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

NCT ID: NCT04899271

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-14
• Study Completion Date: 2023-10-11

Brief 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.

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.

Conditions

New-onset Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ladarixin

The treatment group received 400 mg b.i.d. for 13 cycles of 14 days on/14 days off)

Group Type: EXPERIMENTAL

Ladarixin

Intervention Type: DRUG

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

Placebo

The control group received matched placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Interventions

Ladarixin

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

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Other Intervention Names

LDX

Eligibility Criteria

Inclusion Criteria

1. Male and female patients aged 18-45 years, inclusive;

2. New-onset T1D (1st IMP dose within 100 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 multiple daily injections (MDI) or Continuous Subcutaneous Insulin Infusion (CSII);

5. Fasting C peptide ≥0.205nmol/L on two occasions;

6. Patient able to comply with all protocol procedures for the duration of the study, including scheduled follow-up visits and examinations;

7. Patients who have given written informed consent prior of any study-related procedure not part of standard medical care.

Exclusion Criteria

1. 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;

2. 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);

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. A history of significant cardiovascular disease/abnormality

7. Occurrence of an episode of ketoacidosis or hypoglycemic coma in the past 2 weeks;

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, sulphanylurea hypoglycemics (e.g. tolbutamide, glipizide, glibenclamide/glyburide, glimepiride, nateglinide) and high dose of amitriptyline (>50 mg/day)];

10. 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.);

11. 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;

12. 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);

13. 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;

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dompé Farmaceutici S.p.A

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Enrico M Minnella, MD

Role: STUDY_DIRECTOR

Dompé Farmaceutici

Locations

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

Aurora, Colorado, United States

Atlanta Diabetes Associates (ADA)

Atlanta, Georgia, United States

Universitair Ziekenhuis Brussel (UZB)

Jette, , Belgium

National Center for Diabetes Research LTD

Tbilisi, , Georgia

National Institute of Endocrinology LTD

Tbilisi, , Georgia

Universitaetsklinikum Gessen und Marburg GmbH - Medizinische Klinik und Poliklinik III

Glessen, , Germany

St. Josefskrankenhaus Diabestesinstitut Heidelberg

Heidelberg, , Germany

Institut fuer Diabetes forschung in Muenster (IDFM)

Münster, , Germany

Azienda Ospedaliero-Universitaria Conzorziale Policlinico di Bari

Bari, , Italy

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

Catanzaro, , Italy

Universitá degli Studi di Milano - Ospedale Luigi Sacco

Milan, , Italy

Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"

Palermo, , Italy

Università Campus Bio-Medico di Roma (UCBM)

Roma, , Italy

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

Rome, , Italy

University of Serbia, Clinic for Endocrinology, Diabetes and Metabolic Diseases

Belgrade, , Serbia

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

Kragujevac, , Serbia

Countries

United States; Belgium; Georgia; Germany; Italy; Serbia

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-002966-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LDX0419

Identifier Type: -

Identifier Source: org_study_id