A first-in-human clinical trial using a gene therapy with patient’s own stem cells to treat early type 1 diabetes

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Altheia Science S.r.l.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

13 Mar 2026 → ongoing

Decision date (initial)

2025-09-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Altheia Science S.r.l.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Therapy, Safety

The primary objective of the clinical trial is to evaluate study treatment safety.

Secondary objectives 3

1. To evaluate participant improvements in key clinical parameters of diabetes management.
2. To assess pharmacodynamic parameters.
3. Exploratory Objectives: To assess immunologic and other pharmacodynamic parameters.

Conditions and MedDRA coding

Type 1 diabetes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Capable 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.
2. 2. Male or female patients.
3. 3. Age ≥18 and ≤40 years (≤25 years at Padova University Hospital due to feasibility constraints of the phase I clinical centre).
4. 4. Patient able to comply with all protocol procedures for the duration of the study.
5. 5. Recent T1D onset/diagnosis (patients should receive the DP within 180 days from the 1st insulin administration).
6. 6. HbA1c ≥53 and ≤150 mmol/mol.
7. 7. Positivity 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).
8. 8. Basal 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 17

1. 1. Unwillingness to sign the informed consent.
2. 10. Body Mass Index (body weight*height2)>27 kg⁄m2.
3. 11. A 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).
4. 13. Active SARS-CoV-2 infection.
5. 14. Allergy to mobilizing agents (G-CSF and plerixafor).
6. 15. Pregnancy or lactation.
7. 16. Absence of an efficacious method of contraception.
8. 17. Any condition that in the opinion of investigator contraindicates apheresis or infusion of transduced HSPCs or affects patient’s compliance.
9. 2. Type 2 diabetes.
10. 3. Any other unstable chronic disease.
11. 4. Significant systemic infection during the four weeks before requiring hospitalisation, administration of intravenous antibiotics, surgery.
12. 5. Present administration of anti-neoplastic drugs.
13. 6. QTcF >470 msec.
14. 7. Occurrence of an episode of ketoacidosis or hypoglycaemic coma in the past two weeks.
15. 8. Presence of a ≥grade 3 adverse event (including laboratory analyses) according to CTCAE version 5.0.
16. 9. Evidence of clinically significant abnormalities at bone-marrow aspirate.
17. 12. Active CMV or EBV infection, defined as EBV DNA or CMV DNA >1,000 copies/mL.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 8

1. 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.
2. 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).
3. Exogenous insulin requirement defined as a daily average in units per kilogram per day (U/kg/day) during the previous 14 days.
4. Changes and trend analysis of HbA1c levels over 12 and 24 months.
5. Number of self-reported episodes of severe (CTCAE version 5.0 grade 3) hypoglycaemia.
6. Longitudinal analysis of vector copy number (VCN) in peripheral blood samples to assess frequency and persistence of infused cells and their progenies.
7. In case of VCN>the limit of quantification, execution of vector insertion site analysis (VISA).
8. 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).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Altheia Science S.r.l.

Sponsor organisation

Altheia Science S.r.l.

Address

Via Conservatorio 30

City

Milan

Postcode

20122

Country

Italy

Scientific contact point

Organisation

Altheia Science S.r.l.

Contact name

Gian Paolo Maria Rizzardi

Public contact point

Organisation

Altheia Science S.r.l.

Contact name

Gian Paolo Maria Rizzardi

Third parties 2

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications