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Autologous Cd34+ Haematopoietic Stem And Progenitor Cells Transduced With A Lentiviral Vector Containing The Human Dclre1C Gene

This article discusses a Phase 1/2 clinical trial investigating the use of ARTEGENE, a gene therapy drug for treating Severe Combined Immunodeficiency (SCID) caused by mutations in the Artemis gene. The study aims to evaluate the safety and effectiveness of this innovative treatment approach for young patients with this rare and severe immune disorder.

Table of Contents

What is ARTEGENE?

ARTEGENE is an innovative gene therapy drug designed to treat a specific type of Severe Combined Immunodeficiency (SCID). It is currently being studied in a Phase 1/2 clinical trial[1]. ARTEGENE is also known by its scientific name: autologous CD34+ haematopoietic stem and progenitor cells transduced with a lentiviral vector containing the human DCLRE1C gene.

How Does ARTEGENE Work?

ARTEGENE works by using the patient’s own stem cells, specifically CD34+ haematopoietic stem and progenitor cells. These cells are taken from the patient and then modified in a laboratory using a special virus called a lentivirus. This virus carries a healthy copy of the DCLRE1C gene, also known as the Artemis gene, into the cells[1].

Once the cells have been modified, they are given back to the patient through an intravenous injection. The modified cells can then produce healthy immune cells, potentially correcting the immune system deficiency[1].

Medical Condition Treated

ARTEGENE is being developed to treat Severe Combined Immunodeficiency (SCID) caused by biallelic mutations in the Artemis gene (DCLRE1C)[1]. SCID is a rare genetic disorder that severely affects the immune system, making patients extremely vulnerable to infections. The specific type of SCID treated by ARTEGENE is caused by mutations in the Artemis gene, which is crucial for the development of immune cells.

Clinical Trial Objectives

The main objective of the ARTEGENE clinical trial is to assess the initial safety and efficacy of the treatment. This includes evaluating the entire process from mobilization of stem cells to conditioning and transplantation of the modified cells[1].

Secondary objectives include:

  • Studying how well the treatment clears ongoing infections present before transplantation[1]
  • Evaluating the functional performance of the new lentiviral vector used in the therapy[1]
  • Assessing the long-term safety and efficacy of ARTEGENE[1]

Eligibility Criteria

To be eligible for the ARTEGENE clinical trial, patients must meet certain criteria:

Inclusion Criteria:

  • Age up to 47 months[1]
  • Confirmed SCID with biallelic mutations in the Artemis (DCLRE1C) gene[1]
  • No available HLA-identical donor or compatible unrelated donor within six weeks of diagnosis[1]
  • Presence of life-threatening infections that require immediate treatment[1]

Exclusion Criteria:

  • Unwillingness to return for follow-up during the first 2 years and long-term follow-up[1]
  • HIV-1, HIV-2, or HTLV1 infections[1]
  • Hypersensitivity to certain medications used in the treatment process[1]
  • Inability to tolerate procedures necessary for the treatment[1]

Treatment Process

The ARTEGENE treatment process involves several steps:

  1. Stem Cell Collection: The patient’s own stem cells are collected through a process called apheresis or bone marrow harvest[1].
  2. Gene Modification: The collected stem cells are modified in a laboratory using a lentivirus carrying the healthy DCLRE1C gene[1].
  3. Conditioning: The patient receives medications to prepare their body for the transplant[1].
  4. Transplantation: The modified stem cells are given back to the patient through an intravenous injection[1].
  5. Follow-up: The patient is monitored closely for safety and efficacy of the treatment[1].

Safety and Efficacy

The primary focus of the ARTEGENE clinical trial is to assess the safety and efficacy of the treatment. Researchers will be monitoring for any adverse events using a standardized scale called CTCAE (Common Terminology Criteria for Adverse Events)[1].

