Phase I/II Open‑Label Study Assessing Safety and Efficacy of LV‑FOXP3‑T4 Induced CD4⁺ Treg Cell Therapy ± Low‑Dose Aldesleukin in Patients with IPEX Syndrome

The primary objective is to evaluate the initial safety and efficacy of treatment with FOXP3-T4 alone or combined with low‑dose interleukin‑2, including the procedural steps and infusion of LV‑FOXP3‑LNGFR lentiviral vector‑modified induced CD4⁺ regulatory T cells in patients with IPEX syndrome.

The secondary objective is to assess the efficacy of the same treatment regimens.

The trial enrolled male patients aged 1–45 years with molecularly confirmed IPEX syndrome caused by FOXP3 mutations; the sponsor did not provide the total number of participants. Selection required a confirmed genetic diagnosis, presence of active or controlled autoimmune complications, and prior use of immunosuppressive therapy, with eligibility beginning at the second line of treatment when hematopoietic stem cell transplantation was not feasible or a suitable donor was unavailable. Additional criteria included prior allogeneic HSCT with engraftment failure, recurrent disease symptoms, informed consent from a parent or guardian, use of effective contraception for patients of child‑bearing potential, and affiliation with a French or European social security scheme. General health status was limited to patients under immunosuppressive medication; no specific lifestyle requirements such as diet or physical activity were stipulated.

The THERIPEX trial is a phase I/II open‑label, non‑randomized, monocentric, single‑arm study evaluating the safety and efficacy of FOXP3‑T4 administered as an intravenous infusion of LV‑FOXP3‑LNGFR lentiviral vector‑modified induced CD4⁺ Treg cells, with optional low‑dose IL‑2 subcutaneous supplementation, in male patients aged 1–45 years diagnosed with IPEX syndrome. After a screening visit to confirm eligibility, participants receive the investigational infusion (day 0) followed by a predefined schedule of follow‑up visits at weeks 1, 2, 4, then monthly to month 12, and quarterly thereafter through month 24, culminating in an end‑of‑study visit. The primary objective focuses on safety and efficacy up to 24 months post‑infusion, defined as the primary endpoint, while secondary efficacy assessments are performed over the same period. Participant involvement therefore extends from the initial screening through the 24‑month follow‑up. Early termination may occur if predefined safety stopping rules are met, if a serious adverse event related to the investigational product arises, or if the investigator deems continued participation medically inappropriate. Enrollment is planned to begin May 2026 with an anticipated completion date of May 2031.

The investigational product FOXP3‑T4 is supplied as a dispersion for infusion intended for intravenous administration. It is delivered as an LV‑FOXP3‑LNGFR lentiviral vector‑modified induced CD4⁺ regulatory T‑cell product. The infusion is performed according to a protocol‑specified schedule, with each infusion administered over a defined period under continuous monitoring for infusion‑related reactions and laboratory parameters.

The second investigational agent, ILT‑101 liquide, contains the active substance aldesleukin (recombinant interleukin‑2). It is provided as a solution for injection and administered by subcutaneous injection. Low‑dose regimens are applied in accordance with the study protocol, typically on a daily or alternate‑day basis, with dose adjustments based on tolerability and pharmacodynamic markers.

Both agents may be used sequentially or concurrently as outlined in the trial design. Dosing intervals, infusion rates, and injection sites are recorded in the case report form. Participant compliance is assessed through medication diaries, electronic dosing logs, and regular site visits, with any deviations documented and reported per regulatory requirements.

The trial evaluates efficacy of the FOXP3‑T4 infusion, with or without low‑dose IL‑2, by monitoring outcomes for a period of up to 24 months after the intravenous administration of the investigational product.