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This is an open label, multicenter, Phase 1/2 study in approximately eight adults with severe Sickle Cell Disease (SCD). The study will evaluate the safety, tolerability, and efficacy of autologous hematopoietic stem cell transplantation using BIVV003.
Subject participation in this study will be approximately 136 weeks. Enrolled subjects will be asked to participate in a separate long-term follow-up study to monitor the safety and efficacy of BIVV003 treatment for a total of 15 years post-transplant.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BIVV003 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Plerixafor | Biological | Plerixafor subcutaneous injection will be administered prior to apheresis. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants who are Alive at Post-transplantation Day 100 | The percentage of participants who are alive at post-transplantation Day 100 will be calculated using the Kaplan-Meier estimate. | Day 100 |
| Percentage of Participants who are Alive at Post-transplantation Week 52 | The percentage of participants who are alive at post-transplantation Week 52 will be calculated using the Kaplan-Meier estimate. | Week 52 |
| Percentage of Participants who are Alive at Post-transplantation Week 104 | The percentage of participants who are alive at post-transplantation Week 104 will be calculated using the Kaplan-Meier estimate. | Week 104 |
| Percentage of Participants With Successful Engraftment | Successful engraftment is defined by absolute neutrophil count (ANC) greater than or equal to >=500 cells/microliter (mL) for 3 consecutive days. | Up to Day 42 |
| Number of Participants With Adverse Events (AEs) | 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. | Up to Week 104 |
| Number of Participants With Serious Adverse Events (SAEs) | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| CD34 + HSPC Yield from Plerixafor Stem Cell Mobilization | Approximately 12 weeks | |
| Proportion of Participants with Sufficient Stem Cell Mobilization for Rescue Aliquot and BIVV003 Production | Approximately 12 weeks |
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Inclusion Criteria
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Sangamo Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Benioff Children's Hospital | Oakland | California | 94609 | United States | ||
| University of California Davis Comprehensive Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34175041 | Derived | Brusson M, Miccio A. Genome editing approaches to beta-hemoglobinopathies. Prog Mol Biol Transl Sci. 2021;182:153-183. doi: 10.1016/bs.pmbts.2021.01.025. Epub 2021 Mar 1. |
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| Busulfan | Drug | Busulfan IV infusion will be administered as myeloablative conditioning therapy. |
|
| BIVV003 | Genetic | BIVV003 will be administered as an IV infusion following myeloablative conditioning with busulfan. |
|
|
| Up to Week 104 |
| Yield of Zinc Finger Nuclease (ZFN)-edited Investigational Product | Approximately 12 weeks |
| Time to Initial Neutrophil Recovery Following BIVV003 Infusion | Up to Week 104 |
| Time to Platelet Recovery Following BIVV003 Infusion | Up to Week 104 |
| Percentage of Participants With Maintenance of Absolute Neutrophil Count (ANC) of >=500/mcL to last Participant Visit | Percentage of participants maintaining ANC of >=500/mcL to last Participant Visit (Week 104) will be calculated. | Up to Week 104 |
| Percentage of Participants With Maintenance of Platelet count of >=50,000/mcL to last Participant Visit | 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. | Up to Week 104 |
| Change From Baseline in Peripheral Blood Fetal Hemoglobin (HbF) Levels | Change from baseline in HbF up to Week 104 will be assessed. | Baseline up to Week 104 |
| Change From Baseline in Peripheral Blood Percent (%)F cells | Change from baseline in %F cells up to Week 104 will be assessed. | Baseline up to Week 104 |
| Change From Baseline in Peripheral Blood Sickle Hemoglobin (HbS) Levels | Change from baseline in peripheral blood HbS levels up to Week 104 will be assessed. | Baseline up to Week 104 |
| Change From Baseline in Peripheral blood total hemoglobin (Hb) concentration | Change From baseline in peripheral blood total hemoglobin (Hb) concentration up to week 104 will be assessed. | Baseline up to Week 104 |
| Change From Baseline in Reticulocyte Count | Change from baseline in reticulocyte count up to Week 104 will be assessed. | Baseline up to Week 104 |
| Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change from baseline in LDH levels up to Week 104 will be assessed. | Baseline up to Week 104 |
| Change From Baseline in Haptoglobin Levels | Change from baseline in haptoglobin levels up to Week 104 will be assessed. | Baseline up to Week 104 |
| Change From Baseline in Serum Bilirubin Levels | Change from baseline in serum bilirubin levels up to Week 104 will be assessed. | Baseline up to Week 104 |
| Change From Baseline in Patient-Reported Outcomes Measurement Information System 57 (PROMIS-57) Scale Score | 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. | Baseline up to Week 104 |
| Number of Participants With Sickle Cell Disease (SCD)-related Clinical Events | Number of participants with SCD-related clinical events (including vaso-occlusive crisis [VOC], pain episodes etc.) will be reported. | Baseline up to Week 104 |
| Number of SCD Related Clinical Events by Severity | 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. | Baseline up to Week 104 |
| Participants lymphocyte Counts | Lymphocyte counts will be measured to assess reconstitution of immune function post-BIVV003 transplantation. | At Weeks 13 and 52 |
| Participants Immunoglobulin levels | Immunoglobulin levels will be measured to assess reconstitution of immune function post-BIVV003 transplantation. | At Weeks 13 and 52 |
| Number of Red Blood Cell (RBC) Transfusions Received During the Post-transplantation Study Period | The number of RBC transfusions received during the Post-Transplantation study period will be reported. | Up to Week 104 |
| Total Volume of RBC Transfused | Total volume of RBC transfused during the Post-Transplantation study period will be reported. | Up to Week 104 |
| Sacramento |
| California |
| 95817 |
| United States |
| Children's Healthcare of Atlanta | Atlanta | Georgia | 30322 | United States |
| Investigational Site Number 101 | Bethesda | Maryland | 20892 | United States |
| Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C088327 | plerixafor |
| D002066 | Busulfan |
| ID | Term |
|---|---|
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D008698 | Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
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