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

6. juli 2026 oppdatert av: Assistance Publique - Hôpitaux de Paris

A Phase I/II Open-label, Non-randomized, Monocentric, Single-arm Study Evaluating the Safety and Efficacy of Induced CD4+ Treg by LV Vector Transduction Expressing the FOXP3 cDNA (FOXP3-T4) in Patients With IPEX Syndrome

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.

Studieoversikt

Status

Har ikke rekruttert ennå

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

IPEX syndrome is a primary immunodeficiency caused by hemizygous mutations in the gene FOXP3, which encodes an essential transcription factor required to maintain immunological tolerance by thymus-derived regulatory T (Treg) cells. The most common presentation suggestive of the diagnosis of IPEX syndrome is the classical triad of enteropathy, type I diabetes (TID), and eczema in neonatal onset. Still, it is now well established that IPEX syndrome comprises a broad spectrum of clinical manifestations with different degrees of severity and evolution.

Currently, the only curative treatment for the severe form is allogeneic hematopoietic stem cell transplantation (HSCT). However, because of its significant toxicity, it can be proposed only for more severe presentations and when an HLA identical donor is available. Moreover, the post-HSCT prognosis is also linked to prior disease activity and organ failures.

This clinical study aims to assess a new therapeutical strategy consisting of the conversion of the IPEX patient's CD4+T-cells into functional Treg-like cells by transducing them with an optimized bidirectional lentivirus vector expressing human FOXP3 and a truncated form of the low-affinity nerve growth factor receptor (ΔLNGFR) allowing the selection of the transduced cells. To favour Treg-like cells engraftment and expansion, the FOXP3-T4 infusion may be combined with subcutaneous injection of low-dose IL-2, if needed. Injecting FOXP3-T4 T-reg-like cells into IPEX patients is expected to stably improve the autoimmune manifestations and even cure the underlying disease, allowing the ongoing immunosuppressive treatments to be stopped.

Studietype

Intervensjonell

Registrering (Antatt)

5

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

  • Navn: Marina CAVAZZANA, MD, PhD
  • Telefonnummer: + 33 01 44 49 50 68
  • E-post: m.cavazzana@aphp.fr

Studer Kontakt Backup

Studiesteder

  • Frankrike
    • Île-de-France Region
      • Paris, Île-de-France Region, Frankrike, 75015
        • Department of Biotherapy, Hopital Necker Enfants malades
        • Ta kontakt med:

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Barn
  • Voksen

Tar imot friske frivillige

Nei

Beskrivelse

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: FOXP3-T4 drug product
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.
Genetisk: FOXP3-T4 drug product
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)
Legemiddel: ILT-101
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)
Andre navn:
  • Adeleuskin or IL2

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Frequency of clinical AEs and pathological variations of laboratory parameters
Tidsramme: Up to 24 months post-infusion
Number of clinical AEs
Up to 24 months post-infusion
Severity of clinical AEs and pathological variations of laboratory parameters
Tidsramme: Up to 24 months post-infusion
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
Tidsramme: Up to 24 months post-infusion
This is measured via Vector Insertion Site Analysis (VISA)
Up to 24 months post-infusion
Incidence of clinically detectable lymphoproliferation and abnormal clonal dominance
Tidsramme: Beyond 3 months to 24 months post-infusion
This is measured by proliferation of LNGFR+ cells
Beyond 3 months to 24 months post-infusion
Detection of Replication-Competent Lentivirus (RCL)
Tidsramme: Up to 24 months post-infusion
Up to 24 months post-infusion
Persistence of recirculating LNGFR+among CD4+ T cells
Tidsramme: at 3 months post-infusion
Percentage of LNGFR+ among CD4+ T cells
at 3 months post-infusion

