CD4^LVFOXP3 bei Teilnehmern mit IPEX
2. November 2026 aktualisiert von: Jessie L. Alexander, MD, Bacchetta, Rosa, MD
Phase-1-Studie zu autologem CD4^LVFOXP3 bei Teilnehmern mit Immundysregulations-Polyendokrinopathie-Enteropathie-X-chromosomalem (IPEX)-Syndrom
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.
Studienübersicht
Detaillierte Beschreibung
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.
Studientyp
Interventionell
Einschreibung (Tatsächlich)
16
Phase
- Phase 1
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
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California
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Palo Alto, California, Vereinigte Staaten, 94305
- Lucile Packard Children's Hospital
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
4 Monate bis 35 Jahre (Kind, Erwachsene)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Männlich
Beschreibung
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
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Sequenzielle Zuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: Cohort A (≥12 years)
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. |
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.
Andere Namen:
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Experimental: Cohort B (<12 years)
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. |
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.
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Meet target cell number for dose manufacturing
Zeitfenster: Time at release from manufacturing (by Day 0 [infusion day] for each participant)
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No more than two products fail the target cell dose and established release criteria. |
Time at release from manufacturing (by Day 0 [infusion day] for each participant)
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Find the safe maximum tolerated dose
Zeitfenster: Up to 60 days post-infusion for each participant
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No more than 1 out of 6 participants may experience a related dose limiting toxicity or treatment emergent adverse events. |
Up to 60 days post-infusion for each participant
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Veränderung der altersspezifischen Perzentile der Körpergröße
Zeitfenster: Baseline (bis zu 60 Tage vor der Infusion von CD4^LVFOXP3) bis nach der Infusion (Monat 12)
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Baseline (bis zu 60 Tage vor der Infusion von CD4^LVFOXP3) bis nach der Infusion (Monat 12)
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Veränderung der altersspezifischen Perzentile des Körpergewichts
Zeitfenster: Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 1, 2, 3, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9, 12)
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Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 1, 2, 3, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9, 12)
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Veränderung des Bilirubinspiegels
Zeitfenster: Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 2, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9 und 12)
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Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 2, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9 und 12)
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Veränderung des Leberenzyms - Alanin-Transaminase (ALT)
Zeitfenster: Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 2, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9 und 12)
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Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 2, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9 und 12)
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Veränderung des Leberenzyms - Aspartat-Transaminase (AST)
Zeitfenster: Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 2, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9 und 12)
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Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 2, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9 und 12)
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Veränderung des Leberenzyms - Alkalische Phosphatase (ALP)
Zeitfenster: Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 2, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9 und 12)
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Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 2, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9 und 12)
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Veränderung des Leberenzyms - Gamma-Glutyltranspeptidase (GGT)
Zeitfenster: Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 2, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9 und 12)
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Baseline (bis zu 60 Tage vor Infusion von CD4^LVFOXP3), Präinfusion bis Postinfusion (Tag 2, Woche 1, 2, 3, 4; Monat 2, 3, 6, 9 und 12)
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Veränderung des C-Peptids – Typ-1-Diabetes Prämanifestation
Zeitfenster: Baseline 60–30 Tage vor der Infusion von CD4^LVFOXP3; Nach der Infusion (Woche 4, Monat 3, 6 und 12).
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Baseline 60–30 Tage vor der Infusion von CD4^LVFOXP3; Nach der Infusion (Woche 4, Monat 3, 6 und 12).
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Veränderung des HbA1c - Typ-1-Diabetes Vor Beginn
Zeitfenster: Baseline 60–30 Tage vor der Infusion von CD4^LVFOXP3; Nach der Infusion (Woche 4, Monat 3, 6 und 12).
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Baseline 60–30 Tage vor der Infusion von CD4^LVFOXP3; Nach der Infusion (Woche 4, Monat 3, 6 und 12).
