A Phase 2, Multicentre, Randomized, Double-blind, Placebo-controlled Study in Patients With New-onset Type 1 Diabetes

NCT02814838 | Completed Phase 2 Results

• 2 other identifiers: MEX01142014-003968-20
• Study Type: interventional
• Target: 76
• Locations: 3 countries
• Sites: 8

Brief Summary

The objective of this clinical trial is to investigate whether ladarixin has sufficient activity (preservation of β-cell function and slow-down of the progression of T1D) to warrant its further development (proof of concept trial). The safety of ladarixin in the specific clinical setting will be also evaluated. The study is a phase 2, multicentre, double-blind study. 72 patients with new-onset type 1 diabetes (T1D) were planned to be involved, randomly (2:1) assigned to receive either ladarixin treatment (400 mg b.i.d. for 3 cycles of 14 days on/14 days off - treatment group) or placebo (control group). Recruitment was competitive among the study sites, until the planned number of patients was enrolled. A total of 76 patients were actually recruited.

Conditions

Diabetes Mellitus, Insulin-Dependent

Keywords

Diabetes mellitus Type 1; Beta cells function

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve (AUC)(0-2 h) of C-peptide Response to the Mixed Meal Tolerance Test (MMTT) at Week 13

  C-peptide level is a widely used measure of pancreatic beta-cell function. The MMTT is one of the methods for its estimation. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each follow-up visit on weeks 13±1, 26±2, and 52±2. Prior to the test, patients withheld long-acting insulin on the morning of the test. Rapid-acting and short-acting insulin were allowed up to 6hrs and 2 hrs, respectively, before the test. The test was rescheduled if the patient had a capillary glucose value of \>200mg/dL or \<70mg/dL. After 2 pre-meal basal samples had been drawn between -20 to 0 min (basal 1 and basal 2), patients were given 6mL/kg of Boost® High Protein Nutritional Drink up to a maximum of 360mL, to be drunk within 5 min. Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal at week 13+/-1 The 2-hour C-peptide AUC after the MMTT at Week 13±1 was transformed as log(x+1) values.

  week 13±1

Secondary Outcomes (13)

• Area Under the Curve (AUC) (0-2 h) of C-peptide Response to the Mixed Meal Tolerance Test (MMTT) at Weeks 26 and 52

  Follow-ups at Weeks 26±2 and 52±2

• Percent Change From Baseline of 2-hour AUC of C-peptide Response to the MMTT

  Follow-ups at Weeks 13±1, 26±2 and 52±2

• Change From Screening in Average (Previous 3 Days) Insulin Requirement

  Follow-ups at Weeks 13±1, 26±2 and 52±2

• Change From Screening in Glycated Haemoglobin (HbA1c) Levels

  Follow-ups at Weeks 13±1, 26±2 and 52±2

• Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT

  Baseline, follow-ups at Weeks 13±1, 26±2, and 52±2

Study Arms (2)

Ladarixin

EXPERIMENTAL

Ladarixin oral capsule

Drug: Ladarixin

Placebo

PLACEBO COMPARATOR

Placebo oral capsule

Drug: Placebo

Interventions

Ladarixin DRUG

Ladarixin oral capsule

Also known as: Active treatment

Ladarixin

Placebo DRUG

Placebo oral capsule

Also known as: Placebo treatment

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 (randomization 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);
• Residual β-cell function as per peak stimulated (MMTT) C-peptide level \>0.6ng/mL (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.

You may not qualify if:

• Patients taking twice daily pre-mixed insulin or on insulin pump;
• 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 calculated creatinine clearance (CLcr) \< 60 mL/min according to the Cockcroft-Gault formula (Cockcroft-Gault, 1976);
• 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;
• Complete Left Bundle Branch Block (LBBB), atrio-ventricular block (mobitz II 2nd degree or 2:1 atrio-ventricular block), complete heart block;
• Electronic pacemaker positioned or implanted defibrillator;
• History of significant cardiovascular disease;
• Known hypersensitivity to non-steroidal antiinflammatory drugs;
• Concomitant treatment with 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 metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin, or any medications known to influence glucose tolerance (e.g. β-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;
• 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 an 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 (8)

Universitair Ziekenhuis Brussel Diabetes Clinic

Brussels, 1090, Belgium

Location

Universitair Ziekenhuis Leuven Campus Gasthuisberg Endocrinology

Leuven, 3000, Belgium

Location

Med. Klinik und Poliklinik 3, Universitätsklinikum Giessen und Marburg GmbH

Giessen, 32392, Germany

Location

Zentrum für Diabetes und Gefäßerkrankungen

Münster, 48145, Germany

Location

Università Aldo Moro-Ospedale Policlinico

Bari, 70124, Italy

Location

Presidio Policlinico di Monserrato

Cagliari, 88554, Italy

Location

Internal Medicine - Diabetes & Endocrinology Unit, San Raffaele Hospital Milan

Milan, 20132, Italy

Location

Unità Operativa Complessa di Endocrinologia e Dialettologia. Università Campus Bio-Medico di Roma

Rome, 00128, Italy

Location

Related Publications (1)

• Sordi V, Monti P, Lampasona V, Melzi R, Pellegrini S, Keymeulen B, Gillard P, Linn T, Bosi E, Rose L, Pozzilli P, Giorgino F, Cossu E, Piemonti L. Post hoc analysis of a randomized, double-blind, prospective trial evaluating a CXCR1/2 inhibitor in new-onset type 1 diabetes: endo-metabolic features at baseline identify a subgroup of responders. Front Endocrinol (Lausanne). 2023 Jun 20;14:1175640. doi: 10.3389/fendo.2023.1175640. eCollection 2023.

  PMID: 37409229 DERIVED

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

Results Point of Contact

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

clinical.trials@dompe.com

+39 02 583831

Study Officials

• Emanuele Bosi, MD

  Internal Medicine - Diabetes & Endocrinology Unit, San Raffaele Hospital Milan

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2016
• First Posted: June 28, 2016
• Study Start: August 1, 2016
• Primary Completion: May 15, 2019
• Study Completion: May 15, 2019
• Last Updated: April 19, 2024
• Results First Posted: January 12, 2021

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); BE (2); IT (4)