A Study of Oral Ladarixin in Recent Onset Type 1 Diabetes and a Low Residual β-cell Function

Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess Effect and Safety of 400 mg Twice a Day Oral Ladarixin in Patients With Recent Onset Type 1 Diabetes and Low Residual β-cell Function at Baseline (GLADIATOR)

Objectives The objective of this clinical trial is to assess whether ladarixin treatment has an effect to preserve β-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.

Study Overview

• Status: Terminated
• Conditions: Recent Onset type1 Diabetes
• Intervention / Treatment: Drug: Ladarixin; Drug: Placebo

Detailed Description

The study will be a phase 2, multicenter, double-blind, placebo-controlled study. It will randomize approximately 130-140 patients (with up to an estimated 15-20% adolescents), with recent onset (within 180 days from 1st insulin administration) type 1 diabetes (T1D), assigned (2:1) to receive either oral ladarixin treatment (400 mg b.i.d. for 13 cycles of 14 days on/14 days off - treatment group) or placebo (control group). Recruitment will be competitive among the study sites, until the planned number of patients is randomized.

Ladarixin and placebo will be both administered for 1 year. All patients will be followed-up for 24 months from the 1st administration of the study medication. After the initial 12-m treatment period, all patients will enter into a 12-month follow-up (total period 24-month after first IMP administration). The study database (DB) will be locked when the last randomized patient has completed the month 12 visit (or being lost in follow-up), and relative data have been fully reconciled and cleaned; at that point, the DB will be unblinded and all endpoints, including the 6-month primary endpoint, will be analyzed, and the follow-up will continue under open-label conditions up to month 24.

