IPEXPhase 1NCT05241444

CD4^LVFOXP3 in Participants With IPEX

A Phase 1 study testing CD4^LVFOXP3 in people with IPEX, run by Bacchetta, Rosa, MD at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Trial summary

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. Read more about this study

Who is it for?: Ages 4 months to 35 years, men only
Conditions the study is for: IPEX
What is being tested?: CD4^LVFOXP3
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 1 siteUnited States
Study dates: 22 Mar 2022to Oct 2027
Phase: Phase 1
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 4 months to 35 years
Men only
No healthy volunteers
Child, Adult

Who may be able to join

Body weight greater than 8 kg, unless assessed as able to tolerate leukapheresis
FOXP3 gene mutation
Medical history of progressive symptoms of IPEX with persistency of some symptoms and/or signs requiring immune suppressive medication. The participant may or may not be on immunosuppression at time of starting the study.
Uncontrolled IPEX disease but unable to tolerate immune suppressive medication
Recurrent IPEX symptoms, requiring immune suppressive medications, in participants who have had prior allogeneic (allo) blood stem cell transplantation (HSCT).
≥ 50% Performance rating on Lansky/Karnofsky Scale

Show all 9Show fewer

Organ and marrow function within acceptable levels of function
Absence of ongoing infections
Must be able to consent if an adult

Who cannot join

Medical instability
Less than 6 months life expectancy
Inability to meet limits for steroid dosing
Eligible for an HLA matched sibling or matched unrelated donor blood stem cell transplant, and be willing to undergo transplant.
Unrelated or comorbid disease
Allergy to any study medication, product, or intervention
Currently receiving another experimental treatment
History of malignancy, unless disease free for at least 2 years, with the exception of non melanoma skin cancer or carcinoma in situ

Trial locations and contacts

1 site in 1 country.

United States1 site

Lucile Packard Children's Hospital
Palo Alto, California, 94305

Other trials in United States

About this study

Official title: Phase 1 Study of Autologous CD4^LVFOXP3 in Participants With Immune Dysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) Syndrome

Read the detailed description

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:

That CD4^LVFOXP3 can be consistently produced and be of expected quality to be used in humans,
That CD4^LVFOXP3 are safe in children and young adults with IPEX, and determine its effects, both good and bad,
That CD4^LVFOXP3 can improve overall health and allow reduction of medication/s.

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.

Conditions: IPEX
Being tested: CD4^LVFOXP3
Keywords: Treg cells, Regulatory T cells, Gene therapy, autoimmunity, Immune Dysregulation Polyendocrinopathy Enteropathy X-linked, FOXP3, Lentiviral, CD271, NGFR, immune suppression
Medical subject headings: Autoimmune Diseases

What participants receive

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

CD4^LVFOXP3Biological
Also called CD4^LVFOXP3 Treg-like cells
Infusion of autologous CD4+ T cells that have undergone lentiviral-mediated gene transfer of:
1. 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.

Study groups in NCT05241444
Study group	Role	What they receive
Cohort A (≥12 years)	Experimental	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. If there is no toxicity observed in any participants in Dose Level 3, participants will then be administered 10 x 10^6 CD4^LVFOXP3 /kg (± 20%) at two time points 21-42 days apart. Receives: Biological: CD4^LVFOXP3
Cohort B (<12 years)	Experimental	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. If there is no toxicity observed in any participants in Dose Level 3, participants will then be administered 10 x 10^6 CD4^LVFOXP3 /kg (± 20%) at two time points 21-42 days apart. Receives: Biological: CD4^LVFOXP3

What is being measured

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

Meet target cell number for dose manufacturing
No more than two products fail the target cell dose and established release criteria.
Measured: 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.
Measured: Up to 60 days post-infusion for each participant

Secondary outcomes (31)

