A Study to Assess the Safety, Tolerability, and Efficacy of BIVV003 for Autologous Hematopoietic Stem Cell Transplantation in Patients With Severe Sickle Cell Disease
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ClinicalTrials.gov Identifier: NCT03653247 |
Recruitment Status :
Recruiting
First Posted : August 31, 2018
Last Update Posted : September 15, 2022
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Condition or disease | Intervention/treatment | Phase |
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Sickle Cell Disease | Biological: Plerixafor Drug: Busulfan Genetic: BIVV003 | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 8 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1/2, Open-Label, Multicenter, Single-Arm Study to Assess the Safety, Tolerability, and Efficacy of BIVV003 for Autologous Hematopoietic Stem Cell Transplantation in Patients With Severe Sickle Cell Disease |
Actual Study Start Date : | March 6, 2019 |
Estimated Primary Completion Date : | August 9, 2024 |
Estimated Study Completion Date : | August 9, 2024 |

Arm | Intervention/treatment |
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Experimental: BIVV003
Participants will receive plerixafor as subcutaneous (SQ) administration followed by myeloablative conditioning therapy with intravenous (IV) busulfan. BIVV003 will then be administered as a 1-time IV infusion of autologous Cluster of Differentiation 34 + Hematopoietic Stem/Progenitor Cell (CD34+HSPC) transfected ex vivo with zinc finger nuclease (ZFN) messenger ribonucleic acid (mRNAs) targeting the B-cell lymphoma/leukemia 11A (BCL11A) locus.
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Biological: Plerixafor
Plerixafor subcutaneous injection will be administered prior to apheresis. Drug: Busulfan Busulfan IV infusion will be administered as myeloablative conditioning therapy. Genetic: BIVV003 BIVV003 will be administered as an IV infusion following myeloablative conditioning with busulfan.
Other Name: Autologous CD34 + hematopoietic stem cells |
- Percentage of Participants who are Alive at Post-transplantation Day 100 [ Time Frame: Day 100 ]The percentage of participants who are alive at post-transplantation Day 100 will be calculated using the Kaplan-Meier estimate.
- Percentage of Participants who are Alive at Post-transplantation Week 52 [ Time Frame: Week 52 ]The percentage of participants who are alive at post-transplantation Week 52 will be calculated using the Kaplan-Meier estimate.
- Percentage of Participants who are Alive at Post-transplantation Week 104 [ Time Frame: Week 104 ]The percentage of participants who are alive at post-transplantation Week 104 will be calculated using the Kaplan-Meier estimate.
- Percentage of Participants With Successful Engraftment [ Time Frame: Up to Day 42 ]Successful engraftment is defined by absolute neutrophil count (ANC) greater than or equal to >=500 cells/microliter (mL) for 3 consecutive days.
- Number of Participants With Adverse Events (AEs) [ Time Frame: Up to Week 104 ]An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
- Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to Week 104 ]An SAE is any untoward medical occurrence that at any dose: Results in death, in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); however, this does not include an event that, had it occurred in a more severe form, might have caused death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.
- CD34 + HSPC Yield from Plerixafor Stem Cell Mobilization [ Time Frame: Approximately 12 weeks ]
- Proportion of Participants with Sufficient Stem Cell Mobilization for Rescue Aliquot and BIVV003 Production [ Time Frame: Approximately 12 weeks ]
- Yield of Zinc Finger Nuclease (ZFN)-edited Investigational Product [ Time Frame: Approximately 12 weeks ]
- Time to Initial Neutrophil Recovery Following BIVV003 Infusion [ Time Frame: Up to Week 104 ]
- Time to Platelet Recovery Following BIVV003 Infusion [ Time Frame: Up to Week 104 ]
- Percentage of Participants With Maintenance of Absolute Neutrophil Count (ANC) of >=500/mcL to last Participant Visit [ Time Frame: Up to Week 104 ]Percentage of participants maintaining ANC of >=500/mcL to last Participant Visit (Week 104) will be calculated.
- Percentage of Participants With Maintenance of Platelet count of >=50,000/mcL to last Participant Visit [ Time Frame: Up to Week 104 ]The percentage of participants attaining a post-transplant platelet count of >=50,000/mcL and maintaining this level through last Participant Visit (Week 104) will be calculated.
