A Study to Assess Efficacy/Safety of Ladarixin in Type 1... | NCT04899271

ID	Type	Description	Link
2020-002966-15	EudraCT Number

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Ladarixin	Drug	400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Ladarixin

Measure	Description	Time Frame
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)

Measure	Description	Time Frame
Number of Patients With HbA1c < 7% and Daily Insulin Requirement <0.50 IU/Kg/Day at 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. Please note that "proportion" is expressed as "count" (number + % of participants)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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;
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);
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).

Name	Affiliation	Role
Enrico M Minnella, MD	Dompé Farmaceutici	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Colorado School of Medicine - Barbara Davis Center for Childhood Diabetes (BDC) - Specialty Clinic		Aurora	Colorado	80045	United States

ID	Title	Description
FG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
FG001	Placebo

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 30, 2020	Dec 9, 2024

ID	Title	Description
BG000	Ladarixin	The treatment group received 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
BG001	Placebo	The control group received matched placebo Placebo: Placebo was administered orally with the same scheme of administration of LDX to preserve blinding
BG002	Total	Total of all reporting groups

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

Number of Patients With HbA1c <7% and Daily Insulin Requirement <0.50 IU/Kg/Day at Month 12

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)

FAS: The Full Analysis Set consisted of all randomized patients who received at least one dose of the IMP (either ladarixin or placebo). The FAS was analyzed according to the ITT principle, i.e., by treatment allocation regardless happening of intercurrent events (treatment policy strategy). The FAS was used for the primary analyses of the study and to present results on efficacy data.

Posted

Count of Participants

Participants

Month 12 (52±2 weeks)

ID	Title	Description
OG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
OG001	Placebo	The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding

Units	Counts
Participants	OG00018 OG0017

Title

Denominators

Categories

Title	Measurements
	OG00011 OG0015

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Chi-squared		0.807														Superiority

Secondary

Number of Patients With HbA1c < 7% and Daily Insulin Requirement <0.50 IU/Kg/Day at 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. Please note that "proportion" is expressed as "count" (number + % of participants)

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
OG001	Placebo	The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding

Secondary

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

The number of patients with a reduction in HbA1c% > 0.5% from baseline and daily insulin requirement <0.50 IU/Kg/day was calculated at the hereunder specified timepoints.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
OG001	Placebo	The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding

Units	Counts

Secondary

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

C-peptide level is a widely used measure of pancreatic beta-cell function and the MMTT is one of the methods for its estimation. AUC stands for Area Under the Curve.

AUC calculation was based on actual rather scheduled timings and it was calculated using the trapezoidal rule. C-peptide 0-120 min AUC (nmol/L) values were calculated based on all Basal-120min C-peptide values. Unscheduled assessments were excluded from the analysis.

FAS (Full Analysis Set): all randomized patients who received at least one dose of the IMP (either ladarixin or placebo), analyzed according to the ITT principle. Discrepancies between Overall Number of Participants Analyzed and Number Analyzed for Ladarixin group due to: at Month 6: 2 participants withdrew their consent; at Month 12: 1 additional participant was lost at follow-up (who remained lost at follow-up even for Month 18 visit).

Posted

Mean

Standard Deviation

nmol/L

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

ID	Title	Description
OG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
OG001	Placebo	The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding

Secondary

Changes From Baseline in Percentage Glycated Hemoglobin (HbA1c) Levels at 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. An A1C test measures the percentage of red blood cells that have glucose-coated hemoglobin.

FAS (Full Analysis Set): all randomized patients who received at least one dose of the IMP (either ladarixin or placebo), analyzed according to the ITT principle. Discrepancies between Overall Number of Participants Analyzed and Number Analyzed in both arms are due to participants withdrawing consent or with blood samples not collected at timepoints or lost at follow-up.

Posted

Mean

Standard Deviation

percentage HbA1c

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

ID	Title	Description
OG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
OG001	Placebo	The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding

Secondary

Number of Patients With HbA1c < 7% Who Did Not Experience Severe Hypoglycemic Events During Treatment at 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.

