •Average and median of HbS percentage of non-transfused total Hb over time •Average and median of HbAT87Q percentage of non-transfused total Hb over time •Average and median of non-HbS percentage of non-transfused total Hb over time •Change from baseline in absolute reticulocyte count •Change from baseline in percent reticulocytes •Change from baseline in percent erythrocytes •Change from baseline in total bilirubin •Change from baseline in haptoglobin •Change from baseline in lactate dehydrogenase •Change from baseline in iron •Change from baseline in ferritin •Change from baseline in transferrin saturation •Change from baseline in liver iron content •Change from baseline in cardiac iron content (if assessed at baseline) •Change from baseline in erythropoietin •Change from baseline in serum transferrin receptor •Change in the annualized number of severe VOEs in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent. •Change in the annualized number of VOEs in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent •Proportion of subjects achieving severe VOE-complete resolution (sVOE-CR) Defined as complete resolution of severe VOEs between 6 months and 24 months after drug product administration •Proportion of subjects achieving reduction in the annualized number of severe VOEs of at | — |
Countries
France, Germany, Italy, Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
bluebird bio, Inc.
Outcome results
None listed