CD4^LVFOXP3 in Participants With IPEX

Phase 1 Study of Autologous CD4^LVFOXP3 in Participants With Immune Dysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) Syndrome

This first-in-human, Phase 1 clinical trial will test the feasibility of the manufacturing and the safety of the administration of CD4^LVFOXP3 in up to 30 evaluable human participants with IPEX and evaluate the impact of the CD4^LVFOXP3 infusion on the disease.

Treatment with CD4^LVFOXP3 is expected to replace the defective Treg cells of the participants, and restore control of the immune system and therefore ameliorate symptoms of IPEX.

We expect to learn the following from this study:

1. That CD4^LVFOXP3 can be consistently produced and be of expected quality to be used in humans,
2. That CD4^LVFOXP3 are safe in children and young adults with IPEX, and determine its effects, both good and bad,
3. That CD4^LVFOXP3 can improve overall health and allow reduction of medication/s.

This Phase 1 (feasibility and safety) trial will gather data about CD4^LVFOXP3 in vivo persistency and early signs of impact on symptoms of IPEX.

Inclusion Criteria:

• Body weight greater than 8 kg, unless assessed as able to tolerate leukapheresis
• FOXP3 gene mutation
• Medical history of progressive symptoms of IPEX with persistency of some symptoms and/or signs requiring immune suppressive medication. The participant may or may not be on immunosuppression at time of starting the study.
• Uncontrolled IPEX disease but unable to tolerate immune suppressive medication
• Recurrent IPEX symptoms, requiring immune suppressive medications, in participants who have had prior allogeneic (allo) blood stem cell transplantation (HSCT).
• ≥ 50% Performance rating on Lansky/Karnofsky Scale
• Organ and marrow function within acceptable levels of function
• Absence of ongoing infections
• Must be able to consent if an adult

Exclusion Criteria:

• Medical instability
• Less than 6 months life expectancy
• Inability to meet limits for steroid dosing
• Eligible for an HLA matched sibling or matched unrelated donor blood stem cell transplant, and be willing to undergo transplant.
• Unrelated or comorbid disease
• Allergy to any study medication, product, or intervention
• Currently receiving another experimental treatment
• History of malignancy, unless disease free for at least 2 years, with the exception of non melanoma skin cancer or carcinoma in situ