A Phase 2, Multicentre, Randomized, Double-blind, Placebo-controlled Study in Patients With New-onset Type 1 Diabetes
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|ClinicalTrials.gov Identifier: NCT02814838|
Recruitment Status : Active, not recruiting
First Posted : June 28, 2016
Last Update Posted : June 13, 2018
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 will be a phase 2, multicentre, double-blind study. It will involve 72 patients with new-onset type 1 diabetes (T1D), 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 will be competitive among the study sites, until the planned number of patients is enrolled.
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus, Insulin-Dependent||Drug: Ladarixin Drug: Placebo||Phase 2|
T1D is an organ-specific autoimmune disease in which the immune system attacks the insulin-producing β-cells. The onset of the disease typically occurs before adulthood and seriously affects a person's quality of life.
T1D is treated with life-long daily exogenous insulin injections and monitoring of blood glucose levels. However, even optimization of glucose control through the most recent technologies cannot adequately substitute for the finely tuned normal balance of the glucose levels. Therefore, despite marked improvements in diabetes care in recent years, insulin-dependent diabetes results in secondary long-term complications and is one of the leading causes of end-stage renal disease, blindness and amputation. Additionally, hypoglycaemia unawareness is a serious consequence of recurrent hypoglycaemia often requiring emergency care.
Maintenance of residual β-cell function (as measured by C-peptide response) was demonstrated to be associated with reduced rate of microvascular complications and hypoglycaemia, improved quality of life, and overall reduction in morbidity and associated management costs. Therefore, pharmacological approaches aimed at controlling the autoimmune response and restoring self-tolerance to pancreatic β-cells had attracted the clinical/scientific interest.
Among these, rituximab, CD3-specific monoclonal antibodies, GAD65, DiaPep277 have progressed to phase III clinical trials. Other agents, including cytokines modulators such as anti-TNF or anti-IL1, are under clinical evaluation. Unfortunately, even if safe preservation of β-cell function and improvement of glycaemic control have been evidenced for some of the pharmacological approaches evaluated so far, none has been definitely approved for the "treatment" of diabetes onset. New strategies are being evaluated which combine agents targeting sequential arms of the immune and inflammatory response involved in β-cell disruption. In this regard, IL-8 appears to be an important mediator in the progression of type 1 diabetes. Production and secretion of pro-inflammatory IL-8 has been demonstrated from human pancreatic islets upon enterovirus infections, and LPS-induced production of IL-8 by neutrophils is increased in type 1 pre-diabetic and diabetic patients. In parallel, circulating levels of IL-8 were elevated in children with T1D compared to non-diabetic controls. Specifically, levels of IL-8 correlate with glycaemic control, higher level being associated to poorer or unfavorable glucose control.
As a result of these findings, the modulation or inhibition of IL8 activity is considered a valid target for the development of innovative treatments aimed to control the progression of T1D.
Results obtained with ladarixin in mouse models of T1D, and particularly reversal of "diabetes" in the NOD mice, clearly shows the ability of this CXCR1/2 inhibitor to protect β-cells and either prevent or delay the progression of hyperglycaemia. The positive effects of ladarixin, coupled with the safety shown in phase 1 studies, provide a sound rationale for a clinical study aimed at evaluating the effect of ladarixin in patients with new onset diabetes and supports the conduct of the present study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||72 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Phase 2, Multicentre, 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|
|Actual Study Start Date :||August 2016|
|Estimated Primary Completion Date :||April 2019|
|Estimated Study Completion Date :||September 2019|
Ladarixin oral capsule
Ladarixin oral capsule
Other Name: Active treatment
Placebo Comparator: Placebo
Placebo oral capsule
Placebo oral capsule
Other Name: Placebo treatment
- AUC of C-peptide [ Time Frame: week 13±1 ]2-hour AUC of C-peptide response to the MMTT
- AUC of C-peptide [ Time Frame: Baseline ]2-hour AUC of C-peptide response to the MMTT
- AUC of C-peptide [ Time Frame: week 26±2 ]2-hour AUC of C-peptide response to the MMTT
- AUC of C-peptide [ Time Frame: week 52±2 ]2-hour AUC of C-peptide response to the MMTT
- Insulin requirement [ Time Frame: baseline ]Average (previous 3 days) insulin requirement
- Insulin requirement [ Time Frame: week 13±1 ]Average (previous 3 days) insulin requirement
- Insulin requirement [ Time Frame: week 26±2 ]Average (previous 3 days) insulin requirement
- Insulin requirement [ Time Frame: week 52±2 ]Average (previous 3 days) insulin requirement
- HbA1c [ Time Frame: baseline ]HbA1c levels
- HbA1c [ Time Frame: week 13±1 ]HbA1c levels
- HbA1c [ Time Frame: week 26±2 ]HbA1c levels
- HbA1c [ Time Frame: week 52±2 ]HbA1c levels
- Cumulative severe hypoglycaemic events [ Time Frame: week 13±1 ]Cumulative severe hypoglycaemic events occurring from randomization
- Cumulative severe hypoglycaemic events [ Time Frame: week 26±2 ]Cumulative severe hypoglycaemic events occurring from randomization
- Cumulative severe hypoglycaemic events [ Time Frame: week 52±2 ]Cumulative severe hypoglycaemic events occurring from randomization
- Adverse Events [ Time Frame: week 52±2 ]Adverse Events during the study period
- Serious Adverse Events [ Time Frame: week 52±2 ]Adverse Events during the study period
- Vital signs [ Time Frame: week 4 ]Changes in Blood Pressure and Heart Rate from screening
- Vital signs [ Time Frame: week 13 ]Change in Blood Pressure and Heart Rate from screening
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): NCT02814838
|Universitair Ziekenhuis Brussel Diabetes Clinic|
|Brussels, Belgium, 1090|
|Universitair Ziekenhuis Leuven Campus Gasthuisberg Endocrinology|
|Leuven, Belgium, 3000|
|Med. Klinik und Poliklinik 3, Universitätsklinikum Giessen und Marburg GmbH|
|Giessen, Germany, 32392|
|Zentrum für Diabetes und Gefäßerkrankungen|
|Münster, Germany, 48145|
|Università Aldo Moro-Ospedale Policlinico|
|Bari, Italy, 70124|
|Presidio Policlinico di Monserrato|
|Cagliari, Italy, 88554|
|Internal Medicine - Diabetes & Endocrinology Unit, San Raffaele Hospital Milan|
|Milan, Italy, 20132|
|Unità Operativa Complessa di Endocrinologia e Dialettologia. Università Campus Bio-Medico di Roma|
|Rome, Italy, 00128|
|Principal Investigator:||Emanuele Bosi, MD||Internal Medicine - Diabetes & Endocrinology Unit, San Raffaele Hospital Milan|