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New-onset Type 1 DiabetesPhase 2NCT04899271

A Study to Assess Efficacy/Safety of Ladarixin in Type 1 Diabetes Patients With Preserved ß-cell Function at Baseline.

A Phase 2 study testing Ladarixin in people with New-onset Type 1 Diabetes, run by Dompé Farmaceutici S.p.A at 16 sites in 6 countries.

Terminated

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

Official record
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Trial summary

The objective of this clinical trial was to assess whether ladarixin treatment is effective to improve glycemic control in newly diagnosed Type 1 Diabetes (T1D) adult patients with preserved β-cell function. The safety of ladarixin in the specific clinical setting was also evaluated. Read more about this study

Who is it for?
Ages 18 to 45 years
Conditions the study is for
New-onset Type 1 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
25 participants
Where
16 sitesin 6 countries
Study dates
14 Dec 2020to 11 Oct 2023
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 18 to 45 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Male and female patients aged 18-45 years, inclusive;
  • New-onset T1D (1st IMP dose within 100 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 multiple daily injections (MDI) or Continuous Subcutaneous Insulin Infusion (CSII);
  • Fasting C peptide ≥0.205nmol/L on two occasions;
  • 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.

Who cannot join

  • 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;
  • Moderate to severe renal impairment as per estimated Glomerular Filtration Rate (eGFR) 60 mL/min/1.73 m2, as determined using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation (see Appendix 14.4.3);
  • 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];
  • Hypoalbuminemia defined as serum albumin < 3 g/dL;
  • QTcF > 470 msec;
  • A history of significant cardiovascular disease/abnormality
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  • Occurrence of an episode of ketoacidosis or hypoglycemic coma in the past 2 weeks;
  • 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)];
  • Previous (within 2 weeks prior to randomization) 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 (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;
  • Significant systemic infection during the 4 weeks before the first 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);
  • Hepatitis A (IgM), hepatitis B (not due to immunization), hepatitis C and HIV positive serologic status Serologic evidence of current infectious liver disease (hepatitis A, B, or C), including anti hepatitis A virus (immunoglobulin M), hepatitis B surface antigen, or anti hepatitis C virus 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).

Trial locations and contacts

16 sites in 6 countries.

16 sites in 6 countries

Italy6 sites
  • Azienda Ospedaliero-Universitaria Conzorziale Policlinico di Bari

    Bari, 70124

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

    Catanzaro, 88100

  • Universitá degli Studi di Milano - Ospedale Luigi Sacco

    Milan, 20157

  • Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"

    Palermo, 90127

  • Università Campus Bio-Medico di Roma (UCBM)

    Roma, 00128

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

    Rome, 00161

Other trials in Italy

Germany3 sites
  • Universitaetsklinikum Gessen und Marburg GmbH - Medizinische Klinik und Poliklinik III

    Glessen, 35392

  • St. Josefskrankenhaus Diabestesinstitut Heidelberg

    Heidelberg, 69115

  • Institut fuer Diabetes forschung in Muenster (IDFM)

    Münster, 48145

Other trials in Germany

United States2 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

Other trials in United States

Georgia2 sites
  • National Center for Diabetes Research LTD

    Tbilisi, 48159

  • National Institute of Endocrinology LTD

    Tbilisi, 48159

Other trials in Georgia

Serbia2 sites
  • University of Serbia, Clinic for Endocrinology, Diabetes and Metabolic Diseases

    Belgrade, 11000

  • University of Kragujevac, Clinic for internal diseases, Center for endocrinology, diabetes and metabolic diseases

    Kragujevac, 34000

Other trials in Serbia

Belgium1 site
  • Universitair Ziekenhuis Brussel (UZB)

    Jette

Other trials in Belgium

About this study

Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of 400 mg Twice a Day Oral Ladarixin in Patients With New-onset Type 1 Diabetes and Preserved Beta-cell Function at Baseline.

