Clinical trial NCT05071222: 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)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Artemis (DCLRE1C ) Deficient Severe Combined Immunodeficiency
Keywords: Artemis deficient Severe Combined Immunodeficiency
Severe Combined Immunodeficiency
Gene therapy
Allogeneic hematopoietic stem cells transplantation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-10-08
Enrollment: 5
Sex: ALL
Maximum age (years): 47
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 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.

Primary outcomes:
measure: Incidence of transplant related mortality
timeFrame: Up to 100 days post treatment
measure: Incidence of transplant related mortality
timeFrame: At 6 months post treatment
measure: Transgene copy number on peripheral blood mononuclear cells (PBMCs)
timeFrame: Up to 15 years post treatment
measure: Transgene copy number on sorted cell populations
timeFrame: Up to 15 years post treatment
measure: Detection of replication-competent lentivirus (RCL)
timeFrame: 3 months post treatment
measure: Absence of any severe adverse events due to insertional mutagenesis
timeFrame: Up to 15 years post treatment
measure: Change in Artemis mRNA levels
timeFrame: At Day 0, 12 months and 24 months post treatment
measure: Adverse events
timeFrame: Up to 15 years post treatment
measure: Transgene copy number in the transduced CD34+ cells in the drug substance
timeFrame: At Day 0
measure: Change in total number of T cells
timeFrame: 6, 12, 24 months post treatment
measure: Change in distribution of different subpopulations
timeFrame: 6, 12, 24 months post treatment
measure: Change in T lymphocyte in vitro proliferation in the presence of mitogens and antigens
timeFrame: 6, 12, 24 months post treatment
measure: Change in repertoire of T lymphocytes
timeFrame: 12, 24 months post treatment
measure: Evaluation of the B lymphocyte compartment
timeFrame: 6 months post treatment
measure: Evaluation of the B lymphocyte compartment
timeFrame: At 12 months post treatment
measure: Evaluation of the B lymphocyte compartment
timeFrame: At 24 months post treatment
Secondary outcomes:
measure: End of ongoing infection before the transplantation
timeFrame: Up to 15 years post treatment
measure: Kinetics of immune reconstitution
timeFrame: Up to 15 years post treatment
measure: Adverse event
timeFrame: Up to 15 years post treatment
Other outcomes:
Locations:
city: Paris
country: France
facility: Department of Pediatric Immunology, Hematology and Rheumatology UIHR, Necker-Enfants Malades Hospital
Study officials:
affiliation: Department of Biotherapy,LTCG, Necker-Enfants Malades Hospital
name: Alessandra MAGNANI, MD, PhD
role: STUDY_DIRECTOR
affiliation: IMAGINE
name: Chantal Lagresle-Peyrou, MD
role: STUDY_DIRECTOR
References: