Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2014-003968-20 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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 showed 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, provided a sound rationale for a clinical study aimed at evaluating the effect of ladarixin in patients with new onset diabetes and supported the conduct of the present study.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ladarixin | Experimental | Ladarixin oral capsule |
|
| Placebo | Placebo Comparator | Placebo oral capsule |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ladarixin | Drug | Ladarixin oral capsule |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC) (0-2 h) of C-peptide Response to the Mixed Meal Tolerance Test (MMTT) at Weeks 26 and 52 | 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Emanuele Bosi, MD | Internal Medicine - Diabetes & Endocrinology Unit, San Raffaele Hospital Milan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitair Ziekenhuis Brussel Diabetes Clinic | Brussels | 1090 | Belgium | |||
| Universitair Ziekenhuis Leuven Campus Gasthuisberg Endocrinology |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37409229 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Ladarixin | Ladarixin oral capsule Ladarixin: Ladarixin oral capsule |
| FG001 | Placebo | Placebo oral capsule Placebo: Placebo oral capsule |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 3, 2020 | Nov 4, 2020 |
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Placebo oral capsule |
|
|
| Follow-ups at Weeks 26±2 and 52±2 |
| Percent Change From Baseline of 2-hour AUC of C-peptide Response to the MMTT | 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. The test was initiated before 10 a.m. 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 (Nestlé Nutrition) up to a maximum of 360mL, to be drunk within 5 min. Post-meal samples were drawn at 15±5, 30±5, 60±10, 90±10, 120±15, 180±15 min after the meal. | Follow-ups at Weeks 13±1, 26±2 and 52±2 |
| Change From Screening in Average (Previous 3 Days) Insulin Requirement | Insulin requirement (IU/kg/day averaged over the previous 3 days) was to be recorded in the interval from randomization to Week 13±1, Week 13±1 to Week 26±2, and Week 26±2 to Week 52±2. From enrolment, 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):
| Follow-ups at Weeks 13±1, 26±2 and 52±2 |
| Change From Screening in Glycated Haemoglobin (HbA1c) Levels | 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. | 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 | Time points at each visit are Basal 1 and Basal 2 (samples collected at -20 and 0 min, respectively; Here are reported the following timepoints: Basal average (which is the average of Basal 1 and Basal 2), 15, 30, 60, 90, 120, and 180 minutes after the meal. For values at each time point see below. | Baseline, follow-ups at Weeks 13±1, 26±2, and 52±2 |
| Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT | Time points at each visit are Basal 1 and Basal 2 (samples collected at -20 and 0 min, respectively). Here are reported the following timepoints: Basal average (which is the average of Basal 1 and Basal 2), 15, 30, 60, 90, 120, and 180 minutes after the meal. For values at each time point see below. | Baseline, follow-ups at Weeks 13±1, 26±2, and 52±2 |
| Cumulative Severe Hypoglycaemic Events Occurring From Randomisation by Visit | A severe hypoglycaemic event was defined as an event with one of the following symptoms: "memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration. | Follow-ups at Weeks 13±1, 26±2 and 52±2 |
| Proportion of Patients Maintaining a Residual β-cell Function | Maintenance of a residual ß-cell function is defined as at least one MMTT C-peptide value > 0.2 nmol/L. Proportion is reported as Percentage of patients. | Follow-ups at Weeks 13±1, 26±2 and 52±2 |
| Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit | A severe hypoglycaemic event was defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration. Proportion is reported as percentage of patients. Events per patient are calculated from the date of randomisation. | Follow-ups at Weeks 13±1, 26±2 and 52±2 |
| C-peptide AUC(15 to 120 Mins) Above Fasting Value | The means are all "adjusted means". The MMTT over the study: logAUC(15-120 min) of C-peptide above fasting value at Weeks 13±1, 26±2, and 52±2 is reported. Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal at weeks 13+/-1, 26±2 and 52±2 | Follow-ups at Weeks 13±1 26±2 and 52±2 |
| Area Under the Curve (AUC) (0-2 h) of C-peptide MMTT in Patients With Screening C-peptide < Median Value | A subgroup analysis of efficacy endpoints by fasting C-peptide at Screening was performed. The reported data specifically refers to fasting C-peptide at Screening \ | Follow-up at Weeks 13±1, 26±2, and 52±2. |
| Area Under the Curve (AUC) (15-120 Min) of C-peptide MMTT Above Fasting Value in Patients With Screening C-peptide < Median Value | A subgroup analysis of efficacy endpoints by fasting C-peptide at Screening was performed. The reported data specifically refers to fasting C-peptide at Screening \ | Follow-up at Weeks 13±1, 26±2, and 52±2. |
| Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit in Patients With Screening C-peptide < Median Value | A severe hypoglycaemic event was defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration. Proportion is reported as percentage of patients, despite the measure type indicated is "number". Events per patient are calculated from the date of randomisation. | Follow-up at Weeks 13±1, 26±2, and 52±2 |
| Leuven |
| 3000 |
| Belgium |
| Med. Klinik und Poliklinik 3, Universitätsklinikum Giessen und Marburg GmbH | Giessen | 32392 | Germany |
| Zentrum für Diabetes und Gefäßerkrankungen | Münster | 48145 | Germany |
| Università Aldo Moro-Ospedale Policlinico | Bari | 70124 | Italy |
| Presidio Policlinico di Monserrato | Cagliari | 88554 | Italy |
| Internal Medicine - Diabetes & Endocrinology Unit, San Raffaele Hospital Milan | Milan | 20132 | Italy |
| Unità Operativa Complessa di Endocrinologia e Dialettologia. Università Campus Bio-Medico di Roma | Rome | 00128 | Italy |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Ladarixin | Ladarixin oral capsule Ladarixin: Ladarixin oral capsule |
| BG001 | Placebo | Placebo oral capsule Placebo: Placebo oral capsule |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo) | Posted | Mean | Standard Deviation | log(ng*hr/ml [0-2 h]+1) | week 13±1 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Area Under the Curve (AUC) (0-2 h) of C-peptide Response to the Mixed Meal Tolerance Test (MMTT) at Weeks 26 and 52 | 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. | ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics. | Posted | Mean | Standard Deviation | log(ng*hr/ml [0-2 h]+1) | Follow-ups at Weeks 26±2 and 52±2 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline of 2-hour AUC of C-peptide Response to the MMTT | 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. The test was initiated before 10 a.m. 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 (Nestlé Nutrition) up to a maximum of 360mL, to be drunk within 5 min. Post-meal samples were drawn at 15±5, 30±5, 60±10, 90±10, 120±15, 180±15 min after the meal. | ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics. | Posted | Mean | Standard Deviation | percentage of change | Follow-ups at Weeks 13±1, 26±2 and 52±2 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Screening in Average (Previous 3 Days) Insulin Requirement | Insulin requirement (IU/kg/day averaged over the previous 3 days) was to be recorded in the interval from randomization to Week 13±1, Week 13±1 to Week 26±2, and Week 26±2 to Week 52±2. From enrolment, 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):
| ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics. | Posted | Mean | Standard Deviation | IU/kg/day | Follow-ups at Weeks 13±1, 26±2 and 52±2 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Screening in Glycated Haemoglobin (HbA1c) Levels | 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. | ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics. | Posted | Mean | Standard Deviation | percentage of glycated haemoglobin | Follow-ups at Weeks 13±1, 26±2 and 52±2 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Basal to 180 Minutes Time Course of C-peptide Concentration Derived From the MMTT | Time points at each visit are Basal 1 and Basal 2 (samples collected at -20 and 0 min, respectively; Here are reported the following timepoints: Basal average (which is the average of Basal 1 and Basal 2), 15, 30, 60, 90, 120, and 180 minutes after the meal. For values at each time point see below. | ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics. | Posted | Mean | Standard Deviation | nmol/L | Baseline, follow-ups at Weeks 13±1, 26±2, and 52±2 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Basal to 180 Minutes Time Course of Glucose Concentration Derived From the MMTT | Time points at each visit are Basal 1 and Basal 2 (samples collected at -20 and 0 min, respectively). Here are reported the following timepoints: Basal average (which is the average of Basal 1 and Basal 2), 15, 30, 60, 90, 120, and 180 minutes after the meal. For values at each time point see below. | ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics. | Posted | Mean | Standard Deviation | mmol/L | Baseline, follow-ups at Weeks 13±1, 26±2, and 52±2 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Cumulative Severe Hypoglycaemic Events Occurring From Randomisation by Visit | A severe hypoglycaemic event was defined as an event with one of the following symptoms: "memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration. | ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics. | Posted | Mean | Standard Deviation | events | Follow-ups at Weeks 13±1, 26±2 and 52±2 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Patients Maintaining a Residual β-cell Function | Maintenance of a residual ß-cell function is defined as at least one MMTT C-peptide value > 0.2 nmol/L. Proportion is reported as Percentage of patients. | ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo) | Posted | Number | 95% Confidence Interval | Percentage of patients | Follow-ups at Weeks 13±1, 26±2 and 52±2 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit | A severe hypoglycaemic event was defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration. Proportion is reported as percentage of patients. Events per patient are calculated from the date of randomisation. | ITT population = all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo) | Posted | Number | 95% Confidence Interval | Percentage of patients | Follow-ups at Weeks 13±1, 26±2 and 52±2 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | C-peptide AUC(15 to 120 Mins) Above Fasting Value | The means are all "adjusted means". The MMTT over the study: logAUC(15-120 min) of C-peptide above fasting value at Weeks 13±1, 26±2, and 52±2 is reported. Post-meal samples were drawn at 15, 30, 60, 90, 120 min after the meal at weeks 13+/-1, 26±2 and 52±2 | ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics. | Posted | Mean | 95% Confidence Interval | log(ng*hr/ml [15-120 min]+1) | Follow-ups at Weeks 13±1 26±2 and 52±2 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Area Under the Curve (AUC) (0-2 h) of C-peptide MMTT in Patients With Screening C-peptide < Median