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NCT Number: NCT05241444

CD4^LVFOXP3 in Participants With IPEX

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.

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Key information

Conditions

IPEX Autoimmune Diseases Immune System Diseases

Age range

4 month–35 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Lucile Packard Children's Hospital

Palo Alto, California, 94305, United States

Location status: Recruiting

Location contact

Jessie Alexander

PRINCIPAL_INVESTIGATOR

Rajni Agarwal, MD

SUB_INVESTIGATOR

SCGT Clinical Trials Program

CONTACT

[email protected]

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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

Treatment and study plan

CD4^LVFOXP3

Biological

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.

Other names: CD4^LVFOXP3 Treg-like cells

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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)

    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).

  2. 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)

    Gastrointestinal Symptoms Rating Scale (GSRS) (for patients ≥12 years old).

  3. 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)

    BMI measured as kg/m^2.

  4. Change in age-specific percentiles of height

    Time frame: Baseline (up to 60 days before infusion of CD4^LVFOXP3) through post-infusion (Month 12)

  5. 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)

  6. 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)

  7. 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)

  8. 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)

  9. 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)

  10. 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)

  11. 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)

    International normalized ratio (INR) to determine prothrombin time.

  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)

    Scoring of areas of involvement in each anatomical region (area), calculation of intensity using Eczema Area and Severity Index (EASI).

  13. 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)

    Scoring of areas of involvement in each anatomical region (area), calculation of intensity using Patient oriented eczema measure (POEM).

  14. 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)

    Changes in the extent (%) and severity of skin lesions and their complications (i.e. infections, atrophy, itching) using Psoriasis Area and Severity Index (PASI).

  15. 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)

    Changes in the extent (%) and severity of skin lesions and their complications (i.e. infections, atrophy, itching) using Modified Total Lesional Sign Score (MTLSS).

  16. 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)

    Biophysical Skin Evaluation: Skin measurement of transepidermal water loss to monitor skin barrier function and erythema

  17. 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)

    Measurement of the number of red blood cells (Complete Blood Counts with Differential [CBCD]).

  18. 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)

    Measurement of the number of reticulocytes.

  19. 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)

    Measure the number of platelets (Complete Blood Counts with Differential (CBCD)).

  20. 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)

    Measure the number of neutrophils (Complete Blood Counts with Differential [CBCD]).

  21. 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).

  22. 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).

  23. 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);

    Mean daily insulin use recorded over 7 consecutive days preceding each evaluation timepoint for patients with Type 1 Diabetes.

  24. 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);

    Continuous glucose monitoring (CGM) metrics to log episodes of hyper/hypoglycemic events.

  25. Change in Autoantibody Profile

    Time frame: Screening/ Baseline, Post-infusion (Month 6 and 12)

    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

  26. 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

    Measure kidney functional parameters, i.e., creatinine, in the blood and urine.

  27. Change in PedsQL General Well-Being Scale - Quality of Life

    Time frame: Pre-Infusion; Month 6, 12

  28. Change in PedsQL Generic Core Scale - Quality of Life

    Time frame: Pre-Infusion; Month 6, 12

  29. Change in PedsQL Gastrointestinal Symptoms Scale - Quality of Life

    Time frame: Pre-Infusion; Month 6, 12

    Measured with Gastrointestinal Symptoms Scale: minimum value = 0 (never a problem), maximum value = 4 (almost always a problem). Higher scores mean a worse outcome.

  30. Disease-free Survival - Changes from Baseline

    Time frame: Up to 15 years

    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.

  31. Overall Survival - Changes from Baseline

    Time frame: Up to 15 years

    Participant survival

Study contacts

Contact information is provided by the study sponsor or research team.

Rosa Bacchetta, MD

CONTACT

[email protected]

650-498-8369

Sponsors and collaborators

Lead sponsor

Bacchetta, Rosa, MD

Other

Collaborators

  • California Institute for Regenerative Medicine (CIRM)

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2027
Study completion
2037
First posted
Feb 15, 2022
Registry last updated
May 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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