The objective of this clinical trial was to assess whether ladarixin treatment is effective to improve glycemic control in newly diagnosed Type 1 Diabetes (T1D) adult patients with preserved β-cell function.

The safety of ladarixin in the specific clinical setting was also evaluated.

Read the detailed description

This was a phase II clinical trial designed as a randomized, double-blind, placebo-controlled, multicenter study to evaluate whether ladarixin is effective in preserving β-cell function and slowing-down the progression of T1D in adult patients with new-onset T1D and preserved β- cell function (fasting C-peptide ≥0.205 nmol/L) at baseline.

Seventy-five (75) patients were to be randomized based on an unbalanced randomization allocation ratio (2:1) to ladarixin hard gelatine capsules for oral administration (2 x 200 mg two times a day [b.i.d.] for 13 cycles of 14 days on/14 days off) or matched placebo. Assuming a 10% drop-out rate, approximately 84 patients were expected to be enrolled and to be treated for 1 year.

Each patient was to be involved in the study for a run-in period (screening and baseline assessments) followed by a randomization visit, a treatment period of 12 months, and a post-randomization period up to 18 months from the 1st treatment dose.

The study enrolment was stopped, though, on 28 March 2022, due to low enrolment rate, at the randomization of the 25th patient. The study terminated early, on 11 October 2023 (LPLV).

Due to the early termination of the study, efficacy analyses were reduced in scope given the limited sample size of the study compared with the one expected.

Being tested
Ladarixin, Placebo
Keywords
Type 1 diabetes
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

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

  • LadarixinDrug

    Also called LDX

    400 mg b.i.d. for 13 cycles of 14 days on/14 days off

  • PlaceboOther

    Placebo was administered orally with the same scheme of administration of LDX to preserve blinding

Study groups in NCT04899271
Study groupRoleWhat they receive
LadarixinExperimentalThe treatment group received 400 mg b.i.d. for 13 cycles of 14 days on/14 days off)
Receives: Drug: Ladarixin
PlaceboPlacebo comparatorThe control group received matched placebo
Receives: Other: Placebo

What is being measured

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

  1. Number of Patients With HbA1c <7% and Daily Insulin Requirement <0.50 IU/Kg/Day at Month 12

    The sample size of the study is calculated on the "proportion of patients with a HbA1c < 7% and daily insulin requirement <0.50 IU/Kg/day", a post-hoc composite endpoint derived from data of the phase 2 trial (MEX0114), considering a larger effect size expected from the longer treatment length (one year versus 3 months).

    The time frame for the primary endpoint has been set at Month 12 (Week 52) in order to evaluate the potential of ladarixin effects on a long-term projection.

    Please note that "proportion" is expressed as "count" (number + % of participants)

    Measured: Month 12 (52±2 weeks)

Secondary outcomes (10)
  1. Number of Patients With HbA1c < 7% and Daily Insulin Requirement <0.50 IU/Kg/Day at Months 6 and 18

    The sample size of the study is calculated on the "proportion of patients with a HbA1c < 7% and daily insulin requirement <0.50 IU/Kg/day", a post-hoc composite endpoint derived from data of the phase 2 trial (MEX0114), considering a larger effect size expected from the longer treatment length (one year versus 3 months). Follow-up is extended up to 18 months to evaluate the potential persistency of any glycemic benefit. Please note that "proportion" is expressed as "count" (number + % of participants)

    Measured: Month 6 (26±2 weeks) and Month 18 (78±2 weeks)

  2. Number of Patients With a Reduction in HbA1c% > 0.5% From Baseline and Daily Insulin Requirement <0.50 IU/Kg/Day at Months 6, 12 and 18

    The number of patients with a reduction in HbA1c% > 0.5% from baseline and daily insulin requirement <0.50 IU/Kg/day was calculated at the hereunder specified timepoints.

