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.
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
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.
Single group
FOXP3-T4 drug product
GeneticEach 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-101
DrugThe 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)
Frequency of clinical AEs and pathological variations of laboratory parameters
Number of clinical AEs
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).
Incidence of clinically detectable lymphoproliferation and abnormal clonal dominance
This is measured via Vector Insertion Site Analysis (VISA)
Incidence of clinically detectable lymphoproliferation and abnormal clonal dominance
This is measured by proliferation of LNGFR+ cells
Persistence of FOXP3-T4 Cells
Persistence of recirculating LNGFR among CD4+ T cells
Phenotyping
Deeper phenotyping of FOXP3-T4 (CD4+LNGFR+ CD25+ FOXP3+ CD127low)
Vector Copy Number (VCN) Analysis
Quantification of the transgene copy number (VCN) on drug product and on sorted T-CD4+
Immunophenotyping T and B cells if no change is detected from the baseline (e.g. before treatment), the immunological phenotype
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Assistance Publique - Hôpitaux de Paris
Lead sponsor
URC-CIC Paris Descartes Necker Cochin
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
