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Trial record 2 of 3 for:    MEX0114

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

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ClinicalTrials.gov Identifier: NCT04899271
Recruitment Status : Recruiting
First Posted : May 24, 2021
Last Update Posted : May 24, 2021
Sponsor:
Information provided by (Responsible Party):
Dompé Farmaceutici S.p.A

Brief Summary:

The objectives of this clinical trial are:

  • to evaluate whether a 12 month treatment with ladarixin is effective to improve glycemic control in newly diagnosed T1D adult patients with preserved beta-cell function.
  • to evaluate the safety of ladarixin in the specific clinical setting

Condition or disease Intervention/treatment Phase
New-onset Type 1 Diabetes Drug: Ladarixin Other: Placebo Phase 2

Detailed Description:

The study is a phase 2, multicenter, double-blind, placebo-controlled study. It will randomize approximately 75 adult patients with new-onset type 1 diabetes (T1D) and preserved beta-cell function (fasting C-peptide >0.205 nmol/l) at baseline. Patients will be 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 18 months from the 1st administration of the study medication. The study database will be locked and data analyzed when the last patient randomized has completed month 12 follow-up visit. After this time point, the follow-up will continue under open-label conditions up to month 18,

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Appearance, including packaging and labelling, of the IMP (capsules, packaging) will not allow to recognize actual treatment (either ladarixin or placebo).
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of 400 mg Twice a Day Oral Ladarixin in Patients With New-onset Type 1 Diabetes and Preserved Beta-cell Function at Baseline.
Actual Study Start Date : December 14, 2020
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: Ladarixin
The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off)
Drug: Ladarixin
400 mg b.i.d. for 13 cycles of 14 days on/14 days off
Other Name: LDX

Placebo Comparator: Placebo
The control group will receive matched placebo
Other: Placebo
Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding




Primary Outcome Measures :
  1. Proportion of patients with HbA1c <7% and daily insulin requirement <0.50 IU/Kg/day [ Time Frame: 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.



Secondary Outcome Measures :
  1. Proportion of patients with HbA1c < 7% and daily insulin requirement <0.50 IU/Kg/day [ Time Frame: Months 6 and 18 ]
    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). Follow-up is extended up to 18 months to evaluate the potential persistency of any glycemic benefit.

  2. Proportion of patients with a reduction in HbA1c% > 0.5% from baseline and daily insulin requirement <0.50 IU/Kg [ Time Frame: Months 6, 12 and 18 ]
    Proportion of patients with a reduction in HbA1c% > 0.5% from baseline and daily insulin requirement <0.50 IU/Kg/day was calculated

  3. 2-hour AUC of C-peptide response to the MMTT [ Time Frame: Months 6, 12 and 18 ]

    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 a 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 Months 6, 12 and 18.


  4. Time in range (TIR) by Continuous Glucose Monitoring (CGM) [ Time Frame: Months 6, 12 and 18 ]

    Continuous glucose monitors (CGM) continually monitors glucose plasma levels through an external device that's attached to the body, and gives real-time updates.Time in range is the amount of time the patient spends in the target blood sugar (blood glucose) range-between 70 and 180 mg/dL for most people.

    The time in range method works with the individual CGM's data by looking at the amount of time blood sugar has been in target range and the times it has been high (hyperglycemia) or low (hypoglycemia).

    This data is helpful in finding out which types of foods and what activity level causes patient's blood sugar to rise and fall.


  5. HbA1c levels [ Time Frame: Months 6, 12 and 18 ]

    HbA1c measurement can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement.

    An HbA1c of 6.5% is recommended as the cut point for diagnosing diabetes. A value of less than 6.5% does not exclude diabetes diagnosed using glucose tests.


  6. Proportion of patients with HbA1c < 7% who did not experience severe hypoglycemic events during treatment [ Time Frame: Months 6, 12 and 18 ]
    For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.

  7. Additional Glucose Variability Indices derived from CGM: PPG [ Time Frame: Months 6, 12 and 18 ]
    PPG=2-hour postprandial glucose. All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System

  8. Additional Glucose Variability Indices derived from CGM: MAGE [ Time Frame: Months 6, 12 and 18 ]
    MAGE=Mean Amplitude Glycemic Excursions. All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System.

  9. Additional Glucose Variability Indices derived from CGM: CONGA-n [ Time Frame: Months 6, 12 and 18 ]
    CONGA-n=continuous overall net glycemic action. All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System.

