A Study to Assess the Safety, Tolerability, and Efficacy of BIVV003 for Autologous Hematopoietic Stem Cell Transplantation in Patients With Severe Sickle Cell Disease

NCT03653247 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 003SCD101
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Sickle Cell Disease

Keywords

Intervention: Genetic: BIVV003; Drug: Busulfan; Biological: Plerixafor; Phase: Phase 1/2

Outcome Measures

Primary Outcomes (6)

• 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.

  Up to Week 104

Secondary Outcomes (22)

• 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

• 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

Study Arms (1)

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.

Biological: Plerixafor; Drug: Busulfan; Genetic: BIVV003

Interventions

Plerixafor BIOLOGICAL

Plerixafor subcutaneous injection will be administered prior to apheresis.

BIVV003

Busulfan DRUG

Busulfan IV infusion will be administered as myeloablative conditioning therapy.

BIVV003

BIVV003 GENETIC

BIVV003 will be administered as an IV infusion following myeloablative conditioning with busulfan.

Also known as: Autologous CD34 + hematopoietic stem cells

BIVV003

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Sangamo Therapeutics: lead

Study Sites (5)

UCSF Benioff Children's Hospital

Oakland, California, 94609, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Investigational Site Number 101

Bethesda, Maryland, 20892, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Related Publications (1)

• 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.

  PMID: 34175041 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

plerixafor; Busulfan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Medical Monitor

  Sangamo Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: August 31, 2018
• Study Start: March 6, 2019
• Primary Completion: July 17, 2025
• Study Completion: July 17, 2025
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)