A Phase 1 interventional study of CD4^LVFOXP3 in IPEX, sponsored by Bacchetta, Rosa, MD. Recruiting at 1 site in United States. Open to male participants aged 4 Months to 35 Years. Per ClinicalTrials.gov, last updated 2025-05-22.
Sponsored by Bacchetta, Rosa, MD · Phase 1, Interventional, and Treatment
This first-in-human, Phase 1 clinical trial will test the feasibility of the manufacturing and the safety of the administration of CD4\^LVFOXP3 in up to 30 evaluable human participants with IPEX and evaluate the impact of the CD4\^LVFOXP3 infusion on the disease.
Treatment with CD4\^LVFOXP3 is expected to replace the defective Treg cells of the participants, and restore control of the immune system and therefore ameliorate symptoms of IPEX.
We expect to learn the following from this study:
This Phase 1 (feasibility and safety) trial will gather data about CD4\^LVFOXP3 in vivo persistency and early signs of impact on symptoms of IPEX.
This is the only study on the registry with Bacchetta, Rosa, MD as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
The first participant in Dose Level 1 will be administered 1.0 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If there is no toxicity observed in the first participant, the following participants in Dose Level 1 will be administered the same dose of 1.0 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If there is no toxicity observed in any participants in Dose Level 1, participants will be enrolled into Dose Level 2 and administered 3 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If there is no toxicity observed in any participants in Dose Level 2, participants will be enrolled into Dose Level 3 and administered 10 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If in any dose level 1 of 2 participants show toxicity, that dose level will be expanded to 6 participants.
Biological: CD4^LVFOXP3
Participants in Cohort B will always follow treatment of participants in Cohort A for the same dose level. Cohort B will start at Dose Level 2 and be administered 3 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If there is no toxicity observed in any participants in Dose Level 2, participants will be enrolled into Dose Level 3 and administered 10 x 10\^6 CD4\^LVFOXP3 /kg (± 20%). If in any dose level 1 of 2 participants show toxicity, that dose level will be expanded to 6 participants.
Biological: CD4^LVFOXP3
Infusion of autologous CD4+ T cells that have undergone lentiviral-mediated gene transfer of: i) healthy human FOXP3 gene leading to persistent high FOXP3 expression and acquisition of Treg-like cell function; and ii) human CD271 surface marker gene that allows tracking and quantification of the CD4\^LVFOXP3 in the blood.
Also known as: CD4^LVFOXP3 Treg-like cells
Meet target cell number for dose manufacturing
No more than two products fail the target cell dose and established release criteria.
Time frame: Time at release from manufacturing (by Day 0 [infusion day] for each participant)
Find the safe maximum tolerated dose
No more than 1 out of 6 participants may experience a related dose limiting toxicity or treatment emergent adverse events.
Time frame: Up to 60 days post-infusion for each participant
Change in Diarrhea incidence
Stool Diary records - extent of diarrhea as measured by frequency and volume of stools, and the presence or absence of blood and/or mucus, and stool studies at specified time points (for all ages).
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (daily for the first month followed by monthly at Month 2, 3, 6, 9, 12)
Change in GI Symptoms - Gastrointestinal Symptoms Rating Scale
Gastrointestinal Symptoms Rating Scale (GSRS) (for patients ≥12 years old).
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3) through post-infusion (Week 4, Month 6, Month 12)
Change in Body Mass Index (BMI)
BMI measured as kg/m\^2.
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 1, 2, 3, Week 1, 2, 3, 4; Month 2, 3, 6, 9, 12)
Change in age-specific percentiles of height
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3) through post-infusion (Month 12)
Change in age-specific percentiles of bodyweight
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 1, 2, 3, Week 1, 2, 3, 4; Month 2, 3, 6, 9, 12)
Change in Bilirubin levels
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 2, Week 1, 2, 3, 4; Month 2, 3, 6, 9 and 12)
Change in Liver Enzyme - Alanine Transaminase (ALT)
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 2, Week 1, 2, 3, 4; Month 2, 3, 6, 9 and 12)
Change in Liver Enzyme - Aspartate Transaminase (AST)
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 2, Week 1, 2, 3, 4; Month 2, 3, 6, 9 and 12)
Change in Liver Enzyme - Alkaline Phosphatase (ALP)
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 2, Week 1, 2, 3, 4; Month 2, 3, 6, 9 and 12)
Change in Liver Enzyme - Gamma Glutyltranspeptidase (GGT)
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 2, Week 1, 2, 3, 4; Month 2, 3, 6, 9 and 12)
Change in INR level
International normalized ratio (INR) to determine prothrombin time.
Time frame: Baseline/screening (up to 60 days before infusion of CD4^LVFOXP3) through post-infusion (Week 4; Month 3, 6, 12)
Skin Disease (EASI) - Changes from Baseline/ Pre-infusion
Scoring of areas of involvement in each anatomical region (area), calculation of intensity using Eczema Area and Severity Index (EASI).
