Efficacy and Safety of Ladarixin and Antithymocyte Globulin in Patients with New-Onset Autoimmune Type 1 Diabetes: A Phase 2b Randomized Controlled Trial
- Trial ID
- 2025-524298-18-00
- Protocol
- ATGLDX1-2025
- Sponsor
- Ospedale San Raffaele S.r.l.
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the efficacy of oral Ladarixin in combination with a single low dose of antithymocyte globulin by measuring changes in the stimulated C-peptide response during the first 2 hours of a mixed meal tolerance test at 12 months in adolescent and adult individuals with new-onset type 1 diabetes. The secondary objective involves determining the effects of Ladarixin treatment. This study assesses efficacy, safety, and dose response.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of adolescent and adult patients with Type 1 Diabetes. Eligible individuals must have a diagnosis confirmed by ADA Criteria within 180 days prior to randomization and must have required exogenous insulin. Participants are required to test positive for one or more diabetes-related autoantibodies, including GADA, IA-2A, ZnT8A, or IAA. Key inclusion requirements involve a body mass index of less than 30, a baseline HbA1c below 10%, and specific C-peptide levels measured via fasting or glucagon test depending on the duration of the diagnosis. The population includes both male and female subjects and is categorized as involving vulnerable groups. Participants must be able to comply with intensive standard of care diabetes management and adhere to specific restrictions regarding live immunization.
Plans and Procedures
This phase 2b, single-center, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of oral ladarixin in combination with a single low dose of antithymocyte globulin for patients with type 1 diabetes. Participants are randomized in a 1:1 ratio to receive either the test combination or antithymocyte globulin with a placebo. The research methodology involves an initial period of oral administration for 12 months, followed by intravenous infusions. The primary objective is to measure changes in the stimulated C-peptide response via a mixed meal tolerance test at the 12-month visit. Study procedures include a screening visit to confirm eligibility based on autoantibody presence, HbA1c levels, and C-peptide concentrations, followed by subsequent follow-up assessments to monitor secondary endpoints such as daily insulin requirements and glucose variability. The total duration of participant involvement is approximately 12 months of treatment. Early termination may occur based on clinical necessity or protocol non-compliance.
Treatment
Ladarixin is administered as an 800 mg dose in a hard capsule via the oral route.
Rabbit anti-human thymocyte immunoglobulin is administered via infusion at a dose of 1.0 mg/kg.
The placebo consists of microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, hydroxypropyl cellulose, citric acid monohydrate, and magnesium stearate.
Efficacy
The primary efficacy endpoint is the change from baseline in the area under the stimulated C-peptide curve (YAUC) at the 2-hour Mixed Meal Tolerance Test (MMTT) measured at the 12-month visit. Secondary endpoints include changes in fasting C-peptide, stimulated C-peptide, HbA1c, and daily insulin requirements throughout the study duration.
Efficacy is further assessed through glucose monitoring parameters, including:
- Time in range (70-180 mg/dl), time in tight range (70-140 mg/dl), and time below range (<70 mg/dl).
- Glucose management index and coefficient of variation (%CV) as measures of glucose variability via continuous glucose monitoring (CGM).
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Yet Recruiting | 15 Feb 2026 | 46 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Microcrystalline cellulose, Lactose
monohydrate, Croscarmellose Sodium,
Hydroxypropyl cellulose, Citric acid monohydrate,
Magnesium Stearate | Placebo | N/A | — | — | — | N/A |
RABBIT ANTI-HUMAN THYMOCYTE IMMUNOGLOBULIN | Test | — | INFUSION | 1.0 | 168 | SUB30326 |
Ladarixin | Test | CAPSULE, HARD | ORAL | 800 | 168 | PRD2793884 |