Gene Therapy for Hyper IgM Syndrome

Overseen By Suk S De Ravin, M.D.

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Disqualifiers: Allergies, Febrile illness, Alemtuzumab consent, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 5 weeks or more

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy for individuals with X-linked hyper-IgM syndrome, a rare immune disorder that impairs the immune system's ability to fight infections. The trial uses base-edited hematopoietic stem and progenitor cells, along with T cells, to correct the faulty gene causing the disorder. It targets a single male with this specific genetic mutation and involves a one-time treatment followed by regular check-ups for several years. As a Phase 1 trial, the research aims to understand how the treatment works in humans, offering a unique opportunity to be among the first to receive this innovative therapy.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you will need to take certain drugs to prepare your body for the stem cell treatment, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that specially edited blood stem cells could help treat genetic conditions. These cells undergo changes to correct gene issues, such as the CD40L gene problem in hyper-IgM syndrome. In studies for other diseases, like chronic granulomatous disease, these edited cells have generally been safe with few serious side effects.

This trial is in the early stages (Phase 1/2), focusing mainly on safety, so information on long-term effects remains limited. However, the method aims to make precise DNA changes, potentially reducing the risk of unwanted alterations.

While the treatment is still under investigation, similar research has demonstrated promising safety results. Participants can be assured that safety remains a top priority in these trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike standard treatments for Hyper IgM Syndrome, which often involve regular immunoglobulin replacement therapy and antibiotics, this new approach uses base-edited hematopoietic stem and progenitor cells (HSPCs). These cells are genetically modified to potentially correct the underlying genetic defect responsible for the condition. This gene therapy offers a one-time infusion, promising a long-term solution by directly addressing the root cause rather than just managing symptoms. Researchers are excited because this could fundamentally change the way Hyper IgM Syndrome is treated, offering hope for a more permanent and effective solution.

What evidence suggests that this gene therapy could be an effective treatment for Hyper IgM Syndrome?

Studies have shown that specially edited stem cells can address genetic issues like those in CD40L-HIGM syndrome. Research indicates that these cells can restore the CD40 ligand, crucial for a healthy immune system. Patients with conditions similar to X-linked hyper-IgM syndrome have shown immune system improvements after receiving these gene-edited cells. In this trial, participants will receive a one-time infusion of base-edited hematopoietic stem and progenitor cells, following conditioning with busulfan and alemtuzumab. This process involves altering the stem cells to correct the genetic error, enhancing the body's ability to fight infections. Early findings suggest this method could be a promising treatment for individuals with this rare immune disorder. ^{1 3 4 5 6}

Who Is on the Research Team?

Suk S De Ravin, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is specifically for a male with CD40L-Hyper IgM Syndrome, which affects white blood cells and increases the risk of infections and autoimmune diseases. The participant will undergo extensive screening including imaging scans, blood tests, and possibly a bone marrow biopsy.

Inclusion Criteria

Provision of signed and dated informed consent form

Use of condoms or other methods to ensure effective contraception with partner

Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

Unwillingness to submit information as part of the alemtuzumab (Campath(R)) Distribution Program application or deemed unqualified by the Distribution Program committee

Known allergic reactions to components of the BE HSPC study product

I have not had a fever or illness in the last two weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Apheresis and Base Editing

Participant may undergo apheresis to collect stem cells, which will then undergo base editing to repair the mutation.

2-3 weeks

Treatment

Participant will be admitted to the hospital for 5 weeks or more. For 2 weeks, he will receive drugs to prepare his body for receiving the stem cells. After receiving the edited stem cells, he will remain in the hospital until his cell counts recover.

5 weeks or more

Inpatient stay

Follow-up

Participant will have follow-up visits every few months in the first 2 years after treatment. The bone marrow biopsy will be repeated after 2 years.

24 months

Visits every few months

Long-term Follow-up

Long-term visits will continue annually for 15 years.

15 years

Annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Base-edited hematopoietic stem and progenitor cells

Trial Overview The study is testing gene therapy using base-edited stem cells to treat one patient with CD40L-HIGM syndrome. It involves collecting the patient's stem cells, editing them to repair the genetic mutation, then transplanting them back after pre-treatment with drugs in hospital.

How Is the Trial Designed?

Group I: Single Arm Study Experimental Treatment 6 Interventions

The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following conditioning using busulfan and alemtuzumab.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06959771

NCT06959771 | Base Editing Hematopoietic Stem Cell and ... Primary Objective: To determine the safety and efficacy of BE HSPC CD40L and BE T cells. Secondary Objectives: To determine restoration of CD40L expression and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11585743/

Progress toward the challenging goal of HDR-based gene ... This study highlights the optimization of HDR-mediated gene editing as a potential clinical tool for treating XHIM.

3. cell.com cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(24)00113-X

DNA-PK inhibition enhances gene editing efficiency in ... DNA-PK inhibition enhances gene editing efficiency in HSPCs for CRISPR-based treatment of X-linked hyper IgM syndrome.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2211124718307010

Site-Specific Gene Editing of Human Hematopoietic Stem ... X-linked hyper-immunoglobulin M (hyper-IgM) syndrome (XHIM) is a primary immunodeficiency characterized by the absence of IgG, IgA, and IgE with ...

5. withpower.com withpower.com/trial/phase-2-syndrome-4-2025-c938f

Gene Therapy for Hyper IgM Syndrome ... Base-edited hematopoietic stem and progenitor cells will have tolerable side effects & efficacy for patients with Hyper IgM Syndrome. See if you qualify today!

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11753194/

High-fidelity PAMless base editing of hematopoietic stem ... High-fidelity PAMless base editing of hematopoietic stem cells to treat chronic granulomatous disease