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Persistence of FOXP3-T4 Cells
Tidsramme: Up to 24 months post-infusion
Persistence of recirculating LNGFR among CD4+ T cells
Up to 24 months post-infusion
Phenotyping
Tidsramme: Up to 24 months post-infusion
Deeper phenotyping of FOXP3-T4 (CD4+LNGFR+ CD25+ FOXP3+ CD127low)
Up to 24 months post-infusion
Vector Copy Number (VCN) Analysis
Tidsramme: Up to 24 months post-infusion
Quantification of the transgene copy number (VCN) on drug product and on sorted T-CD4+
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
Tidsramme: Beyond 3 months to 24 months post-infusion
Beyond 3 months to 24 months post-infusion
TCR repertoire
Tidsramme: At 3 months, 12 months and 24 months, post-infusion
Evaluated by NGS before and after the treatment with FOXP3-T4
At 3 months, 12 months and 24 months, post-infusion
Autoantibodies dosage
Tidsramme: At 3 months, 6 months, 12 months and 24 months post-infusion
At 3 months, 6 months, 12 months and 24 months post-infusion
Organ-Specific Remission: Skin disease
Tidsramme: Up to 24 months post-infusion
Diminution of the skin lesions severity
Up to 24 months post-infusion
Organ-Specific Remission: Skin disease
Tidsramme: Up to 24 months post-infusion
Diminution of inflammation in the skin biopsy
Up to 24 months post-infusion
Organ-Specific Remission: Endocrine System Function
Tidsramme: Up to 24 months post-infusion
Evaluation of the functions of endocrine glands
Up to 24 months post-infusion
Organ-Specific Remission: Endocrine System Function
Tidsramme: Up to 24 months post-infusion
Reduction of insulin dose administrered
Up to 24 months post-infusion
Organ-Specific Remission: Endocrine System Function
Tidsramme: Up to 24 months post-infusion
Reduction of HBA1C
Up to 24 months post-infusion
Organ-Specific Remission: Renal function
Tidsramme: Up to 24 months post-infusion months
Improvement of creatine and creatine clearance
Up to 24 months post-infusion months
Organ-Specific Remission: Renal function
Tidsramme: Up to 24 months post-infusion months
Improvement of proteinuria
Up to 24 months post-infusion months
Organ-Specific Remission: Renal function
Tidsramme: Up to 24 months post-infusion months
Improvement of tubular effect
Up to 24 months post-infusion months
Organ-Specific Remission: Digestive System
Tidsramme: Up to 24 months post-infusion months
Change in the weight curve
Up to 24 months post-infusion months
Organ-Specific Remission: Digestive System
Tidsramme: Up to 24 months post-infusion months
Change in diarrhea incidence
Up to 24 months post-infusion months
Organ-Specific Remission: Digestive System
Tidsramme: Up to 24 months post-infusion months
Decrease of fecal calprotectin
Up to 24 months post-infusion months
Organ-Specific Remission: Musculoskeletal System
Tidsramme: Up to 24 months post-infusion months
Improvement of arthritis evaluated by physical examination
Up to 24 months post-infusion months
Organ-Specific Remission: Respiratory Function
Tidsramme: Up to 24 months post-infusion months
Improvement of asthma evaluated by physical examination
Up to 24 months post-infusion months
Organ-Specific Remission: General status
Tidsramme: Up to 24 months post-infusion months
Improvement of performance status : Lansky and Karnofsky scores range from 100 to 10
Up to 24 months post-infusion months
Organ-Specific Remission: Blood count
Tidsramme: Up to 24 months post-infusion months
Presence of autoimmune hemolytic anemia
Up to 24 months post-infusion months
Organ-Specific Remission: Blood count
Tidsramme: Up to 24 months post-infusion months
Presence of thrombocytopenia
Up to 24 months post-infusion months
Organ-Specific Remission: Eye
Tidsramme: Up to 24 months post-infusion months
Improvement of blepheratis evaluated by physical examination.
Up to 24 months post-infusion months
Reduction of Concomitant Therapy
Tidsramme: Up to 24 months
Reduction of corticosteroid therapy or immunosuppressive treatment
Up to 24 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Assistance Publique - Hôpitaux de Paris

Samarbeidspartnere

URC-CIC Paris Descartes Necker Cochin

Etterforskere

  • Studiestol: Emmanuelle SIX, MD, PhD, Institut Imagine

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

1. september 2026

Primær fullføring (Antatt)

1. september 2028

Studiet fullført (Antatt)

1. januar 2029

Datoer for studieregistrering

Først innsendt

20. april 2026

Først innsendt som oppfylte QC-kriteriene

6. juli 2026

Først lagt ut (Faktiske)

13. juli 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

13. juli 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

6. juli 2026

Sist bekreftet

1. juni 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • APHP251137
  • 2025-523305-15-00 (Ctis)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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