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Recent Onset type1 DiabetesPhase 2NCT04628481

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

A Phase 2 study testing Ladarixin in people with Recent Onset type1 Diabetes, run by Dompé Farmaceutici S.p.A at 57 sites in 8 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 14 to 45 years
Conditions the study is for
Recent Onset type1 Diabetes
What is being tested?
Ladarixin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
289 participants
Where
57 sitesin 8 countries
Study dates
12 Jan 2021to 21 Oct 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 14 to 45 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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 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;
  • 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.

Who cannot join

  • A type 2 diabetes diagnosis or any other unstable chronic disease for which dose adjustment of specific medication is anticipated during the trial;
  • 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;
Show all 14Show fewer
  • 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, sulphonylurea hypoglycemics (e.g. tolbutamide, glipizide, glibenclamide/glyburide, glimepiride, nateglinide) and high dose amitriptyline (> 50 mg/day)];
  • 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.);
  • 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 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);
  • 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 spermicide foam); abstinence.

Trial locations and contacts

57 sites in 8 countries.

57 sites in 8 countries

United States25 sites
  • Atlanta Diabetes Associates (ADA)

    Atlanta, Georgia, 30318

  • University of Colorado School of Medicine - Barbara Davis Center for Childhood Diabetes (BDC) - Specialty Clinic

    Aurora, Colorado, 80045

  • University of Alabama at Birmingham (UAB) - The Kirklin Clinic (TKC) - Multidisciplinary Comprehensive Diabetes Clinic (MCDC)

    Birmingham, Alabama, 35294

  • Joslin Diabetes Center, Harvard Medical School

    Boston, Massachusetts, 02215

  • UBMD Physicians Group - Pediatrics - Conventus

    Buffalo, New York, 14203

  • The University of Chicago

    Chicago, Illinois, 60637

  • Cook Children's Endocrinology and Diabetes Program

    Fort Worth, Texas, 76104

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Diabetes Care Center - Hudson

    Hudson, Florida, 34667-7151

  • Indiana University - Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of California San Diego

    La Jolla, California, 92093

  • University of Louisville

    Louisville, Kentucky, 40292

  • Global Life Research Network

    Miami, Florida, 33155

  • Christiana Care Endocrinology Specialists

    Newark, Delaware, 19713

  • Eastern Virginia Medical School (EVMS) - Strelitz Diabetes Center

    Norfolk, Virginia, 23510

  • AdventHealth (Florida Hospital) - Diabetes Institute - Orlando

    Orlando, Florida, 32804

  • University of Pennsylvania Perelman School of Medicine

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Phoenician Centers for Research and Innovation

    Phoenix, Arizona, 85021

  • UPMC Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15224

  • University of Pittsburgh - UPMC

    Pittsburgh, Pennsylvania, 15261

  • "WakeMed Physician Practices - Pediatric Endocrinology - WakeMed Raleigh Medical Park Location"

    Raleigh, North Carolina, 27610

  • Center of Excellence in Diabetes & Endocrinology (CEDE)

    Sacramento, California, 95821-2123

  • Prairie Education and Research Cooperative d/b/a Central Illinois Diabetes and Clinical

    Springfield, Illinois, 62711

  • The Cotton-O'Neil Diabetes and Endocrinology Center

    Topeka, Kansas, 66606-28

Other trials in United States

Italy10 sites
  • Ospedale Pediatrico G. Salesi - Centro Regionale di Diabetologia Clinica Pediatrica

    Ancona, 60123

  • Azienda Ospedaliero-Universitaria Conzorziale Policlinico di Bari

    Bari, 70124

  • Università degli Studi Magna Graecia di Catanzaro, Azienda Ospedaliero-Universitaria Mater Domini

    Catanzaro

  • Universitá degli Studi di Milano - Ospedale Luigi Saco

    Milan, 20157

  • Centro regionale di Diabetologia Pediatrica "G. Stoppoloni", Azienda Ospedaliera Universitaria "Luigi Vanvitelli"

    Naples

  • Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"

    Palermo, 90127

  • Università Campus Bio-Medico di Roma (UCBM) - Policlinico Universitario

    Roma, 00128

  • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Pediatrico Bambino Gesu

    Roma

  • Universita Cattolica del Sacro Cuore - Policlinico Universitario "Agostino Gemelli"