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).
Measured: 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).
Measured: 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.
Measured: 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
Measured: Baseline (up to 60 days before infusion of CD4^LVFOXP3) through post-infusion (Month 12)
Change in age-specific percentiles of bodyweight
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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
Measured: 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]).
Measured: 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.
Measured: 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)).
Measured: 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]).
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: Pre-Infusion; Month 6, 12
Change in PedsQL Generic Core Scale - Quality of Life
Measured: 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.
Measured: 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.
Measured: Up to 15 years
Overall Survival - Changes from Baseline
Participant survival
Measured: Up to 15 years

Timeline

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

22 Mar 2022Oct 2027

First posted15 Feb 2022
Study start22 Mar 2022
Primary completionDec 2026 (estimated)
Study completionOct 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (25)Papers the sponsor has linked to this study.
Other trials for IPEXStudies of the same condition, open and under way.
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
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: Escalating doses of CD4\^LVFOXP3 will be administered in 2-6 participants per dose in two age cohorts (Cohort A: ≥ 12 years of age; Cohort B: \< 12 years of age) using a 2+4 dose escalation design. Cohort B will be started at the second dose level.
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05241444
Sponsor's protocol ID: IRB-63373
Other IDs: CLIN2-13259, 1R01FD007540, DRU-2020-7764, RPD-2020-470
Status last verified: Nov 2026
First submitted: 12 Jan 2022
Last updated: 5 Nov 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Sato Y, Nathan A, Shipp S, Wright JF, Tate KM, Wani P, Roncarolo MG, Bacchetta R. A novel FOXP3 knockout-humanized mouse model for pre-clinical safety and efficacy evaluation of Treg-like cell products. Mol Ther Methods Clin Dev. 2023 Nov 7;31:101150. doi: 10.1016/j.omtm.2023.101150. eCollection 2023 Dec 14.
PubMed 38027059
Allan SE, Alstad AN, Merindol N, Crellin NK, Amendola M, Bacchetta R, Naldini L, Roncarolo MG, Soudeyns H, Levings MK. Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. Mol Ther. 2008 Jan;16(1):194-202. doi: 10.1038/sj.mt.6300341. Epub 2007 Nov 6.
PubMed 17984976
Amendola M, Venneri MA, Biffi A, Vigna E, Naldini L. Coordinate dual-gene transgenesis by lentiviral vectors carrying synthetic bidirectional promoters. Nat Biotechnol. 2005 Jan;23(1):108-16. doi: 10.1038/nbt1049. Epub 2004 Dec 26.
PubMed 15619618
Baecher-Allan CM, Hafler DA. The purification and functional analysis of human CD4+CD25high regulatory T cells. Curr Protoc Immunol. 2006 May;Chapter 7:7.4B.1-7.4B.12. doi: 10.1002/0471142735.im0704bs72.
PubMed 18432975
Barzaghi F, Passerini L, Gambineri E, Ciullini Mannurita S, Cornu T, Kang ES, Choe YH, Cancrini C, Corrente S, Ciccocioppo R, Cecconi M, Zuin G, Discepolo V, Sartirana C, Schmidtko J, Ikinciogullari A, Ambrosi A, Roncarolo MG, Olek S, Bacchetta R. Demethylation analysis of the FOXP3 locus shows quantitative defects of regulatory T cells in IPEX-like syndrome. J Autoimmun. 2012 Feb;38(1):49-58. doi: 10.1016/j.jaut.2011.12.009. Epub 2012 Jan 20.
PubMed 22264504
Barzaghi F, Amaya Hernandez LC, Neven B, Ricci S, Kucuk ZY, Bleesing JJ, Nademi Z, Slatter MA, Ulloa ER, Shcherbina A, Roppelt A, Worth A, Silva J, Aiuti A, Murguia-Favela L, Speckmann C, Carneiro-Sampaio M, Fernandes JF, Baris S, Ozen A, Karakoc-Aydiner E, Kiykim A, Schulz A, Steinmann S, Notarangelo LD, Gambineri E, Lionetti P, Shearer WT, Forbes LR, Martinez C, Moshous D, Blanche S, Fisher A, Ruemmele FM, Tissandier C, Ouachee-Chardin M, Rieux-Laucat F, Cavazzana M, Qasim W, Lucarelli B, Albert MH, Kobayashi I, Alonso L, Diaz De Heredia C, Kanegane H, Lawitschka A, Seo JJ, Gonzalez-Vicent M, Diaz MA, Goyal RK, Sauer MG, Yesilipek A, Kim M, Yilmaz-Demirdag Y, Bhatia M, Khlevner J, Richmond Padilla EJ, Martino S, Montin D, Neth O, Molinos-Quintana A, Valverde-Fernandez J, Broides A, Pinsk V, Ballauf A, Haerynck F, Bordon V, Dhooge C, Garcia-Lloret ML, Bredius RG, Kalwak K, Haddad E, Seidel MG, Duckers G, Pai SY, Dvorak CC, Ehl S, Locatelli F, Goldman F, Gennery AR, Cowan MJ, Roncarolo MG, Bacchetta R; Primary Immune Deficiency Treatment Consortium (PIDTC) and the Inborn Errors Working Party (IEWP) of the European Society for Blood and Marrow Transplantation (EBMT). Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study. J Allergy Clin Immunol. 2018 Mar;141(3):1036-1049.e5. doi: 10.1016/j.jaci.2017.10.041. Epub 2017 Dec 11.
