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

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

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.

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