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Autologous CD4+ T-Cell Gene Therapy for X-linked Hyper-IgM Syndrome Type 1 in Patients with X-linked Hyper-IgM Syndrome Type 1

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What is this study about?

This clinical trial is studying X-linked immunodeficiency with hyper-IgM type 1 (HIGM1), a rare inherited disease in which the immune system does not work properly and cannot make enough effective antibodies to fight infections. The treatment being tested is FT018, made from the person’s own CD4+ T-cells (a type of white blood cell) that are collected, changed in the laboratory using CRISPR/Cas9 and an IDLV-based vector (a tool used to carry genetic changes into cells), and then given back by intravenous infusion.

The purpose of the study is to evaluate the safety of FT018 in people with HIGM1. The study is open label, which means that both the study team and the participants know which treatment is being given, and it has one treatment group. The treatment course includes one or more infusions of the modified cells, followed by regular follow-up visits over time to watch for side effects, signs of immune system recovery, infections, and overall health. Some participants may receive an additional dose later if needed.

The study also includes several background vaccines used as standard care, including Rabipur, TICOVAC, and Infanrix hexa. These are vaccines against rabies, tick-borne encephalitis, and a group of childhood infections including diphtheria, tetanus, pertussis, hepatitis B, polio, and Haemophilus influenzae type b. The study follows people for up to 2 years after treatment.

1 study treatment with edited cd4+ t-cells

You receive autologous peripheral blood-derived CD4+ t-cells, which are your own cd4+ t-cells (a type of white blood cell) that have been edited outside the body at the cd40lg site using crispr/cas9 and an idlv-based vector.

These cells are given by intravenous infusion (through a vein). The study does not state the dose, frequency, or exact duration of this infusion.

2 follow-up after each dose

After each dose of the study treatment, you are monitored for dose-limiting toxicities (dlt, meaning side effects serious enough to limit the dose that can be given).

The study also checks for adverse events (ae, any unwanted medical problem), serious adverse events (sae, a severe medical problem), adverse events of special interest (aesi, specific side effects the study is watching for), and side effects related to the study treatment.

The study checks for immune reconstitution inflammatory syndrome (iris, a reaction that can happen when the immune system begins to recover and causes inflammation) at 28 days after each dose.

3 possible boost dose

Some patients may receive a boost dose of the study treatment. The study measures the proportion of patients who receive this additional dose.

The source data do not specify the dose, frequency, or timing of the boost dose.

4 long-term follow-up

You are followed after treatment at 6 months, 1 year, and 2 years.

At these time points, the study checks for side effects, including ae, sae, aesi, treatment-related side effects, and iris.

5 infection and survival assessment

The study reviews the number, length, and share of days with moderate to severe infection during the 2 years after treatment.

This review is done in consecutive 6-month periods, including assessments at 6 months, 1 year, 1.5 years, and 2 years.

The study also checks overall survival at 6 months, 1 year, and 2 years after treatment.

6 background vaccines used in the study

The study lists background vaccines given by intramuscular injection (into a muscle). These are rabipur, ticovac 0.25 ml for pediatric use, infanrix hexa, and ticovac 0.5 ml.

Rabipur is a vaccine against rabies (a serious infection that affects the brain and nervous system) and contains inactivated rabies virus. The source data do not provide a dose, frequency, or duration.

Ticovac 0.25 ml for pediatric use is a vaccine against tick-borne encephalitis (a brain infection spread by ticks) and contains inactivated tick-borne encephalitis virus. The source data do not provide a dose, frequency, or duration.

Infanrix hexa is a vaccine against diphtheria, tetanus, whooping cough (pertussis), hepatitis b, polio, and haemophilus influenzae type b (hib, a germ that can cause serious infections). The source data do not provide a dose, frequency, or duration.

Ticovac 0.5 ml is also a vaccine against tick-borne encephalitis and contains inactivated tick-borne encephalitis virus. The source data do not provide a dose, frequency, or duration.

Who Can Join the Study?

