Ongoing Clinical Trials for Combined Immunodeficiency
This article provides information about 2 ongoing clinical trials investigating gene therapy treatments for combined immunodeficiency. These studies focus on rare genetic forms of the disease caused by defects in specific genes (RAG1 and Artemis) and are being conducted in several European countries including France, Italy, the Netherlands, Poland, and Spain.
Clinical trial locations
- France
- Italy
- Netherlands
- Poland
- Spain
Study on Gene Therapy for Patients with RAG1-Deficient Severe Combined Immunodeficiency Using RAG1-LV-CD34+ Cells
This clinical trial is testing a new gene therapy approach for infants and young children with a rare and severe form of immune system disorder caused by defects in the RAG1 gene. The study is taking place across multiple countries including the Netherlands, Italy, Poland, and Spain.
Who can participate:
This trial is designed for very young patients with specific criteria. Eligible participants must have RAG1-deficient severe combined immunodeficiency confirmed through genetic testing. The child must have very low levels of T cells in their blood—specifically fewer than 300 T cells per microliter, or less than 1 naïve T cell per microliter. The patient must be younger than 2 years old and at least 8 weeks old by the time they receive the preparatory medications. Additionally, there must be no available tissue-matched donor from a sibling or unrelated person who could provide a standard bone marrow transplant. Parents or guardians must provide informed consent, and families must be able to return for follow-up visits over a 2-year period and participate in a 15-year long-term review.
Who cannot participate:
The trial excludes patients who do not have a genetic defect in the RAG1 gene or who do not have severe combined immunodeficiency.
What the trial involves:
This study focuses on evaluating the safety and feasibility of a gene therapy treatment using the patient’s own blood stem cells. The stem cells are collected and then genetically modified in a laboratory to correct the RAG1 defect using a lentiviral vector. Before receiving the modified cells, patients undergo a preparatory treatment with medications called busulfan and fludarabine. The corrected cells are then infused back into the patient’s bloodstream. Researchers will closely monitor participants to assess how well the immune system recovers, track overall health and survival, and watch for any potential side effects. The study includes long-term follow-up for up to 15 years to gather comprehensive data on the treatment’s long-term effects and benefits.
Investigational treatment:
The treatment being tested is called Autologous Hematopoietic Stem Cell Gene Therapy. It uses the patient’s own stem cells that have been modified to carry a corrected version of the RAG1 gene, which is then returned to the body to help restore immune system function.
Study on Gene Therapy for Severe Combined Immunodeficiency (SCID) Using ARTEGENE in Patients with Artemis Gene Mutations
This clinical trial is investigating a gene therapy treatment called ARTEGENE for infants and young children with severe combined immunodeficiency caused by mutations in the Artemis gene (also known as DCLRE1C). The study is being conducted in France.
Who can participate:
Patients eligible for this trial must be up to 47 months (just under 4 years) of age and have a confirmed diagnosis of severe combined immunodeficiency with biallelic mutations in the Artemis gene—this includes cases where there is some remaining gene activity. There must be no genetically matched donor available from a sibling, or no compatible unrelated donor available quickly within six weeks of diagnosis. The trial also allows participation for patients who cannot wait for a donor due to life-threatening infections such as serious viral respiratory infections, CMV infection, adenovirus infection, disseminated BCGitis, or other severe infections. The patient must be covered by a social security scheme, and parents or guardians must sign an informed consent form agreeing to participate after understanding the study details and risks.
What the trial involves:
This Phase 1/2 study evaluates the safety and effectiveness of ARTEGENE gene therapy. The process begins with collecting the patient’s own stem cells through a mobilization procedure. These cells are then modified outside the body using a lentiviral vector to introduce a functional copy of the DCLRE1C gene. Before transplantation, patients receive a conditioning regimen to prepare the body for the modified cells. The ARTEGENE treatment is given as a single dose through an intravenous injection. After transplantation, patients are closely monitored to assess how well the treatment works in restoring immune function, clearing ongoing infections, and reconstituting the immune system. The study also carefully tracks any side effects using standardized safety measures.
Investigational treatment:
ARTEGENE is a gene therapy product that involves using a lentiviral vector to modify the patient’s own hematopoietic stem cells. The modified cells are then transplanted back into the patient to help correct the genetic defect and improve immune function.
Summary
Both ongoing clinical trials represent innovative approaches to treating severe forms of combined immunodeficiency through gene therapy. These studies target specific genetic defects—RAG1 and Artemis gene mutations—that cause life-threatening immune system problems in very young children. Both trials use similar approaches, modifying the patient’s own stem cells to correct the genetic defect and then returning them to the body.
The RAG1-focused trial has a broader geographic reach, being conducted across four European countries (Netherlands, Italy, Poland, and Spain), while the Artemis-focused trial is currently limited to France. Both studies are designed for infants and young children who lack suitable bone marrow donors, providing a potential treatment option when traditional transplantation is not immediately available.
These trials include long-term follow-up periods to thoroughly assess the safety and effectiveness of gene therapy for these rare conditions, with monitoring extending for many years after treatment. Parents and guardians considering participation should discuss all aspects of these studies with their child’s medical team to understand the potential benefits and risks.
