What side effects are associated with this type of intervention?

Common treatments for IPEX Syndrome include immunosuppressive therapies like cyclosporine and biologics. Cyclosporine can induce hair growth but is associated with serious adverse effects such as liver enzyme elevation, pancreatitis, and bone marrow suppression, which often preclude long-term use. Biologics targeting immune pathways, such as anti-IL-17 monoclonal antibodies, may cause mild to moderate side effects like fever, rash, and itching. These treatments aim to modulate the immune system to reduce autoimmune activity, similar to the approach of enhancing regulatory T cell function in the CD4^LVFOXP3 trial.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for IPEX Syndrome that involve genetically modified CD4+ T cells expressing FOXP3. The current standard treatments for IPEX Syndrome primarily include immunosuppressive therapies and hematopoietic stem cell transplantation. The ongoing Phase 1 clinical trial for CD4^LVFOXP3 represents an investigational approach aiming to enhance regulatory T cell function, which could potentially offer a new therapeutic avenue for this condition.

What other types of research exist?

Promising novel alternatives to CD4^LVFOXP3 for IPEX Syndrome patients include gene therapy approaches, such as the use of viral vectors to deliver functional genes, and protein replacement therapies that aim to correct the underlying genetic defects. Additionally, therapies involving the modulation of immune responses, such as the use of specific cytokine inhibitors or immune checkpoint inhibitors, may also offer potential benefits.

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CAR T-cell Therapy

CD4^LVFOXP3 for IPEX Syndrome

Q: What is the mechanism of action of this treatment?

The most common treatments for IPEX Syndrome focus on enhancing regulatory T cell function, as these cells play a critical role in maintaining immune tolerance and preventing autoimmunity. The trial CD4^LVFOXP3 involves genetically modified CD4+ T cells that express FOXP3, a key transcription factor essential for the development and function of regulatory T cells. By boosting the number and function of these cells, the treatment aims to correct the underlying immune dysregulation in IPEX Syndrome patients, thereby reducing the severity of autoimmune manifestations and improving overall disease management.

Phase 1

Recruiting

Led By Jessie Alexander, MD

Research Sponsored by Bacchetta, Rosa, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

≥ 50% Performance rating on Lansky/Karnofsky Scale

Body weight greater than 8 kg, unless assessed as able to tolerate leukapheresis

Must not have

Eligible for an HLA matched sibling or matched unrelated donor blood stem cell transplant, and be willing to undergo transplant

Inability to meet limits for steroid dosing

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 15 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if using special immune cells can help patients with a rare immune disorder by replacing their faulty immune cells, aiming to restore immune balance and improve health.

Who is the study for?

This trial is for individuals with IPEX Syndrome who have persistent symptoms despite medication, weigh over 8 kg, and can tolerate leukapheresis. Participants should have a FOXP3 gene mutation and be at least 50% functional on the Lansky/Karnofsky Scale. They cannot join if they have severe unrelated diseases, allergies to study treatments, certain cancer histories, are medically unstable or expected to live less than six months.

What is being tested?

The trial is testing CD4^LVFOXP3 in people with IPEX Syndrome to see if it's safe and how it affects their disease. It's a Phase 1 trial focused on evaluating the manufacturing feasibility of this treatment and its administration safety in up to 36 participants.

What are the potential side effects?

Since this is a first-in-human study of CD4^LVFOXP3 for IPEX Syndrome patients, specific side effects are not yet known but will be closely monitored due to the potential risks associated with new experimental therapies.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can do most activities but may need help.

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I weigh more than 8 kg or am considered able to undergo a specific blood filtering procedure.

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I have recurring IPEX symptoms and need medication, even after a stem cell transplant.

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I do not have any current infections.

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My condition involves a FOXP3 gene mutation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am eligible and willing to undergo a stem cell transplant from a matched donor.

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I cannot take the required dose of steroids.

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I have no heart, kidney, lung, liver, or blood diseases unrelated to my cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 15 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 15 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 15 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Find the safe maximum tolerated dose

Meet target cell number for dose manufacturing

Secondary study objectives

Change in Autoantibody Profile

Change in Body Mass Index (BMI)

Change in Creatinine as a measure of Kidney Function

+17 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Cohort B (<12 years)Experimental Treatment1 Intervention

Participants in Cohort B will always follow treatment of participants in Cohort A for the same dose level. Cohort B will start at Dose Level 2 and be administered 3 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If there is no toxicity observed in any participants in Dose Level 2, participants will be enrolled into Dose Level 3 and administered 10 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If in any dose level 1 of 2 participants show toxicity, that dose level will be expanded to 6 participants.

Group II: Cohort A (≥12 years)Experimental Treatment1 Intervention

The first participant in Dose Level 1 will be administered 1.0 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If there is no toxicity observed in the first participant, the following participants in Dose Level 1 will be administered the same dose of 1.0 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If there is no toxicity observed in any participants in Dose Level 1, participants will be enrolled into Dose Level 2 and administered 3 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If there is no toxicity observed in any participants in Dose Level 2, participants will be enrolled into Dose Level 3 and administered 10 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If in any dose level 1 of 2 participants show toxicity, that dose level will be expanded to 6 participants.

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for IPEX Syndrome focus on enhancing regulatory T cell function, as these cells play a critical role in maintaining immune tolerance and preventing autoimmunity. The trial CD4^LVFOXP3 involves genetically modified CD4+ T cells that express FOXP3, a key transcription factor essential for the development and function of regulatory T cells. By boosting the number and function of these cells, the treatment aims to correct the underlying immune dysregulation in IPEX Syndrome patients, thereby reducing the severity of autoimmune manifestations and improving overall disease management.