  10. Additional Glucose Variability Indices derived from CGM: MODD [ Time Frame: Months 6, 12 and 18 ]
    MODD=Mean Of the Daily Differences. All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System.

  11. Additional Glucose Variability Indices derived from CGM: mean daily blood glucose [ Time Frame: Months 6, 12 and 18 ]
    All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System.

  12. Additional Glucose Variability Indices derived from CGM: Standard Deviation (SD) [ Time Frame: Months 6, 12 and 18 ]
    All these glycemic variability indices refer to the intra-day or inter-day values and differences derived from the glucose values (these latter expressed in mg/dL) collected index by index using continuous glucose monitoring (CGM) System.

  13. Number of self-reported episodes of severe hypoglycemia [ Time Frame: Months 6, 12 and 18 ]
    For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.

  14. Average (previous 3 days) daily insulin requirements (IU/kg/day) [ Time Frame: Months 6, 12 and 18 ]

    For the purpose of this study, daily insulin is averaged over the previous 3 days.Insulin requirement (IU/kg/day averaged over the previous 3 days) was to be recorded to Months 6, 12 and 18.

    Patients were admitted to intensive diabetes management, according to current ADA recommendation [2014]. Patients were instructed to self-monitor their glucose values at least 4 times a day and to report (glucose meter/log) outcome to the diabetes management team. Insulin intake was adjusted to target HbA1c levels of less than 7% and self-monitored (fingerstick):

    • pre-prandial blood glucose of 70-130 mg/dL
    • post-prandial blood glucose < 180 mg/dL
    • bed-time blood glucose of 110-150 mg/dL

  15. Estimated Glucose Disposal Rate (eGDR) [ Time Frame: Months 6, 12 and 18 ]
    Estimated Glucose Disposal Rate (eGDR) is a marker for the Assessment of Insulin Resistance and a validated clinical tool for estimating insulin sensitivity in type 1 diabetes.

  16. Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Throughout the study up to 18 months ]

    An AE is any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the trial intervention.

    A serious adverse event is an adverse event that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 ant hepatitis A virus (immunoglobulin M), hepatitis B surface antigen, or ant 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04899271


Contacts
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Contact: Flavio Mantelli, MD +39 02 583831 info@dompe.com
Contact: Anna Rita Maurizi, MD +39 02 583831 info@dompe.com

Locations
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Georgia
Aleksandre Aladashvili Clinic LLC Active, not recruiting
Tbilisi, Georgia, 48102
National Center for Diabetes Research LTD Active, not recruiting
Tbilisi, Georgia, 48159
National Institute of Endocrinology LTD Active, not recruiting
Tbilisi, Georgia, 48159
Tbilisi Heart and Vascular Clinic LTD Active, not recruiting
Tbilisi, Georgia, 48159
Germany
Institut fuer Diabetes forschung in Muenster (IDFM) Active, not recruiting
Muenster, Germany, 48145
Italy
Azienda Ospedaliero-Universitaria Conzorziale Policlinico di Bari Active, not recruiting
Bari, Italy, 70124
U.O.C. di Malattie del Metabolismo, Dipartimento di scienze della salute, Università degli Studi Magna Graecia di Catanzaro, Universitaria Mater Recruiting
Catanzaro, Italy, 88100
Contact: Concetta Irace, MD       irace@unicz.it   
Ospedale Pediatrico G. Salesi - Centro Regionale di Diabetologia Clinica Pediatrica Active, not recruiting
Palermo, Italy, 90127
Università Campus Bio-Medico di Roma (UCBM) Recruiting
Roma, Italy, 00128
Contact: Paolo Pozzilli, Professor       p.pozzilli@unicampus.it   
UOD di Diabetologia, Azienda Ospedaliera-Universitaria Recruiting
Rome, Italy, 00161
Contact: Raffaella Buzzetti, MD       raffaella.buzzetti@uniroma1.it   
Sponsors and Collaborators
Dompé Farmaceutici S.p.A
Investigators
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Study Director: Flavio Mantelli, MD Dompé Farmaceutici
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Responsible Party: Dompé Farmaceutici S.p.A
ClinicalTrials.gov Identifier: NCT04899271    
Other Study ID Numbers: LDX0419
2020-002966-15 ( EudraCT Number )
First Posted: May 24, 2021    Key Record Dates
Last Update Posted: May 24, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dompé Farmaceutici S.p.A:
Type 1 diabetes
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases