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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)

2026年7月6日 更新者：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.

調査の概要

状態

まだ募集していません

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (推定)

5

段階

  • フェーズ2
  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

  • 名前：Marina CAVAZZANA, MD, PhD
  • 電話番号：+ 33 01 44 49 50 68
  • メール：m.cavazzana@aphp.fr

研究連絡先のバックアップ

  • 名前：Aline DECHANET, Project Manager
  • 電話番号：+33 01 44 38 17 11
  • メール：aline.dechanet@aphp.fr

研究場所

  • フランス
    • Île-de-France Region
      • Paris、Île-de-France Region、フランス、75015
        • Department of Biotherapy, Hopital Necker Enfants malades
        • コンタクト：

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 子
  • 大人

健康ボランティアの受け入れ

いいえ

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：なし
  • 介入モデル：単一グループの割り当て
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：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.
遺伝的：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)
薬：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)
他の名前：
  • Adeleuskin or IL2

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Frequency of clinical AEs and pathological variations of laboratory parameters
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：Up to 24 months post-infusion
Up to 24 months post-infusion
Persistence of recirculating LNGFR+among CD4+ T cells
時間枠：at 3 months post-infusion
Percentage of LNGFR+ among CD4+ T cells
at 3 months post-infusion

二次結果の測定

結果測定
メジャーの説明
時間枠
Persistence of FOXP3-T4 Cells
時間枠：Up to 24 months post-infusion
Persistence of recirculating LNGFR among CD4+ T cells
Up to 24 months post-infusion
Phenotyping
時間枠：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
時間枠：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
時間枠：Beyond 3 months to 24 months post-infusion
Beyond 3 months to 24 months post-infusion
TCR repertoire
時間枠：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
時間枠：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
時間枠：Up to 24 months post-infusion
Diminution of the skin lesions severity
Up to 24 months post-infusion
Organ-Specific Remission: Skin disease
時間枠：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
時間枠：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
時間枠：Up to 24 months post-infusion
Reduction of insulin dose administrered
Up to 24 months post-infusion
Organ-Specific Remission: Endocrine System Function
時間枠：Up to 24 months post-infusion
Reduction of HBA1C
Up to 24 months post-infusion
Organ-Specific Remission: Renal function
時間枠：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
時間枠：Up to 24 months post-infusion months
Improvement of proteinuria
Up to 24 months post-infusion months
Organ-Specific Remission: Renal function
時間枠：Up to 24 months post-infusion months
Improvement of tubular effect
Up to 24 months post-infusion months
Organ-Specific Remission: Digestive System
時間枠：Up to 24 months post-infusion months
Change in the weight curve
Up to 24 months post-infusion months
Organ-Specific Remission: Digestive System
時間枠：Up to 24 months post-infusion months
Change in diarrhea incidence
Up to 24 months post-infusion months
Organ-Specific Remission: Digestive System
時間枠：Up to 24 months post-infusion months
Decrease of fecal calprotectin
Up to 24 months post-infusion months
Organ-Specific Remission: Musculoskeletal System
時間枠：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
時間枠：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
時間枠：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
時間枠：Up to 24 months post-infusion months
Presence of autoimmune hemolytic anemia
Up to 24 months post-infusion months
Organ-Specific Remission: Blood count
時間枠：Up to 24 months post-infusion months
Presence of thrombocytopenia
Up to 24 months post-infusion months
Organ-Specific Remission: Eye
時間枠：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
時間枠：Up to 24 months
Reduction of corticosteroid therapy or immunosuppressive treatment
Up to 24 months

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Assistance Publique - Hôpitaux de Paris

協力者

URC-CIC Paris Descartes Necker Cochin

捜査官

  • スタディチェア：Emmanuelle SIX, MD, PhD、Institut Imagine

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年9月1日

一次修了 (推定)

2028年9月1日

研究の完了 (推定)

2029年1月1日

試験登録日

最初に提出

2026年4月20日

QC基準を満たした最初の提出物

2026年7月6日

最初の投稿 (実際)

2026年7月13日

学習記録の更新

投稿された最後の更新 (実際)

2026年7月13日

QC基準を満たした最後の更新が送信されました

2026年7月6日

最終確認日

2026年6月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

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

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いいえ

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