Study on Gene Therapy for Patients with RAG1-Deficient Severe Combined Immunodeficiency Using RAG1-LV-CD34+ Cells

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What is this study about?

This clinical trial is focused on a rare genetic disorder known as severe combined immunodeficiency (SCID), specifically caused by a defect in the Recombinase Activating Gene 1 (RAG1). SCID is a condition where the immune system is severely weakened, making it difficult for the body to fight off infections. The study is testing a new treatment called RAG1-LV-CD34+ cells, which involves using a patient’s own blood stem cells that have been genetically modified to correct the RAG1 defect. These modified cells are then given back to the patient through an infusion, which is a way of delivering the treatment directly into the bloodstream.

The purpose of the study is to see if this gene therapy is safe and feasible for patients with RAG1-deficient SCID. Participants in the study will receive the gene therapy and will be monitored closely to ensure their safety and to observe how well the treatment works. The study will look at various outcomes, such as the ability of the immune system to recover and function properly, the overall health and survival of the participants, and any potential side effects that may occur.

Throughout the study, researchers will track the participants’ progress over time, including their immune system’s response to the treatment and any changes in their health. The study aims to provide valuable information on the potential of this gene therapy to improve the lives of individuals with RAG1-deficient SCID. Participants will be followed for a period of time to gather comprehensive data on the long-term effects and benefits of the treatment.

1 initial assessment

Eligibility for the trial is confirmed through genetic analysis, ensuring a diagnosis of RAG1-deficient severe combined immunodeficiency (SCID).

Additional criteria include specific blood cell counts, age requirements, and the absence of a suitable donor match.

2 preparation for treatment

The patient undergoes a preparatory regimen, which includes the administration of medications such as busulfan and fludarabine. These medications help prepare the body for the upcoming infusion.

3 infusion of gene-corrected cells

The patient receives an infusion of RAG1-LV-CD34+ cells through an intravenous route. This involves the use of a lentiviral vector to introduce a corrected version of the RAG1 gene into the patient’s own stem cells.

4 monitoring and follow-up

The patient is monitored for safety and effectiveness of the treatment. This includes checking for successful cell generation, overall survival, and any adverse events.

Regular assessments are conducted to evaluate T cell reconstitution, thymic function, and the presence of naive T cells. The patient’s immune system function and quality of life are also monitored.

5 long-term follow-up

The patient continues to be monitored for up to 15 years to assess long-term outcomes, including the rate of infections and overall health status.

Who Can Join the Study?

The patient must have a condition called RAG1-deficient SCID, which is confirmed by a genetic test.
The patient must have a low number of T cells in their blood. T cells are a type of white blood cell important for the immune system. Specifically, they should have less than 300 T cells per microliter of blood, or less than 1 naïve T cell per microliter. Naïve T cells are a type of T cell that has not yet encountered an infection.
The patient must be younger than 2 years old.
The patient must be at least 8 weeks old by the time they receive certain medications called busulfan and fludarabine.
There must be no available HLA-matched donor. This means there is no sibling or unrelated donor who matches the patient’s tissue type perfectly.
The patient’s parent or guardian must sign a form giving permission for the patient to participate in the study. This is called informed consent.
The patient must be able to return to the local center where they received a type of treatment called HSCT (hematopoietic stem cell transplant) for follow-up visits during the 2-year study and for a 15-year long-term review.

Who Cannot Join the Study?

Patients who do not have a genetic defect in the Recombinase Activating Gene 1 (RAG1). This gene is important for the immune system to work properly.
Patients who do not have severe combined immunodeficiency (SCID). This is a condition where the immune system does not work well, making it hard to fight infections.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Uniwersytecki Szpital Kliniczny Im Jana Mikulicza Radeckiego We Wroclawiu	Wroclaw	Poland

Other Sites

Site Name	City	Country
Ospedale Pediatrico Bambino Gesu’	Rome	Italy
Liknd Uryhhtbewubz Mlbeywu Czpvptz (auynf	Leiden	The Netherlands
Hltifrzv Vbja dyznwfue	Barcelona	Spain

Trial status

Country	Status	Recruitment Start
Italy	Not recruiting	11.03.2021
Poland	Recruiting	11.03.2021
Spain	Recruiting	11.03.2021
The Netherlands	Recruiting	11.03.2021

Trial locations

Autologous Hematopoietic Stem Cell Gene Therapy is a treatment that uses a patient’s own stem cells. These stem cells are collected and then modified in a laboratory to correct a genetic defect. In this trial, the stem cells are treated with a special vector that carries a corrected version of the RAG1 gene. After the modification, the stem cells are returned to the patient’s body to help restore their immune system function. This therapy is specifically designed for patients with RAG1-deficient severe combined immunodeficiency (SCID).

Severe Combined Immunodeficiency (SCID) due to RAG1 Deficiency – This is a rare genetic disorder characterized by a severe defect in both the T- and B-lymphocyte systems, which are crucial components of the immune system. The condition arises from mutations in the Recombinase Activating Gene 1 (RAG1), leading to an inability to effectively fight off infections. Infants with this condition often present with recurrent infections, failure to thrive, and other complications due to the lack of functional immune cells. The disease progresses as the immune system remains severely compromised, making affected individuals highly susceptible to infections. Without intervention, the immune deficiency persists, impacting overall health and development.

Trial ID:

2023-510204-50-00

Protocol code:

RAG1

NCT ID:

NCT04797260

Trial Phase:

Human Pharmacology (Phase I) – Other

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Study on Gene Therapy for Patients with RAG1-Deficient Severe Combined Immunodeficiency Using RAG1-LV-CD34+ Cells

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?