PubMed 29241729
Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood. 2005 Jun 15;105(12):4743-8. doi: 10.1182/blood-2004-10-3932. Epub 2005 Mar 3.
PubMed 15746082
Bluestone JA, Tang Q. Treg cells-the next frontier of cell therapy. Science. 2018 Oct 12;362(6411):154-155. doi: 10.1126/science.aau2688. No abstract available.
PubMed 30309932
Bluestone JA, Buckner JH, Fitch M, Gitelman SE, Gupta S, Hellerstein MK, Herold KC, Lares A, Lee MR, Li K, Liu W, Long SA, Masiello LM, Nguyen V, Putnam AL, Rieck M, Sayre PH, Tang Q. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015 Nov 25;7(315):315ra189. doi: 10.1126/scitranslmed.aad4134.
PubMed 26606968
Bonini C, Grez M, Traversari C, Ciceri F, Marktel S, Ferrari G, Dinauer M, Sadat M, Aiuti A, Deola S, Radrizzani M, Hagenbeek A, Apperley J, Ebeling S, Martens A, Kolb HJ, Weber M, Lotti F, Grande A, Weissinger E, Bueren JA, Lamana M, Falkenburg JH, Heemskerk MH, Austin T, Kornblau S, Marini F, Benati C, Magnani Z, Cazzaniga S, Toma S, Gallo-Stampino C, Introna M, Slavin S, Greenberg PD, Bregni M, Mavilio F, Bordignon C. Safety of retroviral gene marking with a truncated NGF receptor. Nat Med. 2003 Apr;9(4):367-9. doi: 10.1038/nm0403-367. No abstract available.
PubMed 12669036
Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB, Yasayko SA, Wilkinson JE, Galas D, Ziegler SF, Ramsdell F. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet. 2001 Jan;27(1):68-73. doi: 10.1038/83784.
PubMed 11138001
Consonni F, Ciullini Mannurita S, Gambineri E. Atypical Presentations of IPEX: Expect the Unexpected. Front Pediatr. 2021 Feb 5;9:643094. doi: 10.3389/fped.2021.643094. eCollection 2021.
PubMed 33614561
Brunstein CG, Miller JS, McKenna DH, Hippen KL, DeFor TE, Sumstad D, Curtsinger J, Verneris MR, MacMillan ML, Levine BL, Riley JL, June CH, Le C, Weisdorf DJ, McGlave PB, Blazar BR, Wagner JE. Umbilical cord blood-derived T regulatory cells to prevent GVHD: kinetics, toxicity profile, and clinical effect. Blood. 2016 Feb 25;127(8):1044-51. doi: 10.1182/blood-2015-06-653667. Epub 2015 Nov 12.
PubMed 26563133
Cornetta K, Duffy L, Turtle CJ, Jensen M, Forman S, Binder-Scholl G, Fry T, Chew A, Maloney DG, June CH. Absence of Replication-Competent Lentivirus in the Clinic: Analysis of Infused T Cell Products. Mol Ther. 2018 Jan 3;26(1):280-288. doi: 10.1016/j.ymthe.2017.09.008. Epub 2017 Sep 12.
PubMed 28970045
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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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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.
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Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
Common Variable Immunodeficiency (CVID), Primary Immune Regulatory Disorder
Not yet recruitingObservational study
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Intraductal Papillary Mucinous Neoplasms, Pancreatic Exocrine Insufficiency
RecruitingEarly Phase 1
Expanded Access Protocol Using CD3+/CD19+ Depleted PBSC
Leukemia, Inborn Errors of Metabolism
RecruitingObservational study
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All IPEX trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1 Study of Autologous CD4^LVFOXP3 in Participants With Immune Dysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) Syndrome
ClinicalTrials.gov ID: NCT05241444
Acronym / sponsor ID: IRB-63373
Conditions: IPEX
Keywords: Treg cells, Regulatory T cells, Gene therapy, autoimmunity, Immune Dysregulation Polyendocrinopathy Enteropathy X-linked, FOXP3, Lentiviral, CD271
Phase: Phase 1
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 16 participants (actual)
Lead sponsor: Bacchetta, Rosa, MDUniversity, hospital or other
Collaborators: California Institute for Regenerative Medicine (CIRM), Food and Drug Administration (FDA)
Study start: 22 Mar 2022 (actual)
Primary completion: Dec 2026 (estimated)
Study completion: Oct 2027 (estimated)
First posted: 15 Feb 2022 (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.