• Study Type: Interventional
• Enrollment (Actual): 289
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Arlon, Belgium
    • Clinique du Sud Luxembourg - Vivialia-Arlon
  • Jette, Belgium
    • Universitair Ziekenhuis Brussel (UZB)
  • Sint-Niklaas, Belgium
    • General Hospital AZ Nikolaas
• Georgia
  • Tbilisi, Georgia, 48102
    • Aleksandre Aladashvili Clinic LLC
  • Tbilisi, Georgia, 48159
    • National Center for Diabetes Research LTD
  • Tbilisi, Georgia, 48159
    • National Institute of Endocrinology LTD
  • Tbilisi, Georgia, 48159
    • Tbilisi Heart and Vascular Clinic LTD
• Germany
  • Freiburg im Breisgau, Germany
    • Medical Center - University Of Freiburg
  • Glessen, Germany, 35392
    • Universitaetsklinikum Gessen und Marburg GmbH - Medizinische Klinik und Poliklinik III
  • Heidelberg, Germany
    • Diabestesinstitut Heidelberg
  • Ludwigshafen am Rhein, Germany
    • Die Praxis am Ludwigsplatz
  • Münster, Germany
    • Institut fuer Diabetes forschung in Muenster (IDFM)
  • Münster, Germany
    • Schwerpunktpraxis fuer Diabetes & Ernaehrungsmedizin
• Israel
  • Beersheba, Israel
    • Soroka Medical Center
  • Petah Tikva, Israel, 4920235
    • Schneider Children's Medical Center, Petah Tikva
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
• Italy
  • Ancona, Italy, 60123
    • Ospedale Pediatrico G. Salesi - Centro Regionale di Diabetologia Clinica Pediatrica
  • Bari, Italy, 70124
    • Azienda Ospedaliero-Universitaria Conzorziale Policlinico di Bari
  • Catanzaro, Italy
    • Università degli Studi Magna Graecia di Catanzaro, Azienda Ospedaliero-Universitaria Mater Domini
  • Milan, Italy, 20157
    • Universitá degli Studi di Milano - Ospedale Luigi Saco
  • Naples, Italy
    • Centro regionale di Diabetologia Pediatrica "G. Stoppoloni", Azienda Ospedaliera Universitaria "Luigi Vanvitelli"
  • Palermo, Italy, 90127
    • Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"
  • Roma, Italy, 00128
    • Università Campus Bio-Medico di Roma (UCBM) - Policlinico Universitario
  • Roma, Italy
    • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Pediatrico Bambino Gesu
  • Roma, Italy
    • Universita Cattolica del Sacro Cuore - Policlinico Universitario "Agostino Gemelli"
  • Rome, Italy, 00161
    • "Sapienza" Università di Roma- Azienda Ospedaliero Universitaria Policlinico Umberto I
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia, Clinic for Endocrinology, Diabetes and Metabolic Diseases
  • Belgrade, Serbia
    • University Children's Hospital
  • Kragujevac, Serbia, 34000
    • Clinical center Kragujevac, Clinic for internal diseases, Center for endocrinology, diabetes and metabolic diseases
  • Niš, Serbia, 18000
    • Clinical Center Nis, Clinic for endocrinology
  • Niš, Serbia
    • Clinical Center Nis, Clinic for endocrinology
• Slovenia
  • Ljubljana, Slovenia
    • University Children's Hospital, University Medical Center Ljubljana
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham (UAB) - The Kirklin Clinic (TKC) - Multidisciplinary Comprehensive Diabetes Clinic (MCDC)
  • Arizona
    • Phoenix, Arizona, United States, 85021
      • Phoenician Centers for Research and Innovation
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • Sacramento, California, United States, 95821-2123
      • Center of Excellence in Diabetes & Endocrinology (CEDE)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medicine - Barbara Davis Center for Childhood Diabetes (BDC) - Specialty Clinic
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Endocrinology Specialists
  • Florida
    • Hudson, Florida, United States, 34667-7151
      • Diabetes Care Center - Hudson
    • Miami, Florida, United States, 33155
      • Global Life Research Network
    • Orlando, Florida, United States, 32804
      • AdventHealth (Florida Hospital) - Diabetes Institute - Orlando
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associates (ADA)
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
    • Springfield, Illinois, United States, 62711
      • Prairie Education and Research Cooperative d/b/a Central Illinois Diabetes and Clinical
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University - Riley Hospital for Children
  • Kansas
    • Topeka, Kansas, United States, 66606-28
      • The Cotton-O'Neil Diabetes and Endocrinology Center
  • Kentucky
    • Louisville, Kentucky, United States, 40292
      • University of Louisville
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center, Harvard Medical School
  • New York
    • Buffalo, New York, United States, 14203
      • UBMD Physicians Group - Pediatrics - Conventus
  • North Carolina
    • Raleigh, North Carolina, United States, 27610
      • "WakeMed Physician Practices - Pediatric Endocrinology - WakeMed Raleigh Medical Park Location"
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Perelman School of Medicine
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh - UPMC
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Endocrinology and Diabetes Program
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Eastern Virginia Medical School (EVMS) - Strelitz Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 41 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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;
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, sulphonylurea 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ladarixin; 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Drug: Ladarixin; Oral ladarixin twice a day for 13 cycles; Other Names: allosteric inhibitor of CXCL8 (IL-8), CXCR1 and CXCR2 receptors