    Measured: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks )

  3. Change From Baseline in 2-hour AUC of C-peptide Response to the MMTT at Months 6, 12 and 18

    C-peptide level is a widely used measure of pancreatic beta-cell function and the MMTT is one of the methods for its estimation. AUC stands for Area Under the Curve.

    AUC calculation was based on actual rather scheduled timings and it was calculated using the trapezoidal rule. C-peptide 0-120 min AUC (nmol/L) values were calculated based on all Basal-120min C-peptide values. Unscheduled assessments were excluded from the analysis.

    Measured: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks)

  4. Changes From Baseline in Percentage Glycated Hemoglobin (HbA1c) Levels at Months 6, 12 and 18

    HbA1c measurement can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement.

    An HbA1c of 6.5% is recommended as the cut point for diagnosing diabetes. A value of less than 6.5% does not exclude diabetes diagnosed using glucose tests. An A1C test measures the percentage of red blood cells that have glucose-coated hemoglobin.

    Measured: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks)

  5. Number of Patients With HbA1c < 7% Who Did Not Experience Severe Hypoglycemic Events During Treatment at Months 6,12 and 18

    For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.

    Measured: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks)

  6. Overall Number of Self-reported Episodes of Severe Hypoglycemia

    For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration. Data reported refer to the overall number of episodes recorded by all analyzed patients in the two arms/groups (Ladarixin and placebo).

    Measured: From baseline to study termination (month 18, week 78)

  7. Blood Glucose Levels for Patients Reporting Severe Hypoglycemia at Months 6, 12 and 18

    A severe hypoglycemic event was defined as an event with 1 of the following symptoms: "memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54mg/dL or prompt recovery after oral carbohydrate, i.e. glucose, or glucagon administration. Summary statistics of blood glucose level (mg/dL) are provided by treatment group at each time point for patients reporting severe hypoglycemia.

    Measured: Months 6 (week 26±2), 12 (week 52±2) and 18 (week 78±2)

  8. Change From Baseline in Average (Previous 3 Days) Daily Insulin Requirements (IU/kg/Day) at Months 6,12 and 18

    For the purpose of this study, daily insulin is averaged over the previous 3 days.Insulin requirement (IU/kg/day averaged over the previous 3 days) was to be recorded to Months 6, 12 and 18.

    Patients were admitted to intensive diabetes management, according to current ADA recommendation [2014]. Patients were instructed to self-monitor their glucose values at least 4 times a day and to report (glucose meter/log) outcome to the diabetes management team. Insulin intake was adjusted to target HbA1c levels of less than 7% and self-monitored (fingerstick):

    • pre-prandial blood glucose of 70-130 mg/dL
    • post-prandial blood glucose < 180 mg/dL
    • bed-time blood glucose of 110-150 mg/dL

    Measured: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks)

  9. Change From Baseline in Estimated Glucose Disposal Rate (eGDR) at Months 6, 12 and 18

    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.

    Measured: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks)

  10. Number of Patients With at Least One Adverse Events (AEs), Serious or Not Serious

    An AE is any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the trial intervention.

    A serious adverse event is an adverse event that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect.

    Measured: Throughout the study up to 18 months

Timeline

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

  1. First posted24 May 2021
  2. Study start14 Dec 2020
  3. Primary completion27 Apr 2023
  4. Study completion11 Oct 2023

Why it stopped: low recruitment rate

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
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04899271
Sponsor's protocol ID
LDX0419
Other IDs
2020-002966-15
Status last verified
May 2025
First submitted
10 May 2021
Last updated
14 May 2025
Data monitoring committee
No
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 New-onset Type 1 Diabetes, run by Dompé Farmaceutici S.p.A at 16 sites in 6 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 7 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 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Italy, Germany, United States, Georgia, Serbia and 1 more country. 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 14 May 2025). 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?

Number of Patients With HbA1c <7% and Daily Insulin Requirement <0.50 IU/Kg/Day at Month 12 (time frame: Month 12 (52±2 weeks)). 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 14 May 2025.

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