CD4^LVFOXP3 in Participants With IPEX

NCT05241444 | Recruiting Phase 1 DMC FDA Drug

• 5 other identifiers: IRB-63373DRU-2020-7764RPD-2020-4701R01FD007540-01CLIN2-13259
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Meet target cell number for dose manufacturing

  No more than two products fail the target cell dose and established release criteria.

  Time at release from manufacturing (by Day 0 [infusion day] for each participant)

• Find the safe maximum tolerated dose

  No more than 1 out of 6 participants may experience a related dose limiting toxicity or treatment emergent adverse events.

  Up to 60 days post-infusion for each participant

Secondary Outcomes (31)

• Change in Diarrhea incidence

  Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (daily for the first month followed by monthly at Month 2, 3, 6, 9, 12)

• Change in GI Symptoms - Gastrointestinal Symptoms Rating Scale

  Baseline (up to 60 days before infusion of CD4^LVFOXP3) through post-infusion (Week 4, Month 6, Month 12)

• Change in Body Mass Index (BMI)

  Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 1, 2, 3, Week 1, 2, 3, 4; Month 2, 3, 6, 9, 12)

• Change in age-specific percentiles of height

  Baseline (up to 60 days before infusion of CD4^LVFOXP3) through post-infusion (Month 12)

• Change in age-specific percentiles of bodyweight

  Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 1, 2, 3, Week 1, 2, 3, 4; Month 2, 3, 6, 9, 12)

Study Arms (2)

Cohort A (≥12 years)

EXPERIMENTAL

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.

Biological: CD4^LVFOXP3

Cohort B (<12 years)

EXPERIMENTAL

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.

Biological: CD4^LVFOXP3

Interventions

CD4^LVFOXP3 BIOLOGICAL

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.

Also known as: CD4^LVFOXP3 Treg-like cells

Cohort A (≥12 years); Cohort B (<12 years)

Eligibility Criteria

• Age: 4 Months - 35 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bacchetta, Rosa, MD: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (1)

Lucile Packard Children's Hospital

Palo Alto, California, 94305, United States

RECRUITING

Related Publications (23)

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MeSH Terms

Conditions

Autoimmune Diseases

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Jessie Alexander, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rosa Bacchetta, MD

CONTACT

650-498-8369; rosab@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: Escalating doses of CD4\^LVFOXP3 will be administered in 2-6 participants per dose in two age cohorts (Cohort A: ≥ 12 years of age; Cohort B: \< 12 years of age) using a 2+4 dose escalation design. Cohort B will be started at the second dose level.

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: February 15, 2022
• Study Start: March 22, 2022
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2037
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)