Study to evaluate the effect and the safety of ladaraxin in adult and adolescent patients with recent onset type 1 diabetes
- Conditions
- Recent onset Type 1 Diabetes
- Registration Number
- 2024-513560-26-00
- Lead Sponsor
- Dompe' Farmaceutici S.p.A.
- Brief Summary
The objective of this clinical trial is to assess whether ladarixin treatment has an effect to preserve Beta-cell function and delay the progression of T1D in adolescent and adult patients. The safety of ladarixin in the specific clinical setting will be also evaluated.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruitment ended
- Sex
- Not specified
- Target Recruitment
- 103
Male and female patients aged 14-45 years, inclusive;
Recent onset T1D (1st IMP dose within 180 days from 1st insulin administration);
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);
Require, or has required at some time insulin therapy through one or more separate subcutaneous injections or Continuous Subcutaneous Insulin Infusion (CSII).
Fasting C peptide < 0.205nmol/L
Residual β-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
Patient able to comply with all protocol procedures for the duration of the study, including scheduled follow-up visits and examinations
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.
A type 2 diabetes diagnosis or any other unstable chronic disease for which dose adjustment of specific medication is anticipated during the trial
Previous (past 2 weeks) and concomitant treatment withantidiabetic agents as metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors, SGLT-2 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.)
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
Significant systemic infection during the 4 weeks before the 1st dose of study drug (e.g., infection requiring hospitalization, major surgery, or i.v. 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)
History of positive status for hepatitis A (IgM), hepatitis B (not due to immunization), hepatitis C and HIV
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 spermacide foam); abstinence.
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
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]
Hypoalbuminemia defined as serum albumin <3 g/dL
QTcF > 470 msec
Occurrence of an episode of ketoacidosis or hypoglycemic coma in the past 2 weeks
A history of significant cardiovascular disease/abnormality
Known hypersensitivity to non-steroidal anti-inflammatory drugs
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)]
Study & Design
- Study Type
- Not specified
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method - Change from baseline in 2-hour AUC of C-peptide response to the MMTT [Primary endpoint. Time frame: Month 6]. - Change from baseline in 2-hour AUC of C-peptide response to the MMTT [Primary endpoint. Time frame: Month 6].
- Secondary Outcome Measures
Name Time Method Change from baseline in 2-hour AUC of C-peptide response to the MMTT [Time frame: month 12, 18 and 24]. Change from baseline in 2-hour AUC of C-peptide response to the MMTT [Time frame: month 12, 18 and 24].
Change in HbA1c from baseline [Time frame: Month 6, 12, 18 and 24]. Change in HbA1c from baseline [Time frame: Month 6, 12, 18 and 24].
Time in range (TIR) by Continuous Glucose Monitoring (CGM) [Time frame: Month 6, 12, 18, 24]. Time in range (TIR) by Continuous Glucose Monitoring (CGM) [Time frame: Month 6, 12, 18, 24].
Proportion of patients with HbA1c <7% who did not experience severe hypoglycemic events during treatment [Time frame: Month 6, 12, 18 and 24]. Proportion of patients with HbA1c <7% who did not experience severe hypoglycemic events during treatment [Time frame: Month 6, 12, 18 and 24].
Average (previous 3 days) daily insulin requirement (IU/kg/day) [Time frame: Month 6, 12, 18 and 24]. Average (previous 3 days) daily insulin requirement (IU/kg/day) [Time frame: Month 6, 12, 18 and 24].
Proportion of patients with HbA1c <7% and daily insulin requirement <0.5 (IU/kg/day) [Time frame: Month 6, 12, 18 and 24]. Proportion of patients with HbA1c <7% and daily insulin requirement <0.5 (IU/kg/day) [Time frame: Month 6, 12, 18 and 24].
Additional Glucose Variability Indices derived from CGM (glucose AUC outside the target range of 70 – 180 mg/dL, 2-hour postprandial glucose (PPG), Mean Amplitude Glycemic Excursions (MAGE), continuous overall net glycemic action (CONGA)-n, Mean Of the Daily Differences (MODD), and mean daily blood glucose, SD (Standard Deviation). [Time frame: Month 6, 12, 18 and 24]. Additional Glucose Variability Indices derived from CGM (glucose AUC outside the target range of 70 – 180 mg/dL, 2-hour postprandial glucose (PPG), Mean Amplitude Glycemic Excursions (MAGE), continuous overall net glycemic action (CONGA)-n, Mean Of the Daily Differences (MODD), and mean daily blood glucose, SD (Standard Deviation). [Time frame: Month 6, 12, 18 and 24].
Number of self-reported episodes of severe hypoglycemia [Time frame: Month 6, 12, 18 and 24]. Number of self-reported episodes of severe hypoglycemia [Time frame: Month 6, 12, 18 and 24].
Percentage of patients not requiring insulin therapy [Time frame: Month 6, 12, 18 and 24] Percentage of patients not requiring insulin therapy [Time frame: Month 6, 12, 18 and 24]
Estimated Glucose Disposal Rate (eGDR) [Time frame: Month 6, 12, 18 and 24]. Estimated Glucose Disposal Rate (eGDR) [Time frame: Month 6, 12, 18 and 24].
Trial Locations
- Locations (13)
Universitair Ziekenhuis Brussel
🇧🇪Jette, Belgium
Diabetologikum DDG Ludwigshafe
🇩🇪Ludwigshafen, Germany
Universitaetsklinikum Giessen und Marburg GmbH
🇩🇪Giessen, Germany
Institut fuer Diabetesforschung Muenster GmbH
🇩🇪Muenster, Germany
Schwerpunktpraxis für Diabetes und Ernährungsmedizin
🇩🇪Germany
Medical Center - University Of Freiburg
🇩🇪Freiburg Im Breisgau, Germany
Universita' Campus Bio-medico Di Roma
🇮🇹Rome, Italy
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Ospedale Pediatrico Bambino Gesu
🇮🇹Rome, Italy
Azienda Ospedaliero-Universitaria Policlinico Umberto I
🇮🇹Rome, Italy
Scroll for more (3 remaining)Universitair Ziekenhuis Brussel🇧🇪Jette, BelgiumCorinne DebroyeSite contact+32473893478Corinne.debroye@uzbrussel.be