IMMUNOSTEM for Type 1 diabetes mellitus

Inclusion criteria

• {"criterion_text":"- 1.\tCapable of giving signed informed consent as described in Section 13.2, which includes compliance with the requirements and restrictions listed in the Informed Consent Form and this protocol."}
• {"criterion_text":"- 2.\tMale or female patients."}
• {"criterion_text":"- 3.\tAge ≥18 and ≤40 years (≤25 years at Padova University Hospital due to feasibility constraints of the phase I clinical centre)."}
• {"criterion_text":"- 4.\tPatient able to comply with all protocol procedures for the duration of the study."}
• {"criterion_text":"- 5.\tRecent T1D onset/diagnosis (patients should receive the DP within 180 days from the 1st insulin administration)."}
• {"criterion_text":"- 6.\tHbA1c ≥53 and ≤150 mmol/mol."}
• {"criterion_text":"- 7.\tPositivity to at least 2 autoantibodies (i.e., anti-insulin, IAA; anti-glutamic acid decarboxylase 65, GAD65; anti-islet antigen 2, IA-2A; anti-zinc transporter 8, ZnT8; anti-islet cell antibody, ICA)."}
• {"criterion_text":"- 8.\tBasal C-peptide levels ≥0.2 nmol/L or ≥0.6 ng/mL; if basal C-peptide levels <0.2 nmol/L, stimulated C-peptide peak ≥0.2 nmol/L or ≥0.6 ng/mL during a 2-hour MMTT; MMTT should not be performed within one week of resolution of a diabetic ketoacidosis event."}

Exclusion criteria

• {"criterion_text":"- 1.\tUnwillingness to sign the informed consent."}
• {"criterion_text":"- 3.\tAny other unstable chronic disease."}
• {"criterion_text":"- 4.\tSignificant systemic infection during the four weeks before requiring hospitalisation, administration of intravenous antibiotics, surgery."}
• {"criterion_text":"- 5.\tPresent administration of anti-neoplastic drugs."}
• {"criterion_text":"- 6.\tQTcF >470 msec."}
• {"criterion_text":"- 7.\tOccurrence of an episode of ketoacidosis or hypoglycaemic coma in the past two weeks."}
• {"criterion_text":"- 8.\tPresence of a ≥grade 3 adverse event (including laboratory analyses) according to CTCAE version 5.0."}
• {"criterion_text":"- 9.\tEvidence of clinically significant abnormalities at bone-marrow aspirate."}
• {"criterion_text":"- 12. Active CMV or EBV infection, defined as EBV DNA or CMV DNA >1,000 copies/mL."}
• {"criterion_text":"- 10.\tBody Mass Index (body weight*height2)>27 kg⁄m2."}
• {"criterion_text":"- 11.\tA positive result to Biological Screening testing for Anti-HCV Antibody (Ab), HCV nucleic acid test (NAT) (if anti-HCV Ab positive), HIV-1/-2 p24 Ab and antigen (Ag), HIV RNA NAT, anti-Treponema pallidum total Ig, HbsAg (Australia Ag), HBV DNA NAT, total anti-HB core Ab (if HBV DNA NAT positive), anti-HTLV I, and anti-HTLV II (if applicable)."}
• {"criterion_text":"- 13.\tActive SARS-CoV-2 infection."}
• {"criterion_text":"- 14.\tAllergy to mobilizing agents (G-CSF and plerixafor)."}
• {"criterion_text":"- 15.\tPregnancy or lactation."}
• {"criterion_text":"- 16.\tAbsence of an efficacious method of contraception."}
• {"criterion_text":"- 17.\tAny condition that in the opinion of investigator contraindicates apheresis or infusion of transduced HSPCs or affects patient’s compliance."}
• {"criterion_text":"- 2.\tType 2 diabetes."}

Primary endpoints

• {"endpoint_text":"- Primary endpoint will be the evaluation of safety of the study treatment, including number and description of adverse events at endpoint based on vital signs, laboratory tests, frequency and severity of AEs and serious AEs. Safety parameters will be assessed over the first 3, 12 and 24 months of follow up in the patients enrolled during the pilot phase. In case of positive evaluation of safety results of the pilot phase at the 3 month assessment by the DSMB, the study will continue with the enro","definition_or_measurement_approach":"Evaluation of safety via number and description of adverse events based on vital signs, laboratory tests, frequency and severity of AEs and serious AEs; safety assessed at 3, 12 and 24 months of follow-up in pilot phase; continuation decision at 3-month DSMB assessment."}

