new onset type 1 diabetes MedDRA version: 18.0 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders MedDRA version: 18.0 Level: LLT Classification code 10012608 Term: Diabetes mellitus insulin-dependent System Organ Class: 10027433 - Metabolism and nutr
Conditions
Interventions
Product Name: LADARIXIN
Product Code: DF 2156A
Pharmaceutical Form: Capsule
INN or Proposed INN: Ladarixin (formerly Meraxin)
CAS Number
Sponsors
Dompé farmaceutici s.p.a.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male and female patients aged 18-45 years, inclusive; 2.New-onset T1D (randomization 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, with the exclusion of patients taking twice daily pre-mixed insulin or on insulin pump; 5.Residual ß-cell function as per peak stimulated (MMTT) C-peptide level >0.6ng/mL (0.2nmol/L); MMTT should not be performed within one week of resolution of a diabetic ketoacidosis event; 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; Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 72 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Patients taking twice daily pre-mixed insulin or on insulin pump 2.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; 3.Moderate to severe renal impairment as per calculated creatinine clearance (CLcr) 3 x upper limit of normal (ULN) and increased total bilirubin > 3 mg/dL [>51.3 µmol/L]; 5.Hypoalbuminemia defined as serum albumin 470 msec; 7.Complete Left Bundle Branch Block (LBBB), atrio-ventricular block (mobitz II 2nd degree or 2:1 atrio-ventricular block), complete heart block; 8.Electronic pacemaker positioned or implanted defibrillator; 9.History of significant cardiovascular disease; 10.Known hypersensitivity to non-steroidal antiinflammatory drugs; 11.Concomitant treatment with phenytoin, warfarin, sulphanylurea hypoglycemics (e.g. tolbutamide, glipizide, glibenclamide/glyburide, glimepiride, nateglinide) and high dose of amitriptyline (> 50 mg/day); 12.Previous (within 2 weeks prior to randomization) and concomitant treatment with metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin, or any medications known to influence glucose tolerance (e.g. ß-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine antimalarial drugs, lithium, niacin, etc.); 13.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; 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this clinical trial is to investigate whether ladarixin has sufficient activity (preservation ofß-cell function and slow-down of the progression of T1D) to warrant its further development (proof of concept trial). ;Secondary Objective: The safety of ladarixin in the specific clinical setting will be also evaluated. ; Primary end point(s): Efficacy endpoint 2-hour area under the curve (AUC) of C-peptide response to a Mixed Meal Tolerance Test (MMTT) ;Timepoint(s) of evaluation of this end point: baseline, week 13±1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: already detailed above; Secondary end point(s): 2-hour AUC of C-peptide response to the MMTT [Time frame: baseline, weeks 26±2 and 52±2]. -Average (previous 3 days) insulin requirements (IU/kg/day) [Time frame: baseline, weeks 13±1, 26±2 and 52±2]. -HbA1c levels [Time frame: baseline, weeks 13±1, 26±2 and 52±2]. -Basal (2 basal samples in the range between -20 to 0 min) to 180 min time course of C-peptide and glucose derived from the MMTT [Time frame: baseline, weeks 13±1, 26±2 and 52±2]. -Cumulative severe hypoglycaemic events occurring from randomization [Time frame: weeks 13±1, 26±2 and 52±2]. Exploratory endpoints will be: -Basal (2 basal samples in the range between -20 to 0 min) to 180 min time course of glucagon derived from the MMTT [Time frame: baseline, weeks 13±1, 26±2 and 52±2]. -Auto-antibodies (GAD, IA-2, IAA, ZnT8) [Time frame: baseline, weeks 13±1, 26±2 and 52±2]. -MicroRNA-375 (miR-375) [Time frame: baseline, weeks 13±1, 26±2 and 52±2]. -T-cell response ex vivo to major ß-cell antigens (pro-insulin, GAD65) - selected sites only [Time frame: baseline, weeks 13±1, 26±2 and 52±2]. Safety endpoints will be: -Vital signs (blood pressure and heart rate) [time frame: screening, end of 1st treatment cycle (i.e. pre-dose visit, 2nd cycle), week 13±1]. -Routine laboratory tests (haematology, clinical chemistry) [time frame: screening, end of 1st treatment cycle (i.e. pre-dose visit, 2nd cycle), weeks 13±1 (or withdrawal)]. -Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [time frame: throughout the study]. | — |
Countries
Belgium, Germany, Italy
Contacts
Public ContactMedical Associate Director
Dompé Inc.
Outcome results
None listed