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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-003555-11 | EudraCT Number |
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| Name | Class |
|---|---|
| URC-CIC Paris Descartes Necker Cochin | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARTEGENE drug product | Experimental | Autologous purified CD34+ cells transduced with a self-inactivated lentiviral vector, expressing the DCLRE1C gene (alias Artemis) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ARTEGENE drug product | Genetic | Each patient will receive a single intravenous infusion of ARTEGENE drug product at D0. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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) | by qPCR | Up to 15 years post treatment |
| Transgene copy number on sorted cell populations | Determined on sorted cell populations CD15+,CD14+, CD19+, CD56+ and CD3+ T lymphocytes by qPCR | Up to 15 years post treatment |
| 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 | by RT-qPCR performed on the transduced CD34+ cells in the drug substance and on peripheral blood mononuclear cells (PBMC) | At Day 0, 12 months and 24 months post treatment |
| Adverse events | Frequency and severity of clinical AEs and changes in laboratory parameters | Up to 15 years post treatment |
| Transgene copy number in the transduced CD34+ cells in the drug substance |
| Measure | Description | Time Frame |
|---|---|---|
| End of ongoing infection before the transplantation | Up to 15 years post treatment | |
| Kinetics of immune reconstitution | Kinetics of immune reconstitution | Up to 15 years post treatment |
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Inclusion Criteria:
Exclusion Criteria
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marina CAVAZZANA, MD, PhD | Contact | +33 144495068 | m.cavazzana@aphp.fr | |
| Jinmi BAEK, Master | Contact | +33 1 42 19 28 49 | jinmi.baek@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Alessandra MAGNANI, MD, PhD | Department of Biotherapy,LTCG, Necker-Enfants Malades Hospital | Study Director |
| Chantal Lagresle-Peyrou, MD | Imagine | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Pediatric Immunology, Hematology and Rheumatology UIHR, Necker-Enfants Malades Hospital | Recruiting | Paris | 75015 | France |
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by qPCR |
| At Day 0 |
| Change in total number of T cells | by flow cytometry | 6, 12, 24 months post treatment |
| Change in distribution of different subpopulations | 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 | 6, 12, 24 months post treatment |
| 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 | via high-throughput sequencing of the TCR | 12, 24 months post treatment |
| Evaluation of the B lymphocyte compartment | 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) | 6 months post treatment |
| Evaluation of the B lymphocyte compartment | 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) | At 12 months post treatment |
| Evaluation of the B lymphocyte compartment | 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) | At 24 months post treatment |
| Adverse event | Adverse event will be measured using CTCAE | Up to 15 years post treatment |
| ID | Term |
|---|---|
| C537589 | Severe combined immunodeficiency with sensitivity to ionizing radiation |
| C562592 | Xeroderma Pigmentosum, Complementation Group F |
| D016511 | Severe Combined Immunodeficiency |
| ID | Term |
|---|---|
| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| D049914 | DNA Repair-Deficiency Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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