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

NCT04628481 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: LDX03192020-001926-71
• Study Type: interventional
• Target: 141
• Locations: 8 countries
• Sites: 57

Brief 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.

Conditions

Recent Onset type1 Diabetes

Keywords

type1 diabetes

Outcome Measures

Primary Outcomes (1)

• Change from baseline in 2-hour AUC of C-peptide response to the Mixed Model Tolerance Test (MMTT)

  C-peptide level is an indirect measure of pancreatic beta-cell function. The MMTT was performed after an overnight fast, at baseline

  Month 6

Secondary Outcomes (14)

• Change from baseline in 2-hour AUC of C-peptide response to the MMTT

  Months 12, 18 and 24

• Change in HbA1c from baseline

  Months 6, 12, 18 and 24

• Time in range (TIR) by Continuous Glucose Monitoring (CGM)

  Months 6, 12, 18, 24

• Proportion of patients with HbA1c <7% who did not experience severe hypoglycemic events during treatment

  Months 6, 12, 18, 24

• Average (previous 3 days) daily insulin requirement (IU/kg/day)

  Months 6, 12, 18, 24

Study Arms (2)

Ladarixin

EXPERIMENTAL

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

Drug: Ladarixin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Ladarixin DRUG

Oral ladarixin twice a day for 13 cycles

Also known as: allosteric inhibitor of CXCL8 (IL-8), CXCR1 and CXCR2 receptors

Ladarixin

Placebo DRUG

Oral placebo twice a day for 13 cycles

Placebo

Eligibility Criteria

• Age: 14 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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;
• 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.

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (57)

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

Birmingham, Alabama, 35294, United States

Location

Phoenician Centers for Research and Innovation

Phoenix, Arizona, 85021, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

Center of Excellence in Diabetes & Endocrinology (CEDE)

Sacramento, California, 95821-2123, United States

Location

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

Aurora, Colorado, 80045, United States

Location

Christiana Care Endocrinology Specialists

Newark, Delaware, 19713, United States

Location

Diabetes Care Center - Hudson

Hudson, Florida, 34667-7151, United States

Location

Global Life Research Network

Miami, Florida, 33155, United States

Location

AdventHealth (Florida Hospital) - Diabetes Institute - Orlando

Orlando, Florida, 32804, United States

Location

Atlanta Diabetes Associates (ADA)

Atlanta, Georgia, 30318, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

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

Springfield, Illinois, 62711, United States

Location

Indiana University - Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

The Cotton-O'Neil Diabetes and Endocrinology Center

Topeka, Kansas, 66606-28, United States

Location

University of Louisville

Louisville, Kentucky, 40292, United States

Location

Joslin Diabetes Center, Harvard Medical School

Boston, Massachusetts, 02215, United States

Location

UBMD Physicians Group - Pediatrics - Conventus

Buffalo, New York, 14203, United States

Location

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

Raleigh, North Carolina, 27610, United States

Location

University of Pennsylvania Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Pittsburgh - UPMC

Pittsburgh, Pennsylvania, 15261, United States

Location

Cook Children's Endocrinology and Diabetes Program

Fort Worth, Texas, 76104, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Eastern Virginia Medical School (EVMS) - Strelitz Diabetes Center

Norfolk, Virginia, 23510, United States

Location

Clinique du Sud Luxembourg - Vivialia-Arlon

Arlon, Belgium

Location

Universitair Ziekenhuis Brussel (UZB)

Jette, Belgium

Location

General Hospital AZ Nikolaas

Sint-Niklaas, Belgium

Location

Aleksandre Aladashvili Clinic LLC

Tbilisi, 48102, Georgia

Location

National Center for Diabetes Research LTD

Tbilisi, 48159, Georgia

Location

National Institute of Endocrinology LTD

Tbilisi, 48159, Georgia

Location

Tbilisi Heart and Vascular Clinic LTD

Tbilisi, 48159, Georgia

Location

Medical Center - University of Freiburg

Freiburg im Breisgau, Germany

Location

Universitaetsklinikum Gessen und Marburg GmbH - Medizinische Klinik und Poliklinik III

Glessen, 35392, Germany

Location

Diabestesinstitut Heidelberg

Heidelberg, Germany

Location

Die Praxis am Ludwigsplatz

Ludwigshafen am Rhein, Germany

Location

Institut fuer Diabetes forschung in Muenster (IDFM)

Münster, Germany

Location

Schwerpunktpraxis fuer Diabetes & Ernaehrungsmedizin

Münster, Germany

Location

Soroka Medical Center

Beersheba, Israel

Location

Schneider Children's Medical Center, Petah Tikva

Petah Tikva, 4920235, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

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

Ancona, 60123, Italy

Location

Azienda Ospedaliero-Universitaria Conzorziale Policlinico di Bari

Bari, 70124, Italy

Location

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

Catanzaro, Italy

Location

Universitá degli Studi di Milano - Ospedale Luigi Saco

Milan, 20157, Italy

Location

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

Naples, Italy

Location

Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"

Palermo, 90127, Italy

Location

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

Roma, 00128, Italy

Location

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

Roma, Italy

Location

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

Roma, Italy

Location

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

Rome, 00161, Italy

Location

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

Belgrade, 11000, Serbia

Location

University Children's Hospital

Belgrade, Serbia

Location

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

Kragujevac, 34000, Serbia

Location

Clinical Center Nis, Clinic for endocrinology

Niš, 18000, Serbia

Location

Clinical Center Nis, Clinic for endocrinology

Niš, Serbia

Location

University Children's Hospital, University Medical Center Ljubljana

Ljubljana, Slovenia

Location

MeSH Terms

Interventions

2'-((4'-trifluoromethanesulfonyloxy)phenyl)-N-methanesulfonylpropionamide; Interleukin-8; Receptors, Interleukin-8B

Intervention Hierarchy (Ancestors)

Chemokines, CXC; Chemokines; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Interleukins; Proteins; Chemotactic Factors; Biological Factors; Inflammation Mediators; Receptors, Interleukin-8; Receptors, CXCR; Receptors, Chemokine; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Cytokine; Receptors, Immunologic; Receptors, Interleukin

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 9, 2020
• First Posted: November 13, 2020
• Study Start: January 12, 2021
• Primary Completion: March 31, 2025
• Study Completion: October 21, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IL (3); US (25); SE (5); BE (3); SL (1); DE (6); GE (4); IT (10)