- Change From Baseline in Peripheral Blood Fetal Hemoglobin (HbF) Levels [ Time Frame: Baseline up to Week 104 ]Change from baseline in HbF up to Week 104 will be assessed.
- Change From Baseline in Peripheral Blood Percent (%)F cells [ Time Frame: Baseline up to Week 104 ]Change from baseline in %F cells up to Week 104 will be assessed.
- Change From Baseline in Peripheral Blood Sickle Hemoglobin (HbS) Levels [ Time Frame: Baseline up to Week 104 ]Change from baseline in peripheral blood HbS levels up to Week 104 will be assessed.
- Change From Baseline in Peripheral blood total hemoglobin (Hb) concentration [ Time Frame: Baseline up to Week 104 ]Change From baseline in peripheral blood total hemoglobin (Hb) concentration up to week 104 will be assessed.
- Change From Baseline in Reticulocyte Count [ Time Frame: Baseline up to Week 104 ]Change from baseline in reticulocyte count up to Week 104 will be assessed.
- Change From Baseline in Lactate Dehydrogenase (LDH) Levels [ Time Frame: Baseline up to Week 104 ]Change from baseline in LDH levels up to Week 104 will be assessed.
- Change From Baseline in Haptoglobin Levels [ Time Frame: Baseline up to Week 104 ]Change from baseline in haptoglobin levels up to Week 104 will be assessed.
- Change From Baseline in Serum Bilirubin Levels [ Time Frame: Baseline up to Week 104 ]Change from baseline in serum bilirubin levels up to Week 104 will be assessed.
- Change From Baseline in Patient-Reported Outcomes Measurement Information System 57 (PROMIS-57) Scale Score [ Time Frame: Baseline up to Week 104 ]Quality of life (QoL) measures including fatigue will be assessed using PROMIS-57 scale. This is a 57-item questionnaire with 8 questions per domain for assessing physical and mental well-being in participants with SCD. 57 questions are summed into a total score, which is transformed into an age specific normalized t-score with 50 representing normal, and lower scores representing increasing disability.
- Number of Participants With Sickle Cell Disease (SCD)-related Clinical Events [ Time Frame: Baseline up to Week 104 ]Number of participants with SCD-related clinical events (including vaso-occlusive crisis [VOC], pain episodes etc.) will be reported.
- Number of SCD Related Clinical Events by Severity [ Time Frame: Baseline up to Week 104 ]Severity will be categorized by toxicity grade according to CTCAE Version 5.0. AEs not listed in the CTCAE Version 5.0 will be evaluated by: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe or medically significant but not immediately life threatening, Grade 4=Life-threatening consequences; Grade 5=Death.
- Participants lymphocyte Counts [ Time Frame: At Weeks 13 and 52 ]Lymphocyte counts will be measured to assess reconstitution of immune function post-BIVV003 transplantation.
- Participants Immunoglobulin levels [ Time Frame: At Weeks 13 and 52 ]Immunoglobulin levels will be measured to assess reconstitution of immune function post-BIVV003 transplantation.
- Number of Red Blood Cell (RBC) Transfusions Received During the Post-transplantation Study Period [ Time Frame: Up to Week 104 ]The number of RBC transfusions received during the Post-Transplantation study period will be reported.
