Safety and Efficacy Study of Transplantation of Autologous CD34+ Cells Transduced With the G2ARTE Lentiviral Vector Expressing the DCLRE1C cDNA in Artemis (DCLRE1C) Deficient Severe Combined Immunodeficiency Patients (ARTEGENE)

Condition(s) studied

Investigational drug(s) / intervention(s)

ARTEGENE drug product: Each patient will receive a single intravenous infusion of ARTEGENE drug product at D0.

Study summary

The purpose of this study is to evaluate the Safety and Efficacy of Gene Therapy of the severe combined immunodeficiency (SCID) caused by mutations in the human DCLRE1C gene (Artemis) by transplantation of a single dose of autologous CD34+ cells transduced ex vivo with the G2ARTE lentiviral vector expressing the DCLRE1C cDNA.

Eligibility

Primary outcome measure(s)

• Incidence of transplant related mortality — Up to 100 days post treatment
• Incidence of transplant related mortality — At 6 months post treatment
• Transgene copy number on peripheral blood mononuclear cells (PBMCs) — Up to 15 years post treatment
  by qPCR
• Transgene copy number on sorted cell populations — Up to 15 years post treatment
  Determined on sorted cell populations CD15+,CD14+, CD19+, CD56+ and CD3+ T lymphocytes by qPCR
• Detection of replication-competent lentivirus (RCL) — 3 months post treatment
• Absence of any severe adverse events due to insertional mutagenesis — Up to 15 years post treatment
• Change in Artemis mRNA levels — At Day 0, 12 months and 24 months post treatment
  by RT-qPCR performed on the transduced CD34+ cells in the drug substance and on peripheral blood mononuclear cells (PBMC)
• Adverse events — Up to 15 years post treatment
  Frequency and severity of clinical AEs and changes in laboratory parameters
• Transgene copy number in the transduced CD34+ cells in the drug substance — At Day 0
  by qPCR
• Change in total number of T cells — 6, 12, 24 months post treatment
  by flow cytometry
• Change in distribution of different subpopulations — 6, 12, 24 months post treatment
  by flow cytometry, according to the WBC count: Naïve and activated/memory CD4+ and CD8+ T cells will be evaluated using CCR7/CD45RA/CD45RO markers. Early thymic emigrants will be monitored by detecting CD31+CD45RA+CD4+ T lymphocytes; Stem cell-like memory CD8+ and CD4+ T cells will be quantified by counting CCR7+CD45RA+CD8+ T cells. Evaluation of the distribution of TCRαβ and TCRγδ T cells
• Change in T lymphocyte in vitro proliferation in the presence of mitogens and antigens — 6, 12, 24 months post treatment
• Change in repertoire of T lymphocytes — 12, 24 months post treatment
  via high-throughput sequencing of the TCR
• Evaluation of the B lymphocyte compartment — 6 months post treatment
  analysis of the circulating B cell subpopulations by flow cytometry: total CD19+ cells, naive (CD19+IgD+CD27-), switched memory (CD19+IgD-CD27+), marginal zone (CD19+IgD+CD27+), transitional (CD19+IgD+CD27-CD24highCD38+), 21low (CD19+CD38-CD21low). Immunoglobulin levels (IgG, A, M and E) and specific antibody production after immunization (if applicable)
• Evaluation of the B lymphocyte compartment — At 12 months post treatment
  analysis of the circulating B cell subpopulations by flow cytometry: total CD19+ cells, naive (CD19+IgD+CD27-), switched memory (CD19+IgD-CD27+), marginal zone (CD19+IgD+CD27+), transitional (CD19+IgD+CD27-CD24highCD38+), 21low (CD19+CD38-CD21low). Immunoglobulin levels (IgG, A, M and E) and specific antibody production after immunization (if applicable)
• Evaluation of the B lymphocyte compartment — At 24 months post treatment
  analysis of the circulating B cell subpopulations by flow cytometry: total CD19+ cells, naive (CD19+IgD+CD27-), switched memory (CD19+IgD-CD27+), marginal zone (CD19+IgD+CD27+), transitional (CD19+IgD+CD27-CD24highCD38+), 21low (CD19+CD38-CD21low). Immunoglobulin levels (IgG, A, M and E) and specific antibody production after immunization (if applicable)

Trial sites (1)

More Assistance Publique - Hôpitaux de Paris trials in France