    Roma

  • "Sapienza" Università di Roma- Azienda Ospedaliero Universitaria Policlinico Umberto I

    Rome, 00161

Other trials in Italy

Germany6 sites
  • Medical Center - University of Freiburg

    Freiburg im Breisgau

  • Universitaetsklinikum Gessen und Marburg GmbH - Medizinische Klinik und Poliklinik III

    Glessen, 35392

  • Diabestesinstitut Heidelberg

    Heidelberg

  • Die Praxis am Ludwigsplatz

    Ludwigshafen am Rhein

  • Institut fuer Diabetes forschung in Muenster (IDFM)

    Münster

  • Schwerpunktpraxis fuer Diabetes & Ernaehrungsmedizin

    Münster

Other trials in Germany

Serbia5 sites
  • Clinical Center of Serbia, Clinic for Endocrinology, Diabetes and Metabolic Diseases

    Belgrade, 11000

  • University Children's Hospital

    Belgrade

  • Clinical center Kragujevac, Clinic for internal diseases, Center for endocrinology, diabetes and metabolic diseases

    Kragujevac, 34000

  • Clinical Center Nis, Clinic for endocrinology

    Niš, 18000

  • Clinical Center Nis, Clinic for endocrinology

    Niš

Other trials in Serbia

Georgia4 sites
  • Aleksandre Aladashvili Clinic LLC

    Tbilisi, 48102

  • National Center for Diabetes Research LTD

    Tbilisi, 48159

  • National Institute of Endocrinology LTD

    Tbilisi, 48159

  • Tbilisi Heart and Vascular Clinic LTD

    Tbilisi, 48159

Other trials in Georgia

Belgium3 sites
  • Clinique du Sud Luxembourg - Vivialia-Arlon

    Arlon

  • Universitair Ziekenhuis Brussel (UZB)

    Jette

  • General Hospital AZ Nikolaas

    Sint-Niklaas

Other trials in Belgium

Israel3 sites
  • Soroka Medical Center

    Beersheba

  • Schneider Children's Medical Center, Petah Tikva

    Petah Tikva, 4920235

  • Tel Aviv Sourasky Medical Center

    Tel Aviv

Other trials in Israel

Slovenia1 site
  • University Children's Hospital, University Medical Center Ljubljana

    Ljubljana

Other trials in Slovenia

About this study

Official title: 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.

Read the 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.

Being tested
Ladarixin, Placebo
Keywords
type1 diabetes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LadarixinDrug

    Also called allosteric inhibitor of CXCL8 (IL-8), CXCR1 and CXCR2 receptors

    Oral ladarixin twice a day for 13 cycles

  • PlaceboDrug

    Oral placebo twice a day for 13 cycles

Study groups in NCT04628481
Study groupRoleWhat they receive
LadarixinExperimental400 mg b.i.d. for 13 cycles of 14 days on/14 days off
Receives: Drug: Ladarixin
PlaceboPlacebo comparatormatching placebo b.i.d. for 13 cycles of 14 days on/14 days off
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline and at Month 6

Secondary outcomes (8)
  1. 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.

    Measured: Baseline and at Months 12, 18, and 24

  2. 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.

    Measured: Baseline and at Months 6, 12, 18 and 24

  3. 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.

    Measured: At Months 6, 12, 18, and 24

  4. 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.

    Measured: At Months 6, 12, 18, and 24

  5. 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.

    Measured: At Months 6, 12, 18, and 24

  6. 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.

    Measured: Post-baseline up to Month 24

  7. 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.

    Measured: Months 6, 12, 18 and 24

  8. 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).

    Measured: Months 6, 12, 18, and 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2020
  2. Study start12 Jan 2021
  3. Primary completion31 Mar 2025
  4. Study completion21 Oct 2025

Why it stopped: The study was stopped due to futility as per protocol

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Patients were 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 were balanced within centers.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
289 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04628481
Sponsor's protocol ID
LDX0319
Other IDs
2020-001926-71
Status last verified
Aug 2026
First submitted
9 Nov 2020
Last updated
31 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ladarixin in people with Recent Onset type1 Diabetes, run by Dompé Farmaceutici S.p.A at 57 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 57 sites in United States, Italy, Germany, Serbia, Georgia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in 2-hour Area Under the Concentration-time Curve (AUC) of C-peptide Response to the Mixed Model Tolerance Test (MMTT) (time frame: Baseline and at Month 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.

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