The efficacy of the treatment will be evaluated by observing:

  • The clearance of ongoing infections present before the transplantation[1]
  • The kinetics of immune reconstitution, which means how quickly and effectively the immune system rebuilds itself[1]

It’s important to note that as ARTEGENE is still in clinical trials, its long-term safety and efficacy are yet to be fully determined. Patients and their families should discuss all potential risks and benefits with their healthcare providers.

Aspect Details
Study Type Phase 1/2, open-label, non-randomized, multicentric, single-arm
Condition Severe Combined Immunodeficiency (SCID) caused by Artemis gene mutations
Treatment ARTEGENE (autologous CD34+ cells modified with DCLRE1C gene)
Primary Objective Assess safety and efficacy of ARTEGENE treatment
Key Eligibility Patients up to 47 months old with confirmed SCID due to Artemis mutations
Administration Single intravenous injection of modified stem cells
Follow-up 2 years initial study period with long-term follow-up

FAQ

  • What is ARTEGENE and how does it work? ARTEGENE is a gene therapy drug that uses the patient's own modified stem cells to treat SCID caused by Artemis gene mutations. It involves collecting the patient's blood stem cells, modifying them with a correct copy of the DCLRE1C gene, and then returning them to the patient to help rebuild a functioning immune system.
  • Who is eligible for this clinical trial? The trial is open to patients up to 47 months of age with confirmed SCID due to Artemis gene mutations. Patients must lack a suitable donor for stem cell transplant or face life-threatening infections that require immediate treatment.
  • What are the main goals of this clinical trial? The primary goal is to assess the initial safety and efficacy of ARTEGENE, including the procedures for collecting and modifying stem cells, as well as the transplantation process. Secondary objectives include studying the clearance of existing infections and evaluating the long-term safety and effectiveness of the treatment.
  • How is the gene therapy administered? The gene therapy is administered through a single intravenous injection of the modified stem cells (ARTEGENE drug product). Before the treatment, patients undergo a process to collect their stem cells and receive conditioning medication to prepare their body for the therapy.
  • What kind of follow-up care is required after the treatment? Patients are required to return for follow-up visits during the first two years of the study and participate in long-term follow-up care. This allows researchers to monitor the patients' progress, immune system reconstitution, and any potential side effects or complications from the treatment.

Ongoing Clinical Trials on Autologous Cd34+ Haematopoietic Stem And Progenitor Cells Transduced With A Lentiviral Vector Containing The Human Dclre1C Gene

  • Study on Gene Therapy for Severe Combined Immunodeficiency (SCID) Using ARTEGENE in Patients with Artemis Gene Mutations

    Recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    France

Glossary

  • Severe Combined Immunodeficiency (SCID): A group of rare genetic disorders characterized by little or no immune system function, leaving patients highly susceptible to infections.
  • Artemis gene (DCLRE1C): A gene responsible for producing a protein important in DNA repair and immune cell development. Mutations in this gene can cause a form of SCID.
  • Autologous: Referring to cells or tissues obtained from the same individual. In this context, it means using the patient's own stem cells for treatment.
  • CD34+ cells: A type of stem cell found in bone marrow and blood that can develop into various types of blood cells, including immune cells.
  • Lentiviral vector: A modified virus used to deliver genetic material into cells, in this case, to introduce the correct DCLRE1C gene into the patient's stem cells.
  • Gene therapy: A treatment approach that involves modifying or replacing faulty genes to treat or prevent disease.
  • HLA-compatible donor: A person whose human leukocyte antigens (HLA) closely match those of the patient, making them suitable for stem cell transplantation.
  • G-CSF: Granulocyte Colony-Stimulating Factor, a medication used to stimulate the production and release of stem cells from the bone marrow.
  • Busulfan and Fludarabine: Medications used in the conditioning regimen to prepare the patient's body for stem cell transplantation.
  • CTCAE: Common Terminology Criteria for Adverse Events, a standardized system for classifying the severity of side effects in clinical trials.

References

  1. http://clinicaltrials.eu/trial/study-on-gene-therapy-for-severe-combined-immunodeficiency-scid-using-artegene-in-patients-with-artemis-gene-mutations/