- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04293185
A Study Evaluating Gene Therapy With BB305 Lentiviral Vector in Sickle Cell Disease
A Phase 3 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With the BB305 Lentiviral Vector in Subjects With Sickle Cell Disease
Study Overview
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: bluebird bio
- Phone Number: +1-833-999-6378
- Email: clinicaltrials@bluebirdbio.com
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35233
- Recruiting
- University of Alabama
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District of Columbia
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Washington, District of Columbia, United States, 20010
- Recruiting
- Children's National Hospital
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Massachusetts
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Boston, Massachusetts, United States, 02111
- Active, not recruiting
- Tufts Medical Center
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- Recruiting
- University of Minnesota
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Recruiting
- Hackensack University Medical Center
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New York
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Bronx, New York, United States, 10467
- Recruiting
- Montefiore Medical Center
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North Carolina
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Durham, North Carolina, United States, 27705
- Recruiting
- Duke University
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Texas
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Houston, Texas, United States, 77030
- Recruiting
- Baylor College of Medicine/Texas Children's Hospital
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Virginia
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Richmond, Virginia, United States, 23219
- Recruiting
- Virginia Commonwealth University (VCU)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Have a diagnosis of SCD, with either βS/βS, βS/β0, or βS/β+ genotype.
- Be ≥2 and ≤50 years of age at time of consent.
- Weigh a minimum of 6 kg.
- Have a Karnofsky performance status of ≥60 (≥16 years of age) or a Lansky performance status of ≥60 (<16 years of age).
- 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.
- In the setting of appropriate supportive care measures (e.g., pain management plan), have experienced at least 4 protocol-defined VOEs in the 24 months prior to informed consent.
- 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).
- Female and male subjects of childbearing potential agree to use 1 method of highly effective contraception from Screening to at least 6 months after drug product infusion.
- Provision of written informed consent for this study by subject, or as applicable, subject's parent(s)/legal guardian(s).
Exclusion Criteria:
- Subjects for whom allogeneic hematopoietic stem cell transplantation (allo-HSCT) is medically appropriate per PI judgment and a willing, human leukocyte antigen (HLA)-matched related hematopoietic stem cell donor is available.
- Severe cerebral vasculopathy, defined by any history of overt ischemic or hemorrhagic stroke, a history of abnormal transcranial Doppler (TCD) or TCD imaging (TCDI) for subjects ≤ 16 years of age (e.g. TCD velocity >200 cm/sec) requiring ongoing chronic transfusions, a Screening TCD or TCDI velocity > 200 cm/sec (central read), a Screening MRA showing > 50% stenosis or occlusion in the circle of Willis (central read), or a Screening MRA showing the presence of Moyamoya (central read).
- Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), hepatitis B, hepatitis C, human T-lymphotropic virus-1 (HTLV-1), active syphilis.
- Clinically significant, active bacterial, viral, fungal, or parasitic infection
Advanced liver disease, such as
- clear evidence of liver cirrhosis, active hepatitis or significant fibrosis (based on MRI or liver biopsy)
- liver iron concentration ≥15 mg/g unless liver biopsy shows no evidence of cirrhosis, active hepatitis or significant fibrosis
- 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.
- 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.
- Patients needing therapeutic anticoagulation treatment during the period of conditioning through platelet engraftment
- Unable to receive pRBC transfusion.
- Prior receipt of an allogeneic transplant.
- Prior receipt of gene therapy.
- Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin.
- Immediate family member with a known or suspected Familial Cancer Syndrome.
- Female subject is breastfeeding, pregnant or will attempt to become pregnant from Screening to at least 6 months after drug product infusion.
- Any other condition that would render the subject ineligible for HSCT.
- Participation in another clinical study with an investigational drug within 30 days of screening.
- Presence of a chromosomal abnormality or genetic mutation that may put the subject at an increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) per Investigator's judgment.
