CD4^LVFOXP3 in Participants With IPEX

ConditionIPEX
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexMale
Age4-35
SponsorBacchetta, Rosa, MD

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • CD4^LVFOXP3

    Biological/Vaccine

    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.

Treatment groups

30 Participants
are divided into 2 treatment groups
Group A: Cohort A (≥12 years)Experimental treatment 1 intervention
Group B: Cohort B (<12 years)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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)
2

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

Secondary outcomes

1

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)
2

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)
3

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)
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)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Bacchetta, Rosa, MD

Lead sponsor

Stanford University

Sponsor institution

California Institute for Regenerative Medicine (CIRM)

Collaborator