Recruiting
Phase 1

CD4^LVFOXP3

Sponsor:

Bacchetta, Rosa, MD

Code:

NCT05241444

Conditions

IPEX

Eligibility Criteria

Sex: Male

Age: 0 - 35

Healthy Volunteers: Not accepted

Interventions

CD4^LVFOXP3

Study Details

Brief summary:

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.

Conditions

IPEX

Study ID

NCT05241444

Start date

Mar 22, 2022

Status verified date

May, 2025

Completion date

Feb, 2037

Anticipated

Primary completion date

Feb, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 0 - 35

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

30 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort A (≥12 years)

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.

experimental: Cohort B (<12 years)

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.

Interventions

CD4^LVFOXP3

Infusion of autologous CD4+ T cells that have undergone lentiviral-mediated gene transfer of:

i) healthy human FOXP3 gene leading to persistent high FOXP3 expression and acquisition of Treg-like cell function; and ii) human CD271 surface marker gene that allows tracking and quantification of the CD4\^LVFOXP3 in the blood.

Primary outcome measure

  • Meet target cell number for dose manufacturing [ Time Frame: Time at release from manufacturing (by Day 0 [infusion day] for each participant) ]
  • Find the safe maximum tolerated dose [ Time Frame: Up to 60 days post-infusion for each participant ]

Central Contacts and Locations

Central contacts

Rosa Bacchetta, MD

650-498-8369rosab@stanford.edu

Locations

Lucile Packard Children's Hospital

Recruiting

Palo Alto, California, United States, 94305

Contacts

SCGT Clinical Trials Program

DL-SCTIntakeCoordinators@stanfordchildrens.org

Principal Investigator:

Jessie Alexander

More Information

Sponsor

Bacchetta, Rosa, MD

Last update posted

May 22, 2025

Last verified

May, 2025

Keywords

  • Treg cells
  • Regulatory T cells
  • Gene therapy
  • autoimmunity
  • Immune Dysregulation Polyendocrinopathy Enteropathy X-linked
  • FOXP3
  • Lentiviral
  • CD271
  • NGFR
  • immune suppression

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Bacchetta, Rosa, MD on 2025-05-22.