E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recent onset Type 1 Diabetes |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this clinical trial is to assess whether ladarixin treatment is effective in preserving Beta-cell function and delaying the progression of T1D in adolescent and adult patients. The safety of ladarixin in the specific clinical setting will be also evaluated. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Consented male and female patients aged 14-45 years, inclusive, with recent onset T1D (randomization scheduled to allow the administration of the study medication to start within 180 days from 1st insulin administration). Patients must be positive for at least one diabetesrelated auto-antibody (anti-GAD; IAA, if obtained within 10 days of the onset of insulin therapy; IA-2 antibody; ZnT8); must require, or have required insulin delivered via one or more separate subcutaneous injections or Continuous Subcutaneous Insulin Infusion (CSII); must have a fasting C-peptide below 0.205 nmol/L, but must retain a Beta-cell function as per peak stimulated (MMTT) C-peptide level >0.2 nmol/L. |
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E.4 | Principal exclusion criteria |
Patients will be excluded if they have a type 2 diabetes or any other unstable chronic disease for which dose adjustment of specific medication is anticipated during the trial; moderate to severe renal impairment calculated by estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73 m2 as determined using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation; hepatic dysfunction (increased ALT/AST >3 x upper limit of normal and increased total bilirubin >3 mg/dL [>51.3 μmol/L]); hypoalbuminemia (serum albumin <3 g/dL); a QTcF > 470 msec.; a history of significant cardiovascular disease/abnormality; occurrence of an episode of ketoacidosis or hypoglycemic coma in the past 2 weeks; a known hypersensitivity to non-steroidal anti-inflammatory drugs. Patients on treatment with drugs metabolized by CYP2C9 with a narrow therapeutic index [i.e. phenytoin, warfarin, sulphanylurea hypoglycemics and high dose of amitriptyline (>50 mg/day)]; patients with past (within 2 weeks prior to randomization) or current use of antidiabetic 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.) will also be excluded. Patients will be excluded as well in case of past (within 1 month prior to randomization) 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. Additional exclusion criteria will be: 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. Also, pregnant or breastfeeding women or patients unwilling to use effective contraceptive measures (females and males) will be excluded. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change from baseline in 2-hour AUC of C-peptide response to the MMTT [Primary endpoint. Time frame: Month 12]. - Change in HbA1c from baseline [Co-primary endpoint. Time frame: Month 12].
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At month 12; Month 12 = Week 52 + 2 weeks |
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E.5.2 | Secondary end point(s) |
- Change from baseline in 2-hour AUC of C-peptide response to the MMTT [Time frame: month 6, 18 and 24]. - Change in HbA1c from baseline [Time frame: Month 6, 18 and 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]. - 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) - 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]. - Estimated Glucose Disposal Rate (eGDR) [Time frame: Month 6, 12, 18 and 24].
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Month 6 = Week 26+2; Month 12 = Week 52+2; Month 18 = Week 78+2; Month 24 = Week 104+2 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Georgia |
Israel |
Serbia |
United States |
Belgium |
Germany |
Italy |
Slovenia |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For the purpose of this trial, the End of Study is defined as the date of the last visit of the last patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |