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

NCT04899271 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: LDX04192020-002966-15
• Study Type: interventional
• Target: 25
• Locations: 6 countries
• Sites: 16

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.

Conditions

New-onset Type 1 Diabetes

Keywords

Type 1 diabetes

Outcome Measures

Primary Outcomes (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)

  Month 12 (52±2 weeks)

Secondary Outcomes (10)

• Number of Patients With HbA1c < 7% and Daily Insulin Requirement <0.50 IU/Kg/Day at Months 6 and 18

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

• 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

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

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

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

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

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

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

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

Study Arms (2)

Ladarixin

EXPERIMENTAL

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

Drug: Ladarixin

Placebo

PLACEBO COMPARATOR

The control group received matched placebo

Other: Placebo

Interventions

Ladarixin DRUG

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

Also known as: LDX

Ladarixin

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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;
• 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).

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (16)

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

Aurora, Colorado, 80045, United States

Location

Atlanta Diabetes Associates (ADA)

Atlanta, Georgia, 30318, United States

Location

Universitair Ziekenhuis Brussel (UZB)

Jette, Belgium

Location

National Center for Diabetes Research LTD

Tbilisi, 48159, Georgia

Location

National Institute of Endocrinology LTD

Tbilisi, 48159, Georgia

Location

Universitaetsklinikum Gessen und Marburg GmbH - Medizinische Klinik und Poliklinik III

Glessen, 35392, Germany

Location

St. Josefskrankenhaus Diabestesinstitut Heidelberg

Heidelberg, 69115, Germany

Location

Institut fuer Diabetes forschung in Muenster (IDFM)

Münster, 48145, Germany

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, 88100, Italy

Location

Universitá degli Studi di Milano - Ospedale Luigi Sacco

Milan, 20157, Italy

Location

Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"

Palermo, 90127, Italy

Location

Università Campus Bio-Medico di Roma (UCBM)

Roma, 00128, Italy

Location

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

Rome, 00161, Italy

Location

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

Belgrade, 11000, Serbia

Location

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

Kragujevac, 34000, Serbia

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

2'-((4'-trifluoromethanesulfonyloxy)phenyl)-N-methanesulfonylpropionamide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

The enrolment was stopped on March,28, 2022 due to low enrolment rate at the randomization of the 25th patient. Due to the trial early termination, efficacy analyses were reduced given the limited sample size of the study vs with the one expected.

Results Point of Contact

• Title: Clinical Development and Operations
• Organization: Dompé Farmaceutici SpA

clinical.trials@dompe.com

+39 (0) 583831

Study Officials

• Enrico M Minnella, MD

  Dompé Farmaceutici

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Appearance, including packaging and labelling, of the IMP (capsules, packaging) will not allow to recognize actual treatment (either ladarixin or placebo).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 24, 2021
• Study Start: December 14, 2020
• Primary Completion: April 27, 2023
• Study Completion: October 11, 2023
• Last Updated: May 14, 2025
• Results First Posted: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); SE (2); US (2); BE (1); IT (6); GE (2)