Detailed description

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:

That CD4^LVFOXP3 can be consistently produced and be of expected quality to be used in humans,
That CD4^LVFOXP3 are safe in children and young adults with IPEX, and determine its effects, both good and bad,
That CD4^LVFOXP3 can improve overall health and allow reduction of medication/s.

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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2
Model description: Escalating doses of CD4^LVFOXP3 will be administered in 2-6 participants per dose in two age cohorts (Cohort A: ≥ 12 years of age; Cohort B: < 12 years of age) using a 2+4 dose escalation design. Cohort B will be started at the second dose level.

Arm	Type	Receives
Cohort A (≥12 years)	Experimental	Biological: CD4^LVFOXP3The 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. If there is no toxicity observed in any participants in Dose Level 3, participants will then be administered 10 x 10^6 CD4^LVFOXP3 /kg (± 20%) at two time points 21-42 days apart.
Cohort B (<12 years)	Experimental	Biological: CD4^LVFOXP3Participants 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. If there is no toxicity observed in any participants in Dose Level 3, participants will then be administered 10 x 10^6 CD4^LVFOXP3 /kg (± 20%) at two time points 21-42 days apart.

Who may qualify

Ages: 4 months to 35 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (9 listed)

Body weight greater than 8 kg, unless assessed as able to tolerate leukapheresis
FOXP3 gene mutation
Medical history of progressive symptoms of IPEX with persistency of some symptoms and/or signs requiring immune suppressive medication. The participant may or may not be on immunosuppression at time of starting the study.
Uncontrolled IPEX disease but unable to tolerate immune suppressive medication
Recurrent IPEX symptoms, requiring immune suppressive medications, in participants who have had prior allogeneic (allo) blood stem cell transplantation (HSCT).