  • Signed informed consent is required. This means the patient, or a legal guardian when appropriate, must agree in writing to take part in the study.
  • The patient must be male.
  • The patient must be at least 1 year old.
  • The patient must have a Lansky/Karnofsky score of 80% or higher. This is a measure of how well a person can do normal daily activities and how independent they are.
  • The patient must have a genetic diagnosis of HIGM1. This means the condition has been confirmed by testing the genes.
  • The patient must have absent or reduced CD40L expression or function on CD4+ T-cells after stimulation with PMA/ionomycin. In simple terms, blood cells must show that this protein, called CD40L, is missing or does not work well when tested in the laboratory.
  • The patient must need chronic IgRT. IgRT means immunoglobulin replacement therapy, a regular treatment that gives antibodies to help protect against infections.
  • The patient must show good adherence to IgRT. This means the patient has been able to follow the antibody treatment regularly and as prescribed.

Who Cannot Join the Study?

  • A CD40LG gene change located before the vector insertion site in CD40LG intron 1, or any other gene change that cannot be fixed with the gene-editing treatment.
  • A medical reason that makes vaccination unsafe, if the study protocol requires vaccination, or a medical reason that prevents use of other medicines or procedures planned in the study.
  • Any previous treatment with cell therapy or gene therapy.
  • Positive tests for HIV RNA (human immunodeficiency virus genetic material in the blood), HCV RNA (hepatitis C virus genetic material in the blood), or HBV DNA (hepatitis B virus genetic material in the blood), or the presence of total syphilis antibodies (blood markers showing past or current syphilis infection), if this does not meet the required tissue donation rules for manufacturing.
  • Severe organ dysfunction (poor working of a body organ such as the heart, liver, or kidneys) or another serious illness or medical condition that the study doctor thinks would make the person unsuitable for the study.
  • Previous allogeneic hematopoietic stem cell transplantation (a transplant of blood-forming stem cells from another person) with evidence that some donor cells are still present.
  • Being enrolled in another clinical trial.
  • Not being able to donate enough lymphocytes (a type of white blood cell) to make the study treatment.
  • Using systemic corticosteroids (steroid medicines that work throughout the body) or other immunosuppressive drugs (medicines that lower the immune system) that could interfere with apheresis (a procedure that collects blood cells) or with making the drug product.

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

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Other Sites

Site Name City Country Status
Ospedale San Raffaele S.r.l. Milan Italy

Want to learn more about this study or check if you can participate? Contact us.

Trial status

Country Status Recruitment Start
Italy Italy
Not yet recruiting
01.09.2026

Trial locations

Investigated drugs:

Autologous peripheral blood-derived CD4+ T-cells CRISPR-edited at the CD40LG locus: These are the patient’s own CD4 T-cells, which are a type of white blood cell. They are taken from the blood, changed in the lab using CRISPR gene editing to fix the CD40LG gene area, and then given back by vein. The goal is to help the immune system work better in people with X-linked Hyper IgM syndrome type 1.

Rabipur: This is an inactivated rabies vaccine given by injection into a muscle. It is included as a background vaccine, meaning it is part of the routine care or vaccination history and not the main study treatment.

TICOVAC: This is an inactivated tick-borne encephalitis vaccine given by injection into a muscle. It is included as a background vaccine, meaning it is part of the routine care or vaccination history and not the main study treatment.

Infanrix hexa: This is a combination vaccine that helps protect against diphtheria, tetanus, whooping cough, hepatitis B, polio, and Haemophilus influenzae type b. It is given by injection into a muscle and is listed as background treatment, meaning it is not the main study therapy.

TICOVAC: This is another presentation of the inactivated tick-borne encephalitis vaccine given by injection into a muscle. It is also background treatment and not the main study therapy.

Investigated diseases:

X-linked hyper-IgM syndrome type 1 – A rare inherited immune system disorder caused by a change in the CD40 ligand gene, which affects the normal development of immune defenses. People with this disease have low levels of some protective antibodies and may have higher levels of immunoglobulin M. It usually begins in early childhood and can lead to repeated infections, especially in the lungs, ears, sinuses, and gut. Over time, ongoing immune weakness can cause infections to happen more often and become harder to clear.

Trial ID:
2025-524635-39-00
Trial Phase:
Phase I and Phase II (Integrated) – First administration to humans

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