Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess Efficacy - Safety of 400 mg Twice a Day Oral Ladarixin in Pts With New-onset Type 1 Diabetes and Low Residual β-cell Function at Baseline (GLADIATOR STUDY)
The objective of this clinical trial is to assess whether ladarixin treatment is effective in preserving beta-cell function and delaying the progression of type 1 diabetes (T1D) in adolescent and adult patients. The safety of ladarixin in the specific clinical setting will be also evaluated.
The study is planned to be performed at about 40 study centers in EU, US and in other countries, if appropriated. At each study center, the Principal Investigator (PI) will be responsible for ensuring that the investigation is conducted according to the signed Investigator agreement, the protocol, GCP guidelines, and local regulations.
The study is planned to involve -327 patients with new-onset T1D, to include about 200 adolescents (14-17 years). Patients will be randomly (2:1) assigned to receive either ladarixin treatment (400 mg b.i.d. for 13 cycles of 14 days on/14 days off - treatment group) or matched placebo (control group). The two groups will be balanced within centers.
14 Years to 45 Years
Accepting Healthy Volunteers?
1. Male and female patients aged 14-45 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;
6. Residual beta-cell function as per peak stimulated (MMTT) C-peptide level >0.2nmol/L; MMTT should not be performed within one week of resolution of a diabetic ketoacidosis event;
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/1.73m2, 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. Occurrence of an episode of ketoacidosis or hypoglycemic coma in the past 2 weeks;
7. A history of significant cardiovascular disease/abnormality;
8. Known hypersensitivity to non-steroidal anti-inflammatory drugs;