- Presence of genetic mutations that result in the inactivation of 2 or more α-globin genes
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: bb1111
Subjects will receive treatment with a single dose of Drug Product manufactured with autologous CD34+ hematopoietic stem cells collected by plerixafor mobilization and apheresis, transduced with BB305 lentiviral vector (LVV) encoding the human beta-A-T87Q globin gene. Plerixafor mobilization and apheresis will also be used for collection of rescue cells. |
Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
VOE-CR
Time Frame: 6-18 months post-transplant
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Proportion of subjects achieving complete resolution of VOEs between 6 months and 18 months after drug product infusion
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6-18 months post-transplant
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
sVOE-CR
Time Frame: 6-18 months post-transplant
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Proportion of subjects achieving complete resolution of severe vaso-occlusive events, between 6 months and 18 months after drug product infusion
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6-18 months post-transplant
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Proportion of subjects achieving Globin Response
Time Frame: 6-24 months post-transplant
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Globin Response, defined as meeting the following criteria for a continuous period of at least 6 months after drug product infusion:
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6-24 months post-transplant
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Change in the annualized number of VOEs in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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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.
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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VOE-CR24
Time Frame: 6-24 months post-transplant
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Proportion of subjects achieving complete resolution of VOEs between 6 months and 24 months after drug product infusion
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6-24 months post-transplant
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sVOE-CR24
Time Frame: 6-24 months post-transplant
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Proportion of subjects achieving complete resolution of severe VOEs between 6 months and 24 months after drug product infusion
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6-24 months post-transplant
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sVOE-75
Time Frame: 1-24 months post-transplant
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Proportion of subjects achieving at least a 75% reduction in annualized severe VOEs in the 24 months after drug product administration compared to the 24 months prior to Informed Consent.
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1-24 months post-transplant
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Weighted average non-transfused total Hb
Time Frame: Month 6, 12, 18 and 24 post-transplant
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Month 6, 12, 18 and 24 post-transplant
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Weighted average HbS percentage of non-transfused total Hb
Time Frame: Month 6, 12, 18 and 24 post-transplant
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Month 6, 12, 18 and 24 post-transplant
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Weighted average HbS percentage of non-transfused total Hb ≤70%, ≤60%, ≤50%
Time Frame: Month 6, 12, 18 and 24 post-transplant
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Month 6, 12, 18 and 24 post-transplant
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Weighted average HbAT87Q percentage of non-transfused total Hb
Time Frame: Month 6, 12, 18 and 24 post-transplant
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Month 6, 12, 18 and 24 post-transplant
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Weighted average non-HbS percentage of non-transfused total Hb
Time Frame: Month 6, 12, 18 and 24 post-transplant
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Month 6, 12, 18 and 24 post-transplant
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Average and median of non-transfused total Hb
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Average and median of HbS percentage of non-transfused total Hb
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Average and median of HbAT87Q percentage of non-transfused total Hb
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Average and median of non-HbS percentage of non-transfused total Hb
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Change from baseline in absolute reticulocyte count
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Change from baseline in percent reticulocytes
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Change from baseline in percent erythrocytes
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Change from baseline in total bilirubin
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Change from baseline in haptoglobin
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Change from baseline in lactate dehydrogenase
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Change from baseline in ferritin
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Change from baseline in liver iron content
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Change from baseline in cardiac iron content (if assessed at baseline)
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Change from baseline in erythropoietin
Time Frame: 1-24 months post-transplant
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1-24 months post-transplant
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Change from baseline in serum transferrin receptor
Time Frame: 1 - 24 months post-transplant
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1 - 24 months post-transplant
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Change from baseline in annualized frequency of packed red blood cell (pRBC) transfusions
Time Frame: 6-24 months post-transplant
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6-24 months post-transplant
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Change from baseline in annualized volume of pRBC transfusions
Time Frame: 6-24 months post-transplant
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6-24 months post-transplant
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Change from baseline in TCD velocity at Month 12 and Month 24 (for subjects ≤ 16 years old at Informed Consent)
Time Frame: Month 12 and Month 24 post-transplant
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Month 12 and Month 24 post-transplant
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Change from baseline in meters walked during the 6-minute walk test
Time Frame: 1 - 24 months post-transplant
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1 - 24 months post-transplant
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Change from baseline in annualized number of SCD-related hospital admissions
Time Frame: 1 - 24 months post-transplant
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1 - 24 months post-transplant
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Change from baseline in annualized number of total days hospitalized
Time Frame: 1 - 24 months post-transplant
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1 - 24 months post-transplant
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Change from baseline in patient-reported quality of life, as measured by PROMIS-57 Version 2.1 for subjects ≥ 18 years of age and PROMIS Pediatric Profile/Parent Proxy Profile 49 Version 2.0 for subjects < 18 years of age
Time Frame: 1 - 24 months post-transplant
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1 - 24 months post-transplant
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Anjulika Chawla, MD, FAAP, bluebird bio, Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HGB-210
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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