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

NCT ID: NCT04628481

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

141 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-12

Study Completion Date

2025-10-21

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Recent Onset type1 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The study proceeded under double-blind condition up to month 18 visit of the last patient randomized. Thereafter, the blind was broken and remaining follow-up will proceeded in an open fashion. This approach allowed to anticipate access to efficacy data without significantly affecting data integrity.

Study Groups

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Ladarixin

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

Group Type EXPERIMENTAL

Ladarixin

Intervention Type DRUG

Oral ladarixin twice a day for 13 cycles

Placebo

matching placebo b.i.d. for 13 cycles of 14 days on/14 days off

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Oral placebo twice a day for 13 cycles

Interventions

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Ladarixin

Oral ladarixin twice a day for 13 cycles

Intervention Type DRUG

Placebo

Oral placebo twice a day for 13 cycles

Intervention Type DRUG

Other Intervention Names

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

Eligibility Criteria

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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.
Minimum Eligible Age

14 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dompé Farmaceutici S.p.A

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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

Birmingham, Alabama, United States

Site Status

Phoenician Centers for Research and Innovation

Phoenix, Arizona, United States

Site Status

University of California San Diego

La Jolla, California, United States

Site Status

Center of Excellence in Diabetes & Endocrinology (CEDE)

Sacramento, California, United States

Site Status

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

Aurora, Colorado, United States

Site Status

Christiana Care Endocrinology Specialists

Newark, Delaware, United States

Site Status

Diabetes Care Center - Hudson

Hudson, Florida, United States

Site Status

Global Life Research Network

Miami, Florida, United States

Site Status

AdventHealth (Florida Hospital) - Diabetes Institute - Orlando

Orlando, Florida, United States

Site Status

Atlanta Diabetes Associates (ADA)

Atlanta, Georgia, United States

Site Status

The University of Chicago

Chicago, Illinois, United States

Site Status

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

Springfield, Illinois, United States

Site Status

Indiana University - Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

The Cotton-O'Neil Diabetes and Endocrinology Center

Topeka, Kansas, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Joslin Diabetes Center, Harvard Medical School

Boston, Massachusetts, United States

Site Status

UBMD Physicians Group - Pediatrics - Conventus

Buffalo, New York, United States

Site Status

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

Raleigh, North Carolina, United States

Site Status

University of Pennsylvania Perelman School of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh - UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Cook Children's Endocrinology and Diabetes Program

Fort Worth, Texas, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

Eastern Virginia Medical School (EVMS) - Strelitz Diabetes Center

Norfolk, Virginia, United States

Site Status

Clinique du Sud Luxembourg - Vivialia-Arlon

Arlon, , Belgium

Site Status

Universitair Ziekenhuis Brussel (UZB)

Jette, , Belgium

Site Status

General Hospital AZ Nikolaas

Sint-Niklaas, , Belgium

Site Status

Aleksandre Aladashvili Clinic LLC

Tbilisi, , Georgia

Site Status

National Center for Diabetes Research LTD

Tbilisi, , Georgia

Site Status

National Institute of Endocrinology LTD

Tbilisi, , Georgia

Site Status

Tbilisi Heart and Vascular Clinic LTD

Tbilisi, , Georgia

Site Status

Medical Center - University of Freiburg

Freiburg im Breisgau, , Germany

Site Status

Universitaetsklinikum Gessen und Marburg GmbH - Medizinische Klinik und Poliklinik III

Glessen, , Germany

Site Status

Diabestesinstitut Heidelberg

Heidelberg, , Germany

Site Status

Die Praxis am Ludwigsplatz

Ludwigshafen am Rhein, , Germany

Site Status

Institut fuer Diabetes forschung in Muenster (IDFM)

Münster, , Germany

Site Status

Schwerpunktpraxis fuer Diabetes & Ernaehrungsmedizin

Münster, , Germany

Site Status

Soroka Medical Center

Beersheba, , Israel

Site Status

Schneider Children's Medical Center, Petah Tikva

Petah Tikva, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

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

Ancona, , Italy

Site Status

Azienda Ospedaliero-Universitaria Conzorziale Policlinico di Bari

Bari, , Italy

Site Status

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

Catanzaro, , Italy

Site Status

Universitá degli Studi di Milano - Ospedale Luigi Saco

Milan, , Italy

Site Status

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

Napoli, , Italy

Site Status

Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"

Palermo, , Italy

Site Status

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

Roma, , Italy

Site Status

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

Roma, , Italy

Site Status

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

Roma, , Italy

Site Status

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

Rome, , Italy

Site Status

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

Belgrade, , Serbia

Site Status

University Children's Hospital

Belgrade, , Serbia

Site Status

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

Kragujevac, , Serbia

Site Status

Clinical Center Nis, Clinic for endocrinology

Niš, , Serbia

Site Status

Clinical Center Nis, Clinic for endocrinology

Niš, , Serbia

Site Status

University Children's Hospital, University Medical Center Ljubljana

Ljubljana, , Slovenia

Site Status

Countries

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United States Belgium Georgia Germany Israel Italy Serbia Slovenia

Other Identifiers

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2020-001926-71

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LDX0319

Identifier Type: -

Identifier Source: org_study_id