- Total Volume of RBC Transfused [ Time Frame: Up to Week 104 ]Total volume of RBC transfused during the Post-Transplantation study period will be reported.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 40 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
- Ages 18 to 40
- Confirmation of sickle cell disease (SCD) diagnosis (HbSS or HbS[beta]0 genotype)
- Severe SCD, defined as having 1 or more of the following manifestations: Clinically significant neurologic event (example [e.g.], stroke) or any neurological deficit lasting more than 24 hours; History of 2 or more episodes or Acute Chest Syndrome (ACS) in 2 years prior to informed consent (despite adequate supportive therapies such as asthma therapy); Six or more pain crises per year in 2 years prior to informed consent (requiring intravenous [IV] pain management in the outpatient or inpatient hospital setting); History of 2 or more cases or priapism with participant seeking medical care in the 2-years prior to informed consent; Regular RBC transfusion therapy in the year prior to informed consent (having received 8 or more transfusions to prevent vaso-occlusive clinical complications); and Echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity of greater than or equal to 2.5 meter per second (m/s)
- Clinically stable to undergo stem cell mobilization and myeloablative hematopoietic stem cell transplantation (HSCT)
- Adequate physiological function, defined as the following: Karnofsky/Lansky Performance of greater than or equal to 60; Acceptable cardiac function as defined in protocol; Acceptable pulmonary function as defined in protocol; Acceptable renal function as defined in protocol; and Acceptable hepatic function as defined in protocol
- Ability to understand purpose and risks of study, provide Informed Consent Form (ICF) and authorization to use protected health information
- Completion of age-appropriate cancer screening
- Willingness to use double-barrier method of contraception through entire study period (for participants of childbearing potential)
- Willingness to receive blood transfusions
- Willingness to discontinue hydroxyurea (HU) at least 30 days prior to stem cell mobilization through Day 100 post-transplantation
Exclusion Criteria:
- Previous receipt of an autologous or allogeneic HSCT or solid organ transplantation
- Previous treatment with gene therapy
- Current enrollment in an interventional study or having received an investigational drug within 30 days of study enrollment
- Pregnant or breastfeeding female
- Female or male who plans to become pregnant or impregnate a partner, respectively, during the anticipated study period
- Contraindication to plerixafor, apheresis, or busulfan
- Treatment with prohibited medication in previous 30 days
- Known allergy or hypersensitivity to plerixafor, busulfan, or investigational product excipients
- History of active malignancy within past 5 years, any history of hematologic malignancy, or a family history of a cancer predisposition syndrome (without negative result of candidate)
- Current diagnosis of uncontrolled seizures
- History of significant bleeding disorder
- Clinically significant infection
- Any major organ dysfunction involving brain, kidney, liver, lung, or heart (e.g., congestive heart failure, pulmonary hypertension)
- Corrected QT interval of more than 500 millisecond (ms) based on screening electrocardiogram (ECG)
- Positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
- Known to have a gamma-globin variant associated with altered oxygen affinity
- Hereditary persistence of fetal hemoglobin (HPFH) or HbF concentration of more than or equal to 20 percent (%) at screening
- Absolute Neutrophil Count (ANC) of less than or equal to 1,000 per microliter
- Platelet count of less than 100,000 per microliter
- History of platelet alloimmunization (precluding ability to provide transfusion support)
- Extensive Red Blood Cell (RBC) alloimmunization (precluding ability to provide transfusion support)
- Judged unsuitable for participation by investigator and/or sponsor

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03653247
Contact: Medical Monitor | 510-307-7266 | clinicaltrials@sangamo.com |
United States, California | |
UCSF Benioff Children's Hospital | Recruiting |
Oakland, California, United States, 94609 | |
Contact: Marci Moriarty, R.N. marci.moriarty@ucsf.edu | |
University of California Davis Comprehensive Cancer Center | Recruiting |
Sacramento, California, United States, 95817 | |
Contact: Leslie Mellor 916-417-2207 ljmellor@ucdavis.edu | |
United States, Georgia | |
Children's Healthcare of Atlanta | Recruiting |
Atlanta, Georgia, United States, 30322 | |
Contact: Judson Russell bmt@choa.org | |
United States, Maryland | |
Investigational Site Number 101 | Recruiting |
Bethesda, Maryland, United States, 20892 | |
Contact: Rick Gustafson Richard.gustafson@nih.gov | |
United States, Michigan | |
Karmanos Cancer Institute | Recruiting |
Detroit, Michigan, United States, 48201 | |
Contact: Marie Ventimiglia ventimim@karmanos.org | |
United States, Pennsylvania | |
Children's Hospital of Philadelphia_Investigational site number 108 | Recruiting |
Philadelphia, Pennsylvania, United States, 19104 | |
Contact: Janet Kwiatkowski, M.D. kwiatkowski@chop.edu |
Study Director: | Medical Monitor | Sangamo Therapeutics |
Responsible Party: | Sangamo Therapeutics |
ClinicalTrials.gov Identifier: | NCT03653247 |
Other Study ID Numbers: |
003SCD101 |
First Posted: | August 31, 2018 Key Record Dates |
Last Update Posted: | September 15, 2022 |
Last Verified: | March 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Intervention: Genetic: BIVV003 Drug: Busulfan Biological: Plerixafor Phase: Phase 1/2 |
Anemia, Sickle Cell Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn Plerixafor Busulfan Alkylating Agents Molecular Mechanisms of Pharmacological Action |
Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Alkylating Antineoplastic Agents Myeloablative Agonists Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents |