RecruitingPHASE1, PHASE2INTERVENTIONAL

Lentiviral Gene Therapy for p47 AR-CGD

This study is testing a new gene therapy for a rare inherited condition called p47 AR-CGD. People with this condition have a faulty gene, which means their immune system can't properly fight off certain bacteria and fungi, leading to serious infections and inflammation. This therapy aims to correct the problem by introducing a healthy copy of the faulty gene into the patient's blood-forming cells. These 'corrected' cells are then put back into the patient, where they should start making healthy immune cells. This is a Phase 1/2 study, meaning it's an early-stage trial looking at the treatment's safety and whether it works. It's hoped this could be an option for patients who don't have a suitable bone marrow donor.

At a glance

Status

Recruiting

Phase

PHASE1, PHASE2

Sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust

Enrolment target

Start

20 Mar 2023

Estimated completion

01 Apr 2029

P47-Phox, Deficiency of

What is this study about?

Chronic Granulomatous Disease (CGD) is a rare inherited condition where the body's immune system doesn't work quite right. Specifically, certain white blood cells which are usually responsible for 'eating' and destroying harmful germs, can't do their job properly. This is because there's a problem with a special enzyme that helps them make germ-killing substances. In a particular type of CGD called p47 AR-CGD, which affects about 30% of patients, this problem is due to a specific mistake in a gene essential for this enzyme.

While many people with CGD can manage their condition with ongoing antibiotics to prevent infections, some still get very severe, even life-threatening, infections or inflammation. A bone marrow transplant can cure CGD, and it works best when a very close match (like a sibling) is found. However, finding a suitable matched donor isn't always possible, and transplants from unmatched donors carry higher risks. This means there's a real need for other treatment options for these patients.

This study is exploring a gene therapy approach for p47 AR-CGD. It involves taking some of the patient's blood-forming stem cells from their bone marrow. In a special laboratory, a healthy copy of the faulty gene is introduced into these cells using a 'gene carrier' (called a lentiviral vector). After this process, these 'corrected' cells are given back to the patient. The hope is that these new cells will grow and produce healthy immune cells that can then effectively fight off infections, improving the patient's health and reducing severe inflammation.

Key takeaways

It's a gene therapy for a rare immune condition called p47 AR-CGD.
Aims to correct a faulty gene to improve the body's ability to fight germs.
This is an early-stage clinical trial (Phase 1/2) looking at safety and effectiveness.
Could be an option for patients who don't have a suitable bone marrow donor.
Involves collecting and correcting the patient's own blood stem cells.

Who may be eligible?

To be considered for this study, you must have p47 AR-CGD, confirmed by genetic testing, and be older than 23 months. You should also have had at least one serious infection or inflammation that needed hospital treatment, despite your usual medicines. A key requirement is that you haven't been able to find a perfectly matched bone marrow donor after a thorough search.

You cannot participate if you are 23 months old or younger, or if you weigh more than 35 kg. You also can't have certain other infections like HIV, Hepatitis B or C, or some other viruses. We'll also need to check that your blood counts and organ functions (like your heart, liver, and kidneys) are healthy enough for the treatment. Your doctors will do these checks to make sure it's safe for you to take part.

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.

Do you have p47 AR-CGD (confirmed by genetics)?
Are you older than 23 months?
Have you had severe infections or inflammation despite usual treatments?
Have you been unable to find a perfectly matched bone marrow donor?
Do you NOT have HIV, Hepatitis B, Hepatitis C, or certain other active infections?

Answer every question to see your result.

What does participation involve?

If you decide to participate, you will first undergo a full health check to ensure you meet all the study requirements. This will involve blood tests, and potentially imaging or other assessments. The main treatment involves collecting your blood-forming stem cells, which requires a procedure called leukapheresis. These cells will then be sent to a special lab for gene correction. Once the cells are ready, you will receive them back into your body, similar to a blood transfusion. You will have regular follow-up visits, which will include blood tests and other examinations, to monitor your health and how well the treatment is working. The total duration of participation, including follow-up, will be discussed in detail by the study team.

Potential risks and benefits

This is an early-stage study, so the potential benefits are not yet fully known. However, gene therapy holds the promise of providing a long-term solution for p47 AR-CGD, potentially improving your body's ability to fight off infections and reduce inflammation, especially if a matched bone marrow donor isn't available. As with any medical procedure, there are potential risks, including side effects from the cell collection, the gene therapy itself, and the conditioning treatments you might receive beforehand. These will be fully explained by the study team. Remember, your participation is voluntary, and you are free to withdraw from the study at any time without affecting your usual medical care.

Locations (1)

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

Great Ormond Street Hospital
Verified postcode
London, United Kingdom· Recruiting

Common questions

What is p47 AR-CGD?

It's a rare inherited immune condition where the body's immune cells can't properly kill certain germs, leading to serious infections and inflammation.

What is gene therapy?

It's a treatment that aims to correct faulty genes by adding a healthy copy to help the body work correctly.

Is this a new treatment?

Yes, this specific gene therapy for p47 AR-CGD is being tested for the first time in a clinical trial. However, similar gene therapies have been studied for other types of CGD.

Who can join this study?

Patients with confirmed p47 AR-CGD older than 23 months who have had severe infections/inflammation and cannot find a suitable bone marrow donor.

What are the potential benefits?

The hope is that this therapy could help the body fight infections better and reduce inflammation, potentially offering a long-term treatment option.

How to find out more

Karen Oprych

k.gladwin@ucl.ac.uk 0207 7626058 Official trial record

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