Secondary endpoints

• {"endpoint_text":"- Changes over time of the 3-hour area under curve (AUC) and ΔAUC normalised by baseline glucose blood levels of C-peptide response to a mixed meal tolerance test (MMTT) over 12 and 24 months.","definition_or_measurement_approach":"3-hour AUC and ΔAUC of C-peptide response to MMTT, normalized by baseline glucose, assessed over 12 and 24 months."}
• {"endpoint_text":"- Changes of glucose metrics from continuous glucose monitoring over 12 and 24 months, including: -Time in glycaemic target range expressed as a daily average of the percentage of time in a 24 hour-day a participant's blood glucose is >70 but ≤180 mg/dL (>3.9 to ≤10.0 mmol/L) during the previous 14 days -Time in tight range (70-140 mg/dL) during the previous 14 days -Time above range (180-250 and >250 mg/dL) during the previous 14 days -Time below range (level 1: 54-70 and level 2: <54 mg/dL).","definition_or_measurement_approach":"Continuous glucose monitoring (CGM) metrics over 14-day windows, reported as time in range (70-180 mg/dL), time in tight range (70-140 mg/dL), time above range (180-250 and >250 mg/dL), and time below range (level 1 and 2). Assessed over 12 and 24 months."}
• {"endpoint_text":"- Exogenous insulin requirement defined as a daily average in units per kilogram per day (U/kg/day) during the previous 14 days.","definition_or_measurement_approach":"Daily average insulin use (U/kg/day) calculated over prior 14 days."}
• {"endpoint_text":"- Changes and trend analysis of HbA1c levels over 12 and 24 months.","definition_or_measurement_approach":"Serial HbA1c measurements with trend analysis at 12 and 24 months."}
• {"endpoint_text":"- Number of self-reported episodes of severe (CTCAE version 5.0 grade 3) hypoglycaemia.","definition_or_measurement_approach":"Count of self-reported severe hypoglycaemia episodes categorized as CTCAE v5.0 grade 3."}
• {"endpoint_text":"- Longitudinal analysis of vector copy number (VCN) in peripheral blood samples to assess frequency and persistence of infused cells and their progenies.","definition_or_measurement_approach":"Serial measurement of vector copy number (VCN) in peripheral blood over time to evaluate persistence and frequency of infused cells."}
• {"endpoint_text":"- In case of VCN>the limit of quantification, execution of vector insertion site analysis (VISA).","definition_or_measurement_approach":"Perform vector insertion site analysis (VISA) when VCN exceeds limit of quantification."}
• {"endpoint_text":"- Exploratory endpoints: Estimated Glucose Disposal Rate (eGDR); Changes in autoantibody titres (including but not limited to): Anti-insulin (anti-IAA), Anti-glutamic acid decarboxylase 65 (anti-GAD65), Anti-islet antigen 2 (anti-IA-2A), Anti-Zinc transporter 8 (anti-ZnT8), Anti-islet cell antibody (anti-ICA); Correlation between VCN and CGM-derived glucose; Changes in extended immunophenotype analyses including NK, B and T cells, T cell subpopulations, T regulatory cells (including FOXP3+ cells).","definition_or_measurement_approach":"Exploratory assessments including eGDR, autoantibody titre changes, correlation analyses between VCN and CGM metrics, and extended immunophenotyping of NK, B, T cells and regulatory T cell populations."}

Italy

Earliest CTIS Part Ii Submission Date

04-07-2025

Latest Decision Or Authorization Date

30-09-2025

Processing Time Days

88

Number Of Sites

1

Number Of Participants

15

Primary sponsor

Full Name

Altheia Science S.r.l.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Evidenze Health S.r.l.","duties_or_roles":[1,12,14,5],"organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Evidenze Health Espana S.L.","duties_or_roles":[10,11,6,7,8],"organisation_type":"Pharmaceutical company"}