FAS (Full Analysis Set): all randomized patients who received at least one dose of the IMP (either ladarixin or placebo), analyzed according to the ITT principle. Discrepancies between Overall Number of Participants Analyzed and Number Analyzed in both arms are due to participants withdrawing consent or with blood samples not collected at timepoints or lost at follow-up.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
OG001	Placebo	The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding

Secondary

Overall Number of Self-reported Episodes of Severe Hypoglycemia

FAS: The Full Analysis Set consisted of all randomized patients who received at least one dose of the IMP. The FAS was analyzed according to the ITT principle, i.e., by treatment allocation regardless happening of intercurrent events (treatment policy strategy). The FAS was used for the primary analyses of the study and to present results on efficacy data.

Posted

Number

total number of severe hypoglyc episodes

From baseline to study termination (month 18, week 78)

ID	Title	Description
OG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
OG001	Placebo	The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding

Secondary

Blood Glucose Levels for Patients Reporting Severe Hypoglycemia at Months 6, 12 and 18

A severe hypoglycemic event was defined as an event with 1 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 or prompt recovery after oral carbohydrate, i.e. glucose, or glucagon administration. Summary statistics of blood glucose level (mg/dL) are provided by treatment group at each time point for patients reporting severe hypoglycemia.

Posted

Mean

Standard Deviation

mg/dL

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

ID	Title	Description
OG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
OG001	Placebo	The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding

Secondary

Change From Baseline in Average (Previous 3 Days) Daily Insulin Requirements (IU/kg/Day) at 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

FAS (Full Analysis Set): all randomized patients who received at least one dose of the IMP (either ladarixin or placebo), analyzed according to the ITT principle. Discrepancies between Overall Number of Participants Analyzed and Number Analyzed in both arms are due to participants withdrawing consent or with blood samples not collected at timepoints or lost at follow-up

Posted

Mean

Standard Deviation

IU/kg/day

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

ID	Title	Description
OG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
OG001	Placebo

Secondary

Change From Baseline in Estimated Glucose Disposal Rate (eGDR) at 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.

FAS (Full Analysis Set): all randomized patients who received at least one dose of the IMP (either ladarixin or placebo), analyzed according to the ITT principle. Discrepancies between Overall Number of Participants Analyzed and Number Analyzed in both arms are due to participants withdrawing consent or with blood samples not collected at timepoints or lost at follow-up.

Posted

Mean

Standard Deviation

mg/kg/min

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

ID	Title	Description
OG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
OG001	Placebo	The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding

Units	Counts

Secondary

Number of Patients With at Least One Adverse Events (AEs), Serious or Not Serious

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.

SAF population: The Safety (SAF) population consisted of all randomized patients who received at least one dose of the IMP. The SAF population was analyzed according to the actual treatment received and was used to present results on safety data.

Posted

Count of Participants

Participants

Throughout the study up to 18 months

ID	Title	Description
OG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off
OG001	Placebo	The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding

Units	Counts

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
COVID-19	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0006 events6 affected18 at risk EG0015 events5 affected7 at risk
Nasopharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0005 events2 affected18 at risk EG0011 events1 affected7 at risk
Influenza	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Nasal herpes	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Streptococcal urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected7 at risk
Vulvovaginal candidiasis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected7 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0010 events0 affected7 at risk
Abnormal faeces	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Irritable bowel syndrome	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
abdominal pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected7 at risk
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0013 events3 affected7 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0010 events0 affected7 at risk
Hypoglycemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0008 events2 affected18 at risk EG0011 events1 affected7 at risk
Autoimmune thyroiditis	Endocrine disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0011 events1 affected7 at risk
Hyperparathyroidism primary	Endocrine disorders	MedDRA 23.0	Systematic Assessment	EG0003 events1 affected18 at risk EG0010 events0 affected7 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Post procedural hypothyroidism	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected18 at risk EG0010 events0 affected7 at risk
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events2 affected7 at risk
Parosmia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected7 at risk
Sciatica	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected7 at risk
Taste disorders	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected7 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected7 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected7 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected7 at risk
Normocytic anemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Vision blurred	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Occult blood	Investigations	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected18 at risk EG0010 events0 affected7 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Dysmenorrhea	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected7 at risk
Amenorrhea	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected7 at risk
Vulvovaginal pruritus	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0012 events1 affected7 at risk
Fixed eruption	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected18 at risk EG0010 events0 affected7 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected7 at risk
Wisdom teeth removal	Surgical and medical procedures	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected18 at risk EG0010 events0 affected7 at risk
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected7 at risk

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

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ladarixin	The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	0	18	1	18	12	18
EG001	Placebo	The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding	0	7	0	7	5	7