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Änderung der PedsQL-Skala für allgemeines Wohlbefinden – Lebensqualität
Zeitfenster: Vorinfusion; Monat 6, 12
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Vorinfusion; Monat 6, 12
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Änderung der generischen PedsQL-Kernskala – Lebensqualität
Zeitfenster: Vorinfusion; Monat 6, 12
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Vorinfusion; Monat 6, 12
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Change in Diarrhea incidence
Zeitfenster: 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)
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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). |
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)
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Change in GI Symptoms - Gastrointestinal Symptoms Rating Scale
Zeitfenster: Baseline (up to 60 days before infusion of CD4^LVFOXP3) through post-infusion (Week 4, Month 6, Month 12)
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Gastrointestinal Symptoms Rating Scale (GSRS) (for patients ≥12 years old). |
Baseline (up to 60 days before infusion of CD4^LVFOXP3) through post-infusion (Week 4, Month 6, Month 12)
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Change in Body Mass Index (BMI)
Zeitfenster: 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)
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BMI measured as kg/m^2. |
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)
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Change in INR level
Zeitfenster: Baseline/screening (up to 60 days before infusion of CD4^LVFOXP3) through post-infusion (Week 4; Month 3, 6, 12)
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International normalized ratio (INR) to determine prothrombin time. |
Baseline/screening (up to 60 days before infusion of CD4^LVFOXP3) through post-infusion (Week 4; Month 3, 6, 12)
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Skin Disease (EASI) - Changes from Baseline/ Pre-infusion
Zeitfenster: 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)
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Scoring of areas of involvement in each anatomical region (area), calculation of intensity using Eczema Area and Severity Index (EASI). |
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)
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Skin Disease (POEM) - Changes from Baseline/ Pre-infusion
Zeitfenster: 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)
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Scoring of areas of involvement in each anatomical region (area), calculation of intensity using Patient oriented eczema measure (POEM). |
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)
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Skin Disease (PASI) - Changes from Baseline/ Pre-infusion
Zeitfenster: 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)
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Changes in the extent (%) and severity of skin lesions and their complications (i.e. infections, atrophy, itching) using Psoriasis Area and Severity Index (PASI). |
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)
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Skin Disease (MTLSS) - Changes from Baseline/ Pre-infusion
Zeitfenster: 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)
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Changes in the extent (%) and severity of skin lesions and their complications (i.e. infections, atrophy, itching) using Modified Total Lesional Sign Score (MTLSS). |
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)
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Change in skin barrier function
Zeitfenster: 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)
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Biophysical Skin Evaluation: Skin measurement of transepidermal water loss to monitor skin barrier function and erythema |
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)
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Change in Hemolytic Anemia (RBC)
Zeitfenster: 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)
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Measurement of the number of red blood cells (Complete Blood Counts with Differential [CBCD]). |
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)
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Change in Hemolytic Anemia (Reticulocyte)
Zeitfenster: 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)
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Measurement of the number of reticulocytes. |
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)
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Change in Thrombocytopenia
Zeitfenster: 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)
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Measure the number of platelets (Complete Blood Counts with Differential (CBCD)). |
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)
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Change in Neutropenia
Zeitfenster: 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)
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Measure the number of neutrophils (Complete Blood Counts with Differential [CBCD]). |
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)
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Change in Daily insulin requirement - Type 1 diabetes monitoring
Zeitfenster: Baseline taken 60-30 days before infusion of CD4^LVFOXP3 and post-infusion (over 7 consecutive days preceding each study visit);
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Mean daily insulin use recorded over 7 consecutive days preceding each evaluation timepoint for patients with Type 1 Diabetes. |
Baseline taken 60-30 days before infusion of CD4^LVFOXP3 and post-infusion (over 7 consecutive days preceding each study visit);
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Change in hyper-/hypo-glycemic events - Type 1 diabetes monitoring
Zeitfenster: Baseline taken 60-30 days before infusion of CD4^LVFOXP3 and post-infusion (over 7 consecutive days preceding each study visit);
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Continuous glucose monitoring (CGM) metrics to log episodes of hyper/hypoglycemic events. |
Baseline taken 60-30 days before infusion of CD4^LVFOXP3 and post-infusion (over 7 consecutive days preceding each study visit);
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Change in Autoantibody Profile
Zeitfenster: Screening/ Baseline, Post-infusion (Month 6 and 12)
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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 |
Screening/ Baseline, Post-infusion (Month 6 and 12)
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Change in Creatinine as a measure of Kidney Function
Zeitfenster: Baseline taken 60-30 days before infusion of CD4^LVFOXP3, Pre-infusion, Week 1, 2, 3, 4; Month 2, 3, 6, 9 and 12
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Measure kidney functional parameters, i.e., creatinine, in the blood and urine. |
Baseline taken 60-30 days before infusion of CD4^LVFOXP3, Pre-infusion, Week 1, 2, 3, 4; Month 2, 3, 6, 9 and 12
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Change in PedsQL Gastrointestinal Symptoms Scale - Quality of Life
Zeitfenster: Pre-Infusion; Month 6, 12
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Measured with Gastrointestinal Symptoms Scale: minimum value = 0 (never a problem), maximum value = 4 (almost always a problem). Higher scores mean a worse outcome. |
Pre-Infusion; Month 6, 12
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Disease-free Survival - Changes from Baseline
Zeitfenster: Up to 15 years
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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. |
Up to 15 years
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Overall Survival - Changes from Baseline
Zeitfenster: Up to 15 years
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Participant survival |
Up to 15 years
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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Mitarbeiter
Ermittler
- Hauptermittler: Jessie Alexander, MD, Stanford University
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
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Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
22. März 2022
Primärer Abschluss (Geschätzt)
1. Dezember 2026
Studienabschluss (Geschätzt)
1. Oktober 2027
Studienanmeldedaten
Zuerst eingereicht
12. Januar 2022
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
4. Februar 2022
Zuerst gepostet (Tatsächlich)
15. Februar 2022
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
5. November 2026
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
2. November 2026
Zuletzt verifiziert
1. November 2026
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- IRB-63373
- DRU-2020-7764 (Andere Kennung: FDA Office of Orphan Products Development)
- RPD-2020-470 (Andere Kennung: FDA Office of Orphan Products Development)
- CLIN2-13259 (Andere Zuschuss-/Finanzierungsnummer: California Institute of Regenerative Medicine (CIRM))
- 1R01FD007540 (US-FDA-Zuschuss/Vertrag)
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Ja
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Nein
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