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), through post-infusion (Day 1; Week 1, 2, 3, 4; Month 3, 6 and 12)
Skin Disease (POEM) - Changes from Baseline/ Pre-infusion
Scoring of areas of involvement in each anatomical region (area), calculation of intensity using Patient oriented eczema measure (POEM).
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), through post-infusion (Day 1; Week 1, 2, 3, 4; Month 3, 6 and 12)
Skin Disease (PASI) - Changes from Baseline/ Pre-infusion
Changes in the extent (%) and severity of skin lesions and their complications (i.e. infections, atrophy, itching) using Psoriasis Area and Severity Index (PASI).
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), through post-infusion (Day 1; Week 1, 2, 3, 4; Month 3, 6 and 12)
Skin Disease (MTLSS) - Changes from Baseline/ Pre-infusion
Changes in the extent (%) and severity of skin lesions and their complications (i.e. infections, atrophy, itching) using Modified Total Lesional Sign Score (MTLSS).
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), through post-infusion (Day 1; Week 1, 2, 3, 4; Month 3, 6 and 12)
Change in skin barrier function
Biophysical Skin Evaluation: Skin measurement of transepidermal water loss to monitor skin barrier function and erythema
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), through post-infusion (Day 1; Week 1, 2, 3, 4; Month 3, 6 and 12)
Change in Hemolytic Anemia (RBC)
Measurement of the number of red blood cells (Complete Blood Counts with Differential \[CBCD\]).
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 1, 2, 3; Week 1, 2, 3, 4; Month 2, 3, 6, 9, 12)
Change in Hemolytic Anemia (Reticulocyte)
Measurement of the number of reticulocytes.
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 1, 2, 3; Week 1, 2, 3, 4; Month 2, 3, 6, 9, 12)
Change in Thrombocytopenia
Measure the number of platelets (Complete Blood Counts with Differential (CBCD)).
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 1, 2, 3; Week 1, 2, 3, 4; Month 2, 3, 6, 9, 12)
Change in Neutropenia
Measure the number of neutrophils (Complete Blood Counts with Differential \[CBCD\]).
Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3), pre-infusion through post-infusion (Day 1, 2, 3; Week 1, 2, 3, 4; Month 2, 3, 6, 9, 12)
Change in C-peptide - Type 1 diabetes Pre-onset
Time frame: Baseline taken 60-30 days before infusion of CD4^LVFOXP3; Post-infusion (Week 4, Month 3, 6 and 12).
Change in HbA1c - Type 1 diabetes Pre-onset
Time frame: Baseline taken 60-30 days before infusion of CD4^LVFOXP3; Post-infusion (Week 4, Month 3, 6 and 12).
Change in Daily insulin requirement - Type 1 diabetes monitoring
Mean daily insulin use recorded over 7 consecutive days preceding each evaluation timepoint for patients with Type 1 Diabetes.
Time frame: Baseline taken 60-30 days before infusion of CD4^LVFOXP3 and post-infusion (over 7 consecutive days preceding each study visit);
Change in hyper-/hypo-glycemic events - Type 1 diabetes monitoring
Continuous glucose monitoring (CGM) metrics to log episodes of hyper/hypoglycemic events.
Time frame: Baseline taken 60-30 days before infusion of CD4^LVFOXP3 and post-infusion (over 7 consecutive days preceding each study visit);
Change in Autoantibody Profile
Measure autoantibodies to organs involved in the disease (participant-specific): anti-insulin (IAA), anti-islet antigens (IA), anti-glutamic acid decarboxylase (GAD), anti-zinc transporter8 (ZNT8), anti-islet cells (ICA), anti-liver kidney microsome (LKM), anti-thyroperoxidase (TPO), anti-thyroglobulin (TG), anti-enterocytes, anti-SMA
Time frame: Screening/ Baseline, Post-infusion (Month 6 and 12)
Change in Creatinine as a measure of Kidney Function
Measure kidney functional parameters, i.e., creatinine, in the blood and urine.
Time frame: Baseline taken 60-30 days before infusion of CD4^LVFOXP3, Pre-infusion, Week 1, 2, 3, 4; Month 2, 3, 6, 9 and 12
Change in PedsQL General Well-Being Scale - Quality of Life
Time frame: Pre-Infusion; Month 6, 12
Change in PedsQL Generic Core Scale - Quality of Life
Time frame: Pre-Infusion; Month 6, 12
Change in PedsQL Gastrointestinal Symptoms Scale - Quality of Life
Measured with Gastrointestinal Symptoms Scale: minimum value = 0 (never a problem), maximum value = 4 (almost always a problem). Higher scores mean a worse outcome.
Time frame: Pre-Infusion; Month 6, 12
Disease-free Survival - Changes from Baseline
The length of time from cell infusion to the point at which the participant survives without any new or worsening of existing signs or symptoms of disease. The data will be compared with historical disease-free survival probability. Probability of disease-free survival will be computed with the use of Kaplan-Meier estimator.
Time frame: Up to 15 years
Overall Survival - Changes from Baseline
Participant survival
Time frame: Up to 15 years
Plan to share: No
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