Study Evaluating a Gene Therapy for IPEX Syndrome Through the Expression of FOXP3 on Deficient T Cells to Produce Tregs-like.

NCT07697118 | Not Yet Recruiting Phase 1 DMC

• 2 other identifiers: APHP2511372025-523305-15-00
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of FOXP3-T4 (an autologous gene therapy) alone or in combination with low-dose IL-2 for the treatment of IPEX syndrome. The therapy involves the transplantation of autologous CD4+ T-cells transduced ex vivo with the LV-EF1a-FOXP3-LNGFR lentiviral vector. The study follows a staggered approach: the first two patients will receive FOXP3-T4 monotherapy. Subsequent patients will receive FOXP3-T4 followed if needed by low-dose IL-2 treatment consisting of a daily dose for 5 days, then weekly administrations for 3 months. The study aims to stabilize autoimmune manifestations and potentially cure the underlying disease, ultimately allowing for the discontinuation of ongoing immunosuppressive treatments.

Conditions

The Immune Dysregulation Polyendocrinopathy Enteropathy X-linked Syndrome is a Primary Immunodeficiency Caused by Pathogenic Variants in Forkhead Box Protein 3

Keywords

Autoimmune diseases; Genetic diseases; Gene therapy; Lentiviral vector; Immune dysregulation Polyendocrinopathy Enteropathy X-linked; Autoimmunity-Immunodeficiency Syndrome; Forkhead Box Protein 3; Low-dose IL-2

Outcome Measures

Primary Outcomes (6)

• Frequency of clinical AEs and pathological variations of laboratory parameters

  Number of clinical AEs

  Up to 24 months post-infusion

• Severity of clinical AEs and pathological variations of laboratory parameters

  Grading will be performed according to the CTCAE (Common Terminology Criteria for Adverse Events) current version. Severity is rated on a scale of Grade 1 (Mild) to Grade 5 (Death).

  Up to 24 months post-infusion

• Incidence of clinically detectable lymphoproliferation and abnormal clonal dominance

  This is measured via Vector Insertion Site Analysis (VISA)

  Up to 24 months post-infusion

• Incidence of clinically detectable lymphoproliferation and abnormal clonal dominance

  This is measured by proliferation of LNGFR+ cells

  Beyond 3 months to 24 months post-infusion

• Detection of Replication-Competent Lentivirus (RCL)

  Up to 24 months post-infusion

• Persistence of recirculating LNGFR+among CD4+ T cells

  Percentage of LNGFR+ among CD4+ T cells

  at 3 months post-infusion

Secondary Outcomes (24)

• Persistence of FOXP3-T4 Cells

  Up to 24 months post-infusion

• Phenotyping

  Up to 24 months post-infusion

• Vector Copy Number (VCN) Analysis

  Up to 24 months post-infusion

• Immunophenotyping T and B cells if no change is detected from the baseline (e.g. before treatment), the immunological phenotype

  Beyond 3 months to 24 months post-infusion

• TCR repertoire

  At 3 months, 12 months and 24 months, post-infusion

Study Arms (1)

FOXP3-T4 drug product

EXPERIMENTAL

FOXP3-T4 is a genetically modified cell therapy product consisting of autologous CD4+ T-cells transduced ex vivo with a self-inactivating bidirectional lentiviral vector (LV-EF1a-FOXP3-LNGFR) expressing the FOXP3 and LNGFR cDNAs.

Genetic: FOXP3-T4 drug product; Drug: ILT-101

Interventions

FOXP3-T4 drug product GENETIC

Each patient will receive a single IV infusion of FOXP3-T4, autologous gene-modified CD4+ T-transduced ex vivo with a self-inactivating lentiviral vector (LV-EF1a.FOXP3-LNGFR)

FOXP3-T4 drug product

ILT-101 DRUG

The first two patients included in the study will not receive IL-2 treatment. The others will receive the first injection the FOXP3-T4 treatment and if needed IL2-treatment. For IL2 treatment, patients will receive a daily dose for 5 days, followed by an administration per week for 3 months (ILT-101)

Also known as: Adeleuskin or IL2

FOXP3-T4 drug product

Eligibility Criteria

• Age: 1 Year - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male patients only
• Patients aged from 1 - 45 years of age (the first three patients will be aged between 10 - 45 years of age)
• Patient with IPEX syndrome caused by mutation of the FOXP3 gene
• Patients are eligible from the second line of treatment onward, even those under controlled disease
• Patient with recurrent IPEX symptoms, under immune suppressive medications
• Patient for whom HSCT is not feasible or when no suitable compatible donor is available
• Patients who have had prior allogeneic blood stem cell transplantation (HSCT) with engraftment failure defined as no intake of donor cells
• Patient or parental, guardian's patient signed informed consent
• Male participants of reproductive potential with a partner of childbearing potential (WOCBP): willing to use an effective method of contraception during the trial and for at least 12 months post-infusion
• Affiliation to a French or European social security scheme

You may not qualify if:

• Unwillingness to return for follow-up during the 2-year study and during the 15 years of long term follow up study.
• Patient with short life expectancy
• Patient on AME (state medical aid) (unless exemption from affiliation).
• Diagnosis of a significant psychiatric disorder of the patient that could seriously impede the ability to participate in the study.
• Eligible for an HLA matched sibling or matched unrelated donor blood stem cell transplant (HLA 10/10) and be willing to undergo transplant.
• Patients with uncontrolled or ongoing active infections.
• HIV-1 or 2 or HTLV-1 infections.
• Patients with severe IPEX clinical presentation needing a rapid allogeneic HSCT treatment within 3 months.
• Patients with known history of hypersensitivity to IL-2 or any component of the formulation (mannitol, sodium lauryl sulfate, monosodium phosphate dehydrate, disodium phosphate dehydrate, glucose.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Department of Biotherapy, Hopital Necker Enfants malades

Paris, Île-de-France Region, 75015, France

Location

Related Publications (1)

• Delville M, Bellier F, Leon J, Klifa R, Lizot S, Vincon H, Sobrino S, Thouenon R, Marchal A, Garrigue A, Olivre J, Charbonnier S, Lagresle-Peyrou C, Amendola M, Schambach A, Gross D, Lamarthee B, Benoist C, Zuber J, Andre I, Cavazzana M, Six E. A combination of cyclophosphamide and interleukin-2 allows CD4+ T cells converted to Tregs to control scurfy syndrome. Blood. 2021 Apr 29;137(17):2326-2336. doi: 10.1182/blood.2020009187.

  PMID: 33545713 BACKGROUND

MeSH Terms

Conditions

Autoimmune Diseases; Genetic Diseases, Inborn

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Immune System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Emmanuelle SIX, MD, PhD

  Institut Imagine

  STUDY CHAIR

Central Study Contacts

Marina CAVAZZANA, MD, PhD

CONTACT

01 44 49 50 68; m.cavazzana@aphp.fr

Aline DECHANET, Project Manager

CONTACT

01 44 38 17 11; aline.dechanet@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2026
• First Posted: July 13, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: July 13, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)