CLINICAL TRIAL / NCT04628481
A Study of Oral Ladarixin in Recent Onset Type 1 Diabetes and a Low Residual β-cell Function
- Interventional
- Recruiting
- NCT04628481
Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess Efficacy - Safety of 400 mg Twice a Day Oral Ladarixin in Pts With Recent 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.
This is a phase 3, multicenter, double-blind, placebo-controlled study. It has been designed
to further evaluate whether ladarixin is effective in preserving beta-cell function and
slowing-down the progression of T1D) in patients with a more severe disease presentation.
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.
Gender
All
Age Group
14 Years to 45 Years
Accepting Healthy Volunteers
No
Inclusion Criteria:
1. Male and female patients aged 14-45 years, inclusive;
2. Recent onset T1D (1st IMP dose within 180 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 one or more separate
subcutaneous injections 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;
7. Patient able to comply with all protocol procedures for the duration of the study,
including scheduled follow-up visits and examinations;
8. Patients who have given written informed consent prior of any study-related procedure
not part of standard medical care (participants under the age of 18, shall provide an
assent for the study as per country requirements). Specific consent must be given by
adolescents to be selected for the full PK analysis.
Exclusion Criteria:
1. A type 2 diabetes diagnosis or any other unstable chronic disease for which dose
adjustment of specific medication is anticipated during the trial;
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;
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 amitriptyline (> 50
mg/day)];
10. Previous (past 2 weeks) 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 (past month) or current administration of any immunosuppressive medications
(including oral or systemic corticosteroids) 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 1st 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. History of positive status for hepatitis A (IgM), hepatitis B (not due to
immunization), hepatitis C 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); abstinence.