A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of 400 mg Twice a Day Oral Ladarixin in Patients With New-onset Type 1 Diabetes and Preserved Beta-cell Function at Baseline.

LDX0419

The objectives of this clinical trial are: * to evaluate whether a 12 month treatment with ladarixin is effective to improve glycemic control in newly diagnosed T1D adult patients with preserved beta-cell function. * to evaluate the safety of ladarixin in the specific clinical setting

2020-12-14

2023-04-27

2023-10-11

Terminated

Early phase I

25

Inclusion Criteria: 1. Male and female patients aged 18-45 years, inclusive; 2. New-onset T1D (1st IMP dose within 100 days from 1st insulin administration); 3. Positive for at least one diabetes-related auto-antibody (anti-GAD; IAA, if obtained within 10 days of the onset of insulin therapy; IA-2 antibody; ZnT8); 4. Require, or has required at some time, insulin therapy through multiple daily injections (MDI) or Continuous Subcutaneous Insulin Infusion (CSII); 5. Fasting C peptide ≥0.205nmol/L on two occasions; 6. Patient able to comply with all protocol procedures for the duration of the study, including scheduled follow-up visits and examinations; 7. Patients who have given written informed consent prior of any study-related procedure not part of standard medical care. Exclusion Criteria: 1. Any other chronic disease, including type 2 diabetes, apart from autoimmune hypothyroidism requiring thyroid hormone replacement only; patients with severe (myxedema) disease potentially requiring immunosuppressive therapy will be excluded; 2. Moderate to severe renal impairment as per estimated Glomerular Filtration Rate (eGFR) 60 mL/min/1.73 m2, as determined using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation (see Appendix 14.4.3); 3. Hepatic dysfunction defined by increased ALT/AST \> 3 x upper limit of normal (ULN) and increased total bilirubin \> 3 mg/dL \[\>51.3 μmol/L\]; 4. Hypoalbuminemia defined as serum albumin \< 3 g/dL; 5. QTcF \> 470 msec; 6. A history of significant cardiovascular disease/abnormality 7. Occurrence of an episode of ketoacidosis or hypoglycemic coma in the past 2 weeks; 8. Known hypersensitivity to non-steroidal anti-inflammatory drugs; 9. Concomitant treatment with drugs metabolized by CYP2C9 with a narrow therapeutic index \[i.e., phenytoin, warfarin, sulphanylurea hypoglycemics (e.g. tolbutamide, glipizide, glibenclamide/glyburide, glimepiride, nateglinide) and high dose of amitriptyline (\>50 mg/day)\]; 10. Previous (within 2 weeks prior to randomization) and concomitant treatment with antidiabetic agents as metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors, SGLT2-inhibitors or amylin, or any medications known to influence glucose tolerance (e.g. beta-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine antimalarial drugs, lithium, niacin, etc.); 11. Past (within 1 month prior to randomization) or current administration of any immunosuppressive medications (including oral, inhaled or systemically injected steroids) and use of any investigational agents, including any agents that impact the immune response or the cytokine system; 12. Significant systemic infection during the 4 weeks before the first dose of the study drug (e.g., infection requiring hospitalization, major surgery, or IV antibiotics to resolve; other infections, e.g., bronchitis, sinusitis, localized cellulitis, candidiasis, or urinary tract infections, must be assessed on a case-by-case basis by the investigator regarding whether they are serious enough to warrant exclusion); 13. Hepatitis A (IgM), hepatitis B (not due to immunization), hepatitis C and HIV positive serologic status Serologic evidence of current infectious liver disease (hepatitis A, B, or C), including ant hepatitis A virus (immunoglobulin M), hepatitis B surface antigen, or ant hepatitis C virus and HIV; 14. Pregnant or breast feeding women. Unwillingness to use effective contraceptive measures up to 2 months after the end of study drug administration (females and males). Effective contraceptive measures include a hormonal birth control (e.g. oral pills, long term injections, vaginal ring, patch); the intrauterine device (IUD); a double barrier method (e.g. condom or diaphragm plus spermicide foam).

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'Appearance, including packaging and labelling, of the IMP (capsules, packaging) will not allow to recognize actual treatment (either ladarixin or placebo).', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 25, 'type': 'ACTUAL'}}

2023-12-22