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NCT Number: 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)

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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Key information

Conditions

Artemis (DCLRE1C ) Deficient Severe Combined Immunodeficiency Congenital, Hereditary, and Neonatal Diseases and Abnormalities DNA Repair-Deficiency Disorders Genetic Diseases, Inborn Immune System Diseases Immunologic Deficiency Syndromes Infant, Newborn, Diseases Metabolic Diseases Nutritional and Metabolic Diseases Primary Immunodeficiency Diseases Severe Combined Immunodeficiency Severe combined immunodeficiency with sensitivity to ionizing radiation Xeroderma Pigmentosum, Complementation Group F

Age range

Up to 47 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Department of Pediatric Immunology, Hematology and Rheumatology UIHR, Necker-Enfants Malades Hospital

Paris, 75015, France

Location status: Recruiting

Location contact

Despina MOSHOUS, MD, PhD

CONTACT

[email protected]

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ARTEGENE drug product

Genetic

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

Primary outcomes

  1. Incidence of transplant related mortality

    Time frame: Up to 100 days post treatment

  2. Incidence of transplant related mortality

    Time frame: At 6 months post treatment

  3. Transgene copy number on peripheral blood mononuclear cells (PBMCs)

    Time frame: Up to 15 years post treatment

    by qPCR

  4. Transgene copy number on sorted cell populations

    Time frame: Up to 15 years post treatment

    Determined on sorted cell populations CD15+,CD14+, CD19+, CD56+ and CD3+ T lymphocytes by qPCR

  5. Detection of replication-competent lentivirus (RCL)

    Time frame: 3 months post treatment

  6. Absence of any severe adverse events due to insertional mutagenesis

    Time frame: Up to 15 years post treatment

  7. Change in Artemis mRNA levels

    Time frame: 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)

  8. Adverse events

    Time frame: Up to 15 years post treatment

    Frequency and severity of clinical AEs and changes in laboratory parameters

  9. Transgene copy number in the transduced CD34+ cells in the drug substance

    Time frame: At Day 0

    by qPCR

  10. Change in total number of T cells

    Time frame: 6, 12, 24 months post treatment

    by flow cytometry

  11. Change in distribution of different subpopulations

    Time frame: 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

  12. Change in T lymphocyte in vitro proliferation in the presence of mitogens and antigens

    Time frame: 6, 12, 24 months post treatment

  13. Change in repertoire of T lymphocytes

    Time frame: 12, 24 months post treatment

    via high-throughput sequencing of the TCR

  14. Evaluation of the B lymphocyte compartment

    Time frame: 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)

  15. Evaluation of the B lymphocyte compartment

    Time frame: 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)

  16. Evaluation of the B lymphocyte compartment

    Time frame: 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)

Secondary outcomes

  1. End of ongoing infection before the transplantation

    Time frame: Up to 15 years post treatment

  2. Kinetics of immune reconstitution

    Time frame: Up to 15 years post treatment

    Kinetics of immune reconstitution

  3. Adverse event

    Time frame: Up to 15 years post treatment

    Adverse event will be measured using CTCAE

Study contacts

Contact information is provided by the study sponsor or research team.

Jinmi BAEK, Master

CONTACT

[email protected]

+33 1 42 19 28 49

Marina CAVAZZANA, MD, PhD

CONTACT

[email protected]

+33 144495068

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Collaborators

  • URC-CIC Paris Descartes Necker Cochin

Registry information

Official study 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

Acronym: ARTEGENE

Important dates

Study start
2023
Primary completion
2041
Study completion
2041
First posted
Oct 8, 2021
Registry last updated
Mar 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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