RecruitingNAINTERVENTIONAL

Phase I/II Clinical Trial Stem Cell Gene Therapy in RAG1-Deficient SCID

This study is testing a new type of gene therapy for very young children (aged 8 weeks to 24 months) who have a serious medical condition called RAG1-deficient SCID. This condition means their immune system doesn't work properly, making them very vulnerable to infections. For these children, traditional bone marrow transplants can be difficult if a suitable donor isn't found. This trial uses the child's own blood cells, which are modified in a lab to include a healthy RAG1 gene, and then given back to the child. The aim is to see if this new treatment works, is safe, and can help restore their immune system. This could offer a new hope for children without matched donors.

At a glance

Status

Recruiting

Phase

Sponsor

Leiden University Medical Center

Enrolment target

Start

23 Jul 2021

Estimated completion

31 Dec 2029

Severe Combined Immunodeficiency Due to RAG1 Deficiency

What is this study about?

Severe Combined Immunodeficiency (SCID), sometimes called 'bubble baby disease', is a very serious condition where a child's immune system doesn't work properly. This means they can't fight off germs and are at high risk of severe, repeated infections. Without treatment, children with SCID often don't survive beyond their first year.

One common type of SCID is caused by a problem with a specific gene called RAG1. For many years, the main and most effective treatment has been a special type of transplant called an allogeneic hematopoietic stem cell transplant (also known as a bone marrow transplant). This involves using healthy immune cells from a donor. However, finding a donor whose cells are a very close match (called HLA-matched) can be difficult, and transplants still carry serious risks, such as the body rejecting the new cells.

This new study is exploring gene therapy as an alternative, particularly for young children with RAG1-deficient SCID who don't have a suitable matched donor. Gene therapy involves taking some of the child's own blood cells, correcting the faulty RAG1 gene in those cells outside the body, and then giving these 'corrected' cells back to the child. The goal is for these corrected cells to grow and produce a working immune system. Researchers have already seen promising results in laboratory studies and with other types of SCID, and this trial aims to see if this approach is safe and effective for RAG1-deficient SCID.

Key takeaways

This study evaluates a new gene therapy for RAG1-deficient SCID.
It's for children aged 8 weeks to 24 months without a matched donor for traditional transplant.
The therapy uses the child's own cells, modified with a healthy RAG1 gene.
Aims to restore the immune system and improve health.
Requires regular follow-up for at least 2 years, with longer-term monitoring.
Participation is voluntary, and you can withdraw at any time.

Who may be eligible?

This study is specifically for very young children, between 8 weeks and 24 months old, who have a severe immune condition called RAG1-deficient Severe Combined Immunodeficiency (SCID).

To be considered, it must be confirmed by genetic tests that your child has RAG1-deficient SCID, and their immune system must show very low levels of certain important cells. A crucial part of eligibility is that your child *does not* have a suitable matched donor for a standard bone marrow transplant. If a matched donor is available, this study will not be an option. Parents or legal guardians will need to provide informed consent, and families must be able to attend regular follow-up appointments at the study centre for at least two years.

There are also some reasons why a child might not be able to join the study. These include having another serious health condition that would make the treatment unsafe, such as severe heart or kidney problems, or being on a ventilator. Children who have already had a bone marrow transplant, or those with other specific syndromes or certain infections (like HIV), would also not be eligible.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Is your child between 8 weeks and 24 months old?
Has your child been diagnosed with RAG1-deficient SCID by genetic testing?
Does your child currently have very low levels of certain immune cells?
Does your child *not* have a suitable matched donor for a standard bone marrow transplant?
Does your child *not* have other serious health problems that would prevent treatment?

Answer every question to see your result.

What does participation involve?

If your child is accepted into the study, the treatment involves several steps. First, some of your child's blood cells will be collected. These cells will then be sent to a special lab where a healthy version of the RAG1 gene will be carefully inserted into them. While these cells are being prepared, your child will receive some medication to help prepare their body to accept the new, corrected cells. Once the gene-corrected cells are ready, they will be given back to your child through an infusion, similar to a blood transfusion.

After the treatment, your child will need to attend regular follow-up appointments at the study centre. These visits will involve various tests and checks to monitor their health, see how well the new cells are working, and ensure the treatment is safe. These follow-up appointments will continue for a period of at least two years after the treatment, with ongoing monitoring for up to 15 years. The research team will explain all the details of the visits, assessments, and the overall duration of the study.

Potential risks and benefits

Participating in this study offers the potential benefit of a new treatment option for RAG1-deficient SCID, especially for children who do not have a matched donor for a standard transplant. If successful, this gene therapy could help restore your child's immune system, allowing them to fight infections and lead a healthier life. However, as with any new treatment, there are potential risks. These can include side effects from the preparatory medication, risks associated with the cell collection and infusion procedures, and potential, though rare, long-term concerns related to the gene therapy itself. The research team will fully discuss all known and potential risks with you. You have the right to withdraw your child from the study at any time, for any reason, without it affecting their ongoing medical care.

Locations (7)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

The Royal Childrens Hospital
Verified postcode
Melbourne, Australia· Not yet recruiting
Ospedale Pediatrico Bambino Gesù
Verified postcode
Roma, Italy· Not yet recruiting
Leiden University Medical Center
Verified postcode
Leiden, Netherlands· Recruiting
Wroclaw Medical University
Verified postcode
Wroclaw, Poland· Recruiting
Hospital Universitari Vall d'Hebron
Verified postcode
Barcelona, Spain· Recruiting
Erciyes Üniversitesi TIP Fakültesi
Verified postcode
Kayseri, Turkey (Türkiye)· Recruiting
University College London Great Ormond Street
Verified postcode
London, United Kingdom· Not yet recruiting

Common questions

What is RAG1-deficient SCID?

It's a serious inherited condition where a child's immune system doesn't work properly, making them very susceptible to infections.

Who is this study for?

It's for babies and toddlers (8 weeks to 24 months old) with RAG1-deficient SCID who cannot find a suitable donor for a standard bone marrow transplant.

What does gene therapy involve?

It involves taking your child's own blood cells, adding a healthy RAG1 gene to them in the lab, and then giving these corrected cells back to your child.

How long will my child be monitored?

Your child will be closely monitored for at least 2 years after the treatment, with long-term follow-up continuing for up to 15 years.

Can I withdraw my child from the study?

Yes, you have the right to withdraw your child from the study at any time, and this will not affect their medical care.

How to find out more

Arjan C Lankester, Prof. Dr.

A.Lankester@lumc.nl 0031715264871 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.