Key exclusion criteria (8 listed)

Medical instability
Less than 6 months life expectancy
Inability to meet limits for steroid dosing
Eligible for an HLA matched sibling or matched unrelated donor blood stem cell transplant, and be willing to undergo transplant.
Unrelated or comorbid disease

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
CD4^LVFOXP3Also: CD4^LVFOXP3 Treg-like cellsInfusion 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.	Biological	Cohort A (≥12 years), Cohort B (<12 years)

Primary outcome

Meet target cell number for dose manufacturing
Time frame: Time at release from manufacturing (by Day 0 [infusion day] for each participant)
No more than two products fail the target cell dose and established release criteria.
Find the safe maximum tolerated dose
Time frame: Up to 60 days post-infusion for each participant
No more than 1 out of 6 participants may experience a related dose limiting toxicity or treatment emergent adverse events.

31 secondary outcomes

Change in Diarrhea incidence
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
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)
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
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
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
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
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
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
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)
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)
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
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
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
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
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
Time frame: Screening/ Baseline, Post-infusion (Month 6 and 12)
Change in Creatinine as a measure of Kidney Function
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
Time frame: Pre-Infusion; Month 6, 12
Disease-free Survival - Changes from Baseline
Time frame: Up to 15 years
Overall Survival - Changes from Baseline
Time frame: Up to 15 years

