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)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: ARTEGENE drug product.
- Who it may be relevant to
- Registry conditions: Artemis (DCLRE1C ) Deficient Severe Combined Immunodeficiency. Basic parameters: up to 47 months · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Phase 1/2 Open Label Non Randomized Study, Multicentric, Single Arm Evaluating 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
Overview
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.
Interventions
- Genetic ARTEGENE drug product
Each patient will receive a single intravenous infusion of ARTEGENE drug product at D0.
Primary outcome measures
- Incidence of transplant related mortality [Time frame: Up to 100 days post treatment]
- Incidence of transplant related mortality [Time frame: At 6 months post treatment]
- Transgene copy number on peripheral blood mononuclear cells (PBMCs) [Time frame: Up to 15 years post treatment]
- Transgene copy number on sorted cell populations [Time frame: Up to 15 years post treatment]
- Detection of replication-competent lentivirus (RCL) [Time frame: 3 months post treatment]
- Absence of any severe adverse events due to insertional mutagenesis [Time frame: Up to 15 years post treatment]
- Change in Artemis mRNA levels [Time frame: At Day 0, 12 months and 24 months post treatment]
- Adverse events [Time frame: Up to 15 years post treatment]
- Transgene copy number in the transduced CD34+ cells in the drug substance [Time frame: At Day 0]
- Change in total number of T cells [Time frame: 6, 12, 24 months post treatment]
Secondary outcome measures (3)
- End of ongoing infection before the transplantation [Time frame: Up to 15 years post treatment]
- Kinetics of immune reconstitution [Time frame: Up to 15 years post treatment]
- Adverse event [Time frame: Up to 15 years post treatment]
Eligibility criteria
Inclusion criteria
- Patient to 47 months
- SCID patients with confirmed biallelic mutations in the Artemis (DCLRE1C) gene even in the case of leaky forms characterised by a residual activity
- Absence of an HLA genoidentical donor or without rapidly available HLA-compatible unrelated donor (within six weeks of diagnosis)
- The patient can be treated by gene therapy without delay in case of active life threatening infections compromising the short-term prognosis and for which the delay in finding a phenoidentical donor is incompatible with the patient's condition of health. Active life threatening infections are defined as: viral respiratory infection, CMV infection, adenovirus infection, disseminated BCGitis or other infections grade ≥ 4 according to CTCAE scale
- Beneficiary of a social security scheme
- Parental, guardian's patient signed informed consent.
Exclusion criteria
- Unwillingness to return for follow-up during the first 2 years study and the long term follow-up
- HIV-1 or 2 or HTLV1 infections
- Hypersensitivity to G-CSF, busulfan or Fludarabine
- Unable to tolerate general anesthesia and/or marrow harvest or peripheral blood stem cell collection (apheresis) or insertion of central venous catheter.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
France · 1 center
- Department of Pediatric Immunology, Hematology and Rheumatology UIHR, Necker-Enfants Malad — Paris
Identifiers
NCT: NCT05071222 · D20180302 · 2019-003555-11