Value | A subgroup analysis of efficacy endpoints by fasting C-peptide at Screening was performed. The reported data specifically refers to fasting C-peptide at Screening \ | ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics. | Posted | Mean | Standard Deviation | log(ng*hr/ml [0-2 h]+1) | Follow-up at Weeks 13±1, 26±2, and 52±2. |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Area Under the Curve (AUC) (15-120 Min) of C-peptide MMTT Above Fasting Value in Patients With Screening C-peptide < Median Value | A subgroup analysis of efficacy endpoints by fasting C-peptide at Screening was performed. The reported data specifically refers to fasting C-peptide at Screening \ | ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics. | Posted | Mean | Standard Deviation | log(ng*hr/ml [15-120 min] +1) | Follow-up at Weeks 13±1, 26±2, and 52±2. |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Patients With HbA1c <7% and Absence of Episodes of Severe Hypoglycaemia From the Previous Visit in Patients With Screening C-peptide < Median Value | A severe hypoglycaemic event was defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behaviour, irrational behaviour, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the patient was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration. Proportion is reported as percentage of patients, despite the measure type indicated is "number". Events per patient are calculated from the date of randomisation. | ITT population: all patients who were randomised and received at least 1 dose of study treatment (either ladarixin or placebo). Please note that the number of participants analysed represents the number of patients contributing to summary statistics. | Posted | Number | 95% Confidence Interval | Percentage of patients | Follow-up at Weeks 13±1, 26±2, and 52±2 |
|
AEs were recorded and reported in the CRF from enrollment throughout patient's participation in the study (last planned visit or early withdrawal date), an average of 3 years
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ladarixin | Ladarixin oral capsule Ladarixin: Ladarixin oral capsule | 0 | 50 | 3 | 50 | 37 | 50 |
| EG001 | Placebo | Placebo oral capsule Placebo: Placebo oral capsule | 0 | 26 | 1 | 26 | 21 | 26 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| mental disorder | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Eosinophilia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Lymphocytosis | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Polycythaemia | Blood and lymphatic system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Ear discomfort | Ear and labyrinth disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 19.1 | Systematic Assessment |
| |
| abdominal discomfort | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Faeces hard | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Gatroesophageal reflux disease | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hyperchlorhydria | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pancreatitis chronic | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Sensation of foreign body | General disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Eye infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Gastroeteritis viral | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Gingivitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Infected bite | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Tinea pedis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
| |
| Alcohol poisoning | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Joint injury | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Muscle injury | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Skin wound | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Sunburn | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Blood iron decreased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Eosinophil count decreased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Glycosylated haemoglobin increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Haemoglobin increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Vitamin D decreased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA 19.1 | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Migrane | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Emotional distress | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Polyuria | Renal and urinary disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Nipple inflammation | Reproductive system and breast disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Increased viscosity of upper respiratiory secretion | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Vocal cord inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
| |
| Diabetes mellitus management | Surgical and medical procedures | MedDRA 19.1 | Systematic Assessment |
| |
| Tooth extraction | Surgical and medical procedures | MedDRA 19.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 19.1 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Development & Operations | Dompé Farmaceutici SpA | +39 02 583831 | clinical.trials@dompe.com |
| Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 17, 2019 | Nov 4, 2020 | SAP_000.pdf |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C511776 | 2'-((4'-trifluoromethanesulfonyloxy)phenyl)-N-methanesulfonylpropionamide |
Not provided
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Italy |
|
| Germany |
|
Placebo oral capsule Placebo: Placebo oral capsule |
|
|
|
Placebo oral capsule
Placebo: Placebo oral capsule
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Participants |
|
|
|
| Participants |
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|