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 5 Nov 2026.
Background: PubMed 38027059Sato Y, Nathan A, Shipp S, Wright JF, Tate KM, Wani P, Roncarolo MG, Bacchetta R. A novel FOXP3 knockout-humanized mouse model for pre-clinical safety and efficacy evaluation of Treg-like cell products. Mol Ther Methods Clin Dev. 2023 Nov 7;31:101150. doi: 10.1016/j.omtm.2023.101150. eCollection 2023 Dec 14.
Background: PubMed 17984976Allan SE, Alstad AN, Merindol N, Crellin NK, Amendola M, Bacchetta R, Naldini L, Roncarolo MG, Soudeyns H, Levings MK. Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. Mol Ther. 2008 Jan;16(1):194-202. doi: 10.1038/sj.mt.6300341. Epub 2007 Nov 6.
Background: PubMed 15619618Amendola M, Venneri MA, Biffi A, Vigna E, Naldini L. Coordinate dual-gene transgenesis by lentiviral vectors carrying synthetic bidirectional promoters. Nat Biotechnol. 2005 Jan;23(1):108-16. doi: 10.1038/nbt1049. Epub 2004 Dec 26.
Background: PubMed 18432975Baecher-Allan CM, Hafler DA. The purification and functional analysis of human CD4+CD25high regulatory T cells. Curr Protoc Immunol. 2006 May;Chapter 7:7.4B.1-7.4B.12. doi: 10.1002/0471142735.im0704bs72.
Background: PubMed 22264504Barzaghi F, Passerini L, Gambineri E, Ciullini Mannurita S, Cornu T, Kang ES, Choe YH, Cancrini C, Corrente S, Ciccocioppo R, Cecconi M, Zuin G, Discepolo V, Sartirana C, Schmidtko J, Ikinciogullari A, Ambrosi A, Roncarolo MG, Olek S, Bacchetta R. Demethylation analysis of the FOXP3 locus shows quantitative defects of regulatory T cells in IPEX-like syndrome. J Autoimmun. 2012 Feb;38(1):49-58. doi: 10.1016/j.jaut.2011.12.009. Epub 2012 Jan 20.
Background: PubMed 29241729Barzaghi F, Amaya Hernandez LC, Neven B, Ricci S, Kucuk ZY, Bleesing JJ, Nademi Z, Slatter MA, Ulloa ER, Shcherbina A, Roppelt A, Worth A, Silva J, Aiuti A, Murguia-Favela L, Speckmann C, Carneiro-Sampaio M, Fernandes JF, Baris S, Ozen A, Karakoc-Aydiner E, Kiykim A, Schulz A, Steinmann S, Notarangelo LD, Gambineri E, Lionetti P, Shearer WT, Forbes LR, Martinez C, Moshous D, Blanche S, Fisher A, Ruemmele FM, Tissandier C, Ouachee-Chardin M, Rieux-Laucat F, Cavazzana M, Qasim W, Lucarelli B, Albert MH, Kobayashi I, Alonso L, Diaz De Heredia C, Kanegane H, Lawitschka A, Seo JJ, Gonzalez-Vicent M, Diaz MA, Goyal RK, Sauer MG, Yesilipek A, Kim M, Yilmaz-Demirdag Y, Bhatia M, Khlevner J, Richmond Padilla EJ, Martino S, Montin D, Neth O, Molinos-Quintana A, Valverde-Fernandez J, Broides A, Pinsk V, Ballauf A, Haerynck F, Bordon V, Dhooge C, Garcia-Lloret ML, Bredius RG, Kalwak K, Haddad E, Seidel MG, Duckers G, Pai SY, Dvorak CC, Ehl S, Locatelli F, Goldman F, Gennery AR, Cowan MJ, Roncarolo MG, Bacchetta R; Primary Immune Deficiency Treatment Consortium (PIDTC) and the Inborn Errors Working Party (IEWP) of the European Society for Blood and Marrow Transplantation (EBMT). Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study. J Allergy Clin Immunol. 2018 Mar;141(3):1036-1049.e5. doi: 10.1016/j.jaci.2017.10.041. Epub 2017 Dec 11.
Background: PubMed 15746082Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood. 2005 Jun 15;105(12):4743-8. doi: 10.1182/blood-2004-10-3932. Epub 2005 Mar 3.
Background: PubMed 30309932Bluestone JA, Tang Q. Treg cells-the next frontier of cell therapy. Science. 2018 Oct 12;362(6411):154-155. doi: 10.1126/science.aau2688. No abstract available.
Background: PubMed 26606968Bluestone JA, Buckner JH, Fitch M, Gitelman SE, Gupta S, Hellerstein MK, Herold KC, Lares A, Lee MR, Li K, Liu W, Long SA, Masiello LM, Nguyen V, Putnam AL, Rieck M, Sayre PH, Tang Q. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015 Nov 25;7(315):315ra189. doi: 10.1126/scitranslmed.aad4134.
Background: PubMed 12669036Bonini C, Grez M, Traversari C, Ciceri F, Marktel S, Ferrari G, Dinauer M, Sadat M, Aiuti A, Deola S, Radrizzani M, Hagenbeek A, Apperley J, Ebeling S, Martens A, Kolb HJ, Weber M, Lotti F, Grande A, Weissinger E, Bueren JA, Lamana M, Falkenburg JH, Heemskerk MH, Austin T, Kornblau S, Marini F, Benati C, Magnani Z, Cazzaniga S, Toma S, Gallo-Stampino C, Introna M, Slavin S, Greenberg PD, Bregni M, Mavilio F, Bordignon C. Safety of retroviral gene marking with a truncated NGF receptor. Nat Med. 2003 Apr;9(4):367-9. doi: 10.1038/nm0403-367. No abstract available.
Background: PubMed 11138001Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB, Yasayko SA, Wilkinson JE, Galas D, Ziegler SF, Ramsdell F. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet. 2001 Jan;27(1):68-73. doi: 10.1038/83784.
Background: PubMed 33614561Consonni F, Ciullini Mannurita S, Gambineri E. Atypical Presentations of IPEX: Expect the Unexpected. Front Pediatr. 2021 Feb 5;9:643094. doi: 10.3389/fped.2021.643094. eCollection 2021.
Individual participant dataSharing planned: No

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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. This study is not recruiting at the moment.

Jessie Alexander, MD principal investigator

Stanford University

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CD4^LVFOXP3 in people with IPEX, run by Bacchetta, Rosa, MD at 1 site in United States.

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 9 inclusion and 8 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: under way, not looking for participants, as of the sponsor's last update on 5 Nov 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 United States. 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 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.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Meet target cell number for dose manufacturing (time frame: Time at release from manufacturing (by Day 0 [infusion day] for each participant)). The study lists 2 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 NCT05241444, which also lists 25 linked publications.

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 5 Nov 2026.