The Immune Dysregulation Polyendocrinopathy Enteropathy X-linked Syndrome is a Primary Immunodeficiency Caused by Pathogenic Variants in Forkhead Box Protein 3Phase 1/2THERIPEXNCT07697118

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

A Phase 1/2 study testing FOXP3-T4 drug product and ILT-101 in people with The Immune Dysregulation Polyendocrinopathy Enteropathy X-linked Syndrome is a Primary Immunodeficiency Caused by Pathogenic Variants in Forkhead Box Protein 3, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 1 year to 45 years, men only
Conditions the study is for: The Immune Dysregulation Polyendocrinopathy Enteropathy X-linked Syndrome is a Primary Immunodeficiency Caused by Pathogenic Variants in Forkhead Box Protein 3
What is being tested?: FOXP3-T4 drug product and ILT-101
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteFrance
Study dates: Sep 2026to Jan 2029
Phase: Phase 1/2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 year to 45 years
Men only
No healthy volunteers
Child, Adult

Who may be able to join

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

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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

Who cannot join

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.

Show all 9Show fewer

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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Marina CAVAZZANA, MD, PhD contact

01 44 49 50 68 ext. + 33

m.cavazzana@aphp.fr

Aline DECHANET, Project Manager contact

01 44 38 17 11 ext. +33

aline.dechanet@aphp.fr

France1 site

Department of Biotherapy, Hopital Necker Enfants malades
Paris, Île-de-France Region, 75015
Marina CAVAZZANA, MD, PHD, 01 44 49 50 68 ext. +33, m.cavazzana@aphp.fr

Other trials in France

About this study

Official title: 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.

Read the detailed description

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.

Conditions: The Immune Dysregulation Polyendocrinopathy Enteropathy X-linked Syndrome is a Primary Immunodeficiency Caused by Pathogenic Variants in Forkhead Box Protein 3
Being tested: FOXP3-T4 drug product, ILT-101
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
Medical subject headings: Autoimmune Diseases, Genetic Diseases, Inborn

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FOXP3-T4 drug productGenetic
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)
ILT-101Drug
Also called Adeleuskin or IL2
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)

Study groups in NCT07697118
Study group	Role	What they receive
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. Receives: Genetic: FOXP3-T4 drug product; Drug: ILT-101

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (24)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2026Jan 2029

First posted13 Jul 2026
Study startSep 2026 (estimated)
Primary completionSep 2028 (estimated)
Study completionJan 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for The Immune Dysregulation Polyendocrinopathy Enteropathy X-linked Syndrome is a Primary Immunodeficiency Caused by Pathogenic Variants in Forkhead Box Protein 3Studies of the same condition, open and under way.
More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 5 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07697118
Sponsor's protocol ID: APHP251137
Other IDs: 2025-523305-15-00, 2025
Acronym: THERIPEX
Status last verified: Jun 2026
First submitted: 20 Apr 2026
Last updated: 13 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 33545713

Study at a glance

From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT07697118
Acronym / sponsor ID: THERIPEX / APHP251137
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
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 5 participants (estimated)
Lead sponsor: Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
Collaborators: URC-CIC Paris Descartes Necker Cochin
Study start: Sep 2026 (estimated)
Primary completion: Sep 2028 (estimated)
Study completion: Jan 2029 (estimated)
First posted: 13 Jul 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The study aims to stabilize autoimmune manifestations and potentially cure the underlying disease, ultimately allowing for the discontinuation of ongoing immunosuppressive treatments.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
FOXP3-T4 drug product	Experimental	Genetic: FOXP3-T4 drug product, Drug: ILT-101FOXP3-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.

Who may qualify

Ages: 1 year to 45 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (10 listed)

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

Key exclusion criteria (9 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FOXP3-T4 drug productEach 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)	Genetic	FOXP3-T4 drug product
ILT-101Also: Adeleuskin or IL2The 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)	Drug	FOXP3-T4 drug product

Primary outcome

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

24 secondary outcomes

Persistence of FOXP3-T4 Cells
Time frame: Up to 24 months post-infusion
Phenotyping
Time frame: Up to 24 months post-infusion
Vector Copy Number (VCN) Analysis
Time frame: 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
Time frame: Beyond 3 months to 24 months post-infusion
TCR repertoire
Time frame: At 3 months, 12 months and 24 months, post-infusion
Autoantibodies dosage
Time frame: At 3 months, 6 months, 12 months and 24 months post-infusion
Organ-Specific Remission: Skin disease
Time frame: Up to 24 months post-infusion
Organ-Specific Remission: Skin disease
Time frame: Up to 24 months post-infusion
Organ-Specific Remission: Endocrine System Function
Time frame: Up to 24 months post-infusion
Organ-Specific Remission: Endocrine System Function
Time frame: Up to 24 months post-infusion
Organ-Specific Remission: Endocrine System Function
Time frame: Up to 24 months post-infusion
Organ-Specific Remission: Renal function
Time frame: Up to 24 months post-infusion months
Organ-Specific Remission: Renal function
Time frame: Up to 24 months post-infusion months
Organ-Specific Remission: Renal function
Time frame: Up to 24 months post-infusion months
Organ-Specific Remission: Digestive System
Time frame: Up to 24 months post-infusion months
Organ-Specific Remission: Digestive System
Time frame: Up to 24 months post-infusion months
Organ-Specific Remission: Digestive System
Time frame: Up to 24 months post-infusion months
Organ-Specific Remission: Musculoskeletal System
Time frame: Up to 24 months post-infusion months
Organ-Specific Remission: Respiratory Function
Time frame: Up to 24 months post-infusion months
Organ-Specific Remission: General status
Time frame: Up to 24 months post-infusion months
Organ-Specific Remission: Blood count
Time frame: Up to 24 months post-infusion months
Organ-Specific Remission: Blood count
Time frame: Up to 24 months post-infusion months
Organ-Specific Remission: Eye
Time frame: Up to 24 months post-infusion months
Reduction of Concomitant Therapy
Time frame: Up to 24 months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2026.
Background: PubMed 33545713Delville 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.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Marina CAVAZZANA, MD, PhD contact

01 44 49 50 68 ext. + 33

m.cavazzana@aphp.fr

Aline DECHANET, Project Manager contact

01 44 38 17 11 ext. +33

aline.dechanet@aphp.fr

Emmanuelle SIX, MD, PhD study chair

Institut Imagine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Marina CAVAZZANA, MD, PhD (01 44 49 50 68 ext. + 33, m.cavazzana@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of clinical AEs and pathological variations of laboratory parameters (time frame: Up to 24 months post-infusion). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07697118, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026.