A phase 2b, single-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of oral Ladarixin in association with a single low dose of Antithymocyte Globulin in patients with new-onset autoimmune type 1 diabetes.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale San Raffaele S.r.l.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-04-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Breakthrough T1D; Dompé farmaceutici S.p.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response

To determine the changes in stimulated C-peptide response over the first 2 hours of a Mixed Meal Tolerance Test (MMTT) at 12 months for the ATG/LDX (Group A) versus ATG/placebo (Group B) in adolescent and adult individuals with new onset T1D.

Secondary objectives 1

1. To determine the effects of Ladarixin (LDX) treatment.

Conditions and MedDRA coding

new-onset autoimmune type 1 diabetes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1.For adults willingness to provide informed consent. For subjects 14 to 17 years of age provide written assent and have a parent or legal guardian provide informed consent. 2.Diagnosis of T1D based on ADA Criteria 3.A diagnosis of T1D for less than 180 days at randomization 4.Requires, or has required at some time, exogenous insulin between diagnosis and enrollment 5.Test positive for 1 or more diabetes-related autoantibody (GADA, IA-2A, ZnT8A, IAA) measured within 10 days of the start of insulin therapy and confirmed present at screening 6.Be willing to comply with intensive diabetes management (standard of care) 7.Will be ≥6 weeks from last live immunization at planned ATG infusion on day 1 and be willing to forgo live vaccines during the trial until 6 months post treatment 8.Patients <100 days from T1D diagnosis must have a fasting C-peptide at the screening visit >0.2 ng/mL. Patients ≥100 days from T1D diagnosis must have a stimulated C-peptide level (glucagon test) ≥0.6 ng/ml at the screening visit. Furthermore, to be eligible, the C-peptide at time 0’ of the MMTT at baseline must be ≥0.2 ng/ml 9.BMI < 30 10.Baseline HbA1c <10% (86 mmol/mol)

Exclusion criteria 1

1. 1. Be currently pregnant (urine pregnancy test) or lactating or anticipate getting pregnant within the study period. Women and men unwilling to use adequate contraception if sexually active during the study 2. Evidence of prior or current tuberculous or non-tuberculous mycobacterial infection 3. Immunodeficient or clinically significant chronic leucopenia, neutropenia, lymphopenia, or thrombo-cytopenia at the screening visit, according to local reference 4. Requiring use of other immunosuppressive or immunomodulation agents, including chronic use of systemic steroids 5. Evidence of renal dysfunction with creatinine greater than 1.5 times the ULN at screening, adjusted for the age of the patient 6. Evidence of liver dysfunction with AST or ALT greater than 3 times ULN, at screening 7. Clinically significant clotting disorder, according to local reference ranges. 8. Any active chronic infections at screening, or any active acute or chronic infections at baseline or on treatment day, which would contraindicate any immunosuppression 9. Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk to include pre-existing cardiac disease, COPD, sickle cell disease, neurological, or blood count abnormalities 10. Have a history of malignancies other than treated skin cancer 11. Ongoing use of non-insulin pharmaceuticals that affect glycemic control within 7 days prior to screening 12. Active participation in another T1D treatment interventional trial in the previous 30 days prior to screening 13. Any prior treatment with ATG, Abatacept or anti-CD3 antibodies 14. Known allergy to ATG or to related products, or hypersensitivity to rabbit proteins or to any of the excipients; known hypersensitivity to non-steroidal anti-inflammatory drugs, lactose intolerance 15. QTcF > 470 msec; Complete Left Bundle Branch Block (LBBB); atrio-ventricular block (Mobitz II 2nd degree or 2:1 atrio-ventricular block) 16. Any psychological or psychiatric conditions that may interfere with study procedures and treatments

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the study is the change from baseline in the area under the stimulated C-peptide curve (YAUC) at 2 hour MMTT conducted at the 12 month visit.

Secondary endpoints 1

1. Changes in: 1) fasting and stimulated C-peptide 2) HbA1c 3) daily insulin requirements throughout the study 4) time in range (70-180 mg/dl), time in tight range (70-140 mg/dl), time below range (<70 mg/dl), glucose management index by CGM and %CV as measure of glucose variability 5) QoL, patient treatment satisfaction and fear of hypoglycemia will be assessed using the Diabetes-Specific Quality of Life (DSQoL) Questionnaire and the FH-15 Questionnaire, both validated in Italian. 6) a

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale San Raffaele S.r.l.

Sponsor organisation

Ospedale San Raffaele S.r.l.

Address

Via Olgettina 60

City

Milan

Postcode

20132

Country

Italy

Scientific contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Clinical Trial Center

Public contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Clinical Trial Center

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 18 files

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

Application history

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