Efficacy and Safety of Cryopreserved Autologous Mobilized Peripheral Blood CD34+ HSPCs Transduced Ex Vivo With the EFS-ADA Lentiviral Vector in Patients With Severe Combined Immune Deficiency Due To Adenosine Deaminase Deficiency
The aim of this study is to assess the safety and efficacy of autologous transplantation of hematopoietic stem cells (CD34+ cells) from mobilized peripheral blood (mPB) of ADA-deficient SCID infants and children following human ADA gene transfer by the EFS-ADA lentiviral vector. The level of gene transfer in blood cells and immune function will be measured as endpoints.
‣ All subjects must fulfill the following criteria to be included in the study:
• Provision of written informed consent prior to any study related procedures. In this study consent must be provided by the parents/legal guardians and, where applicable according to local laws, a signed assent from the child,
• Subjects ≥30 days of age,
• With a diagnosis of ADA-SCID based on:
• Evidence of ADA deficiency, defined as:
• i. Decreased ADA enzymatic activity in erythrocytes, leukocytes, skin fibroblasts, or in cultured fetal cells to levels consistent with ADA-SCID as determined by the reference laboratory, or ii. Identified mutations in ADA alleles consistent with a severe reduction in ADA activity,
• Evidence of ADA-SCID based on either:
• i. Family history of a first order relative with ADA deficiency and clinical and laboratory evidence of severe immunologic deficiency, or ii. Evidence of severe immunologic deficiency in subjects prior to the institution of immune restorative therapy, based on
⁃ Lymphopenia (absolute lymphocyte count (ALC) \<400 cells/mL) OR absence or low number of T cells (absolute CD3+ count \< 300 cells/mL), or
⁃ Severely decreased T lymphocyte blastogenic responses to phytohemagglutinin (either \<10% of lower limit of normal controls for the diagnostic laboratory, or \<10% of the response of the normal control of the day, or stimulation index \<10), or
⁃ Identification of SCID by neonatal screening revealing low T Cell Receptor Excision Circles (TREC) levels.
• Ineligible for matched family allogeneic bone marrow (BM) transplantation, defined as the absence of a medically eligible HLA-identical sibling or family donor, with normal immune function, who could serve as an allogeneic bone marrow donor.
• Females of child-bearing age will be required to provide a negative pregnancy test 30 days prior to Visit 2.
• Subjects and their parents/legal guardians must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period and willing to return to the clinic for the follow up evaluation as specified in the protocol.