Placebo Comparator: Placebo; matching placebo b.i.d. for 13 cycles of 14 days on/14 days off	Drug: Placebo; Oral placebo twice a day for 13 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 2-hour Area Under the Concentration-time Curve (AUC) of C-peptide Response to the Mixed Model Tolerance Test (MMTT)	Change from baseline in the 2-hour C-peptide Area Under the Curve (AUC) following a Mixed-Meal Tolerance Test (MMTT) at Month 6. The analysis used an adjusted ANCOVA model with the change from baseline in log(AUC + 1) as the dependent variable. Qualitative independent variables included treatment group, age group, sex, and BMI group, with the baseline value as a quantitative covariate. Missing data at Month 6 were handled via multiple imputation using a retrieved dropout approach. Missing values were imputed using a regression model based on the participant's allocated treatment arm and baseline value, utilizing data from participants who discontinued treatment but completed the Month 6 measurement. Baseline is defined as the last visit prior to randomization. Change from Baseline is defined as post-baseline visit value minus baseline visit value. The adjusted mean along with its the corresponding 95% confidence interval (CI) has been presented.	Baseline and at Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 2-hour AUC of C-peptide Response to the MMTT at Months 12, 18, and 24	Change from baseline in the 2-hour C-peptide AUC following a MMTT at Months 6, 12, and 18. The analysis used an adjusted ANCOVA model with the change from baseline in log(AUC + 1) as the dependent variable. Qualitative independent variables included treatment group, age group, sex, and BMI group, with the baseline value as a quantitative covariate. Missing data at Months 12, 18 and 24 were handled via multiple imputation using a retrieved dropout approach. Missing values were imputed using a regression model based on the participant's allocated treatment arm and baseline value, utilizing data from participants who discontinued treatment but completed the measurement at the timepoint of interest. Intermediate timepoints were included as covariates in the model. Baseline is defined as the last visit prior to randomization. Change from Baseline is defined as post-baseline visit value minus baseline visit value.	Baseline and at Months 12, 18, and 24
Change in Glycated Hemoglobin (HbA1c) From Baseline	The change from baseline in HbA1c was analyzed using an adjusted ANCOVA model. The dependent variable is the change from baseline in HbA1c at each respective time point, with treatment, age group, sex, and BMI group as qualitative independent variables and the baseline value as a quantitative covariate. . Missing data are addressed via Multiple Imputation (MI) using a retrieved dropout approach, where values are imputed based on a regression model incorporating treatment arm, baseline value, and intermediate assessments as covariates. Baseline is defined as the last visit prior to randomization. Change from Baseline is defined as post-baseline visit value minus baseline visit value. The adjusted mean along with its the corresponding 95% confidence interval (CI) has been presented.	Baseline and at Months 6, 12, 18 and 24
Percentage of Participants With HbA1c <7% Who Did Not Experience Severe Hypoglycemic Events During Treatment	The proportion of participants with HbA1c < 7% was calculated by timepoint: the numerator was the number of participants with events occurring at a specific timepoint (month X visit), without cumulating participants with events up to that timepoint. Participants with severe hypoglycemic events were considered cumulatively and only events up to month 12 were considered (condition was evaluated by considering treatment period only). If HbA1c ≥ 7% or the participant had experienced a severe hypoglycemic event, then the endpoint was equal to "No" even in the case of one missing component. If either the HbA1c or severe hypoglycemic event data was missing, but the other satisfied the criteria for the endpoint, then the response to the endpoint was missing.	At Months 6, 12, 18, and 24
Average (Previous 3 Days) Daily Insulin Requirement International Units Per Kilogram Per Day (IU/kg/Day)	The average daily insulin requirement at each visit was calculated from the daily insulin requirement measured at the 3 days prior to the visit.	At Months 6, 12, 18, and 24
Percentage of Participants With HbA1c <7% and Daily Insulin Requirement <0.5 IU/kg/Day	Percentage of participants with HbA1c <7% and daily insulin requirement <0.5 (IU/Kg/day) was calculated for each time point, the numerator is the number of participants in each treatment group with events occurring at a specific timepoint, and the denominator is the number of participants in each treatment group reaching the specific visit.	At Months 6, 12, 18, and 24
Number of Self-reported Episodes of Severe Hypoglycemia	This outcome assessed the total number of self-reported episodes of severe hypoglycemia occurring across all participants.	Post-baseline up to Month 24
Percentage of Patients Not Requiring Insulin Therapy	This outcome assessed the percentage of participants who did not require an insulin therapy at the timepoint of interest.	Months 6, 12, 18 and 24
Estimated Glucose Disposal Rate (eGDR)	Estimated Glucose Disposal Rate (eGDR) is a marker for the Assessment of Insulin Resistance and a validated clinical tool for estimating insulin sensitivity in type 1 diabetes. The eGDR was calculated using a formula incorporating Glycated Hemoglobin (HbA1c), hypertension status (blood pressure), and the Waist-to-Hip Ratio (WHR), with results expressed in milligrams per kilogram per minute (mg/kg/min).	Months 6, 12, 18, and 24

Collaborators and Investigators

• Sponsor: Dompé Farmaceutici S.p.A
• Investigators: Study Director: Enrico Minnella, MD, Dompé Farmaceutici

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2021
• Primary Completion (Actual): March 31, 2025
• Study Completion (Actual): October 21, 2025

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 9, 2020
• First Posted (Actual): November 13, 2020

Study Record Updates

• Last Update Posted (Actual): August 31, 2026
• Last Update Submitted That Met QC Criteria: August 26, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: type1 diabetes
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Intercellular Signaling Peptides and Proteins; Cytokines; Inflammation Mediators; Interleukins; Receptors, Cytokine; Receptors, Immunologic; Receptors, Interleukin-8; Receptors, CXCR; Receptors, Chemokine; Receptors, Interleukin; Chemokines, CXC; Chemokines; Chemotactic Factors; Receptors, Interleukin-8B; Interleukin-8; 2'-((4'-trifluoromethanesulfonyloxy)phenyl)-N-methanesulfonylpropionamide
• Other Study ID Numbers: LDX0319; 2020-001926-71 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No