Clinical Trials Register

Summary
EudraCT Number:	2020-001926-71
Sponsor's Protocol Code Number:	LDX0319
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:	2020-09-14
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2020-001926-71

A.3

Full title of the trial

A phase 2, multicenter, randomized, double-blind, placebo-controlled study to assess the effect and safety of 400 mg twice a day oral ladarixin in patients with recent onset type 1 diabetes and a low residual β-cell function at baseline.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study to evaluate the efficacy and the safety of ladaraxin in adult and adolescent patients with recent onset type 1 diabetes

A.3.2

Name or abbreviated title of the trial where available

GLADIATOR

A.4.1

Sponsor's protocol code number

LDX0319

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/124/2020

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Dompe farmaceutici s.p.a.
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Dompe farmaceutici s.p.a.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dompe farmaceutici s.p.a.
B.5.2	Functional name of contact point	Study Medical Expert
B.5.3	Address:
B.5.3.1	Street Address	Via Santa Lucia 6
B.5.3.2	Town/ city	Milan
B.5.3.3	Post code	20122
B.5.3.4	Country	Italy
B.5.4	Telephone number	00393472676311
B.5.6	E-mail	enrico.minnella@dompe.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ladarixin
D.3.2	Product code	DF 2156A
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ladarixin
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	DF 2156A
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Recent onset Type 1 Diabetes

E.1.1.1

Medical condition in easily understood language

Type 1 Diabetes

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10067584
E.1.2	Term	Type 1 diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objective of this clinical trial is to assess whether ladarixin treatment has an effect to preserve Beta-cell function and delay the progression of T1D in adolescent and adult patients. The safety of ladarixin in the specific clinical setting will be also evaluated.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A PK sub-study is part of the trial, this has been the case since the trial start, but was not captured in the initial EudraCT form.

Pharmacokinetic endpoints will be:
- Plasma levels of 2156Y (acidic form of ladarixin) and relevant
metabolites (DF2108Y, S-isomer; DF2227Y, R-isomer) in a subset of adolescents (14-17 years, inclusive) selected for full PK analysis [Time frame: day 1 and 14, then 24, 48 and 72 hours after the last IMP dose (morning dose) of the 1st treatment cycle].

- Plasma levels of 2156Y (acidic form of ladarixin) and relevant
metabolites (DF2108Y, S-isomer; DF2227Y, R-isomer) in the whole population [Time frame: within 96 hours after the last IMP dose in at least 2 treatment cycles].

E.3

Principal inclusion criteria

Consented male and female patients aged 14-45 years, inclusive, with
recent onset T1D (randomization scheduled to allow the administration
of the study medication to start within 180 days from 1st insulin
administration). Patients must be positive for at least one diabetesrelated auto-antibody (anti-GAD; IAA, if obtained within 10 days of the
onset of insulin therapy; IA-2 antibody; ZnT8); must require, or have
required insulin delivered via one or more separate subcutaneous
injections or Continuous Subcutaneous Insulin Infusion (CSII); must
have a fasting C-peptide below 0.205 nmol/L, but must retain a Beta-cell
function as per peak stimulated (MMTT) C-peptide level >0.2 nmol/L.

E.4

Principal exclusion criteria

Patients will be excluded if they have a type 2 diabetes or any other
unstable chronic disease for which dose adjustment of specific
medication is anticipated during the trial; moderate to severe renal
impairment calculated by estimated Glomerular Filtration Rate (eGFR)
<60 mL/min/1.73 m2 as determined using Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) creatinine equation; hepatic
dysfunction (increased ALT/AST >3 x upper limit of normal and
increased total bilirubin >3 mg/dL [>51.3 μmol/L]); hypoalbuminemia (serum albumin <3 g/dL); a QTcF > 470 msec.; a history of significant
cardiovascular disease/abnormality; occurrence of an episode of
ketoacidosis or hypoglycemic coma in the past 2 weeks; a known
hypersensitivity to non-steroidal anti-inflammatory drugs. Patients on
treatment with drugs metabolized by CYP2C9 with a narrow therapeutic
index [i.e. phenytoin, warfarin, sulphanylurea hypoglycemics and high
dose of amitriptyline (>50 mg/day)]; patients with past (within 2 weeks
prior to randomization) or current use of antidiabetic agents as
metformin, sulfonylureas, glinides, thiazolidinediones, exenatide,
liraglutide, DPP-IV inhibitors, SGLT-2 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.) will also be excluded. Patients
will be excluded as well in case of past (within 1 month prior to
randomization) or current administration of any immunosuppressive
medications (including oral or systemic corticosteroids) and use of any
investigational agents, including any agents that impact the immune
response or the cytokine system. Additional exclusion criteria will be:
significant systemic infection during the 4 weeks before the 1st dose of
study drug (e.g., infection requiring hospitalization, major surgery, or
i.v. 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); History of positive status
for hepatitis A (IgM), hepatitis B (not due to immunization), hepatitis C
and HIV. Also, pregnant or breastfeeding women or patients unwilling to
use effective contraceptive measures (females and males) will be
excluded.

E.5 End points

E.5.1

Primary end point(s)

- Change from baseline in 2-hour AUC of C-peptide response to the MMTT [Primary endpoint. Time frame: Month 6].

E.5.1.1

Timepoint(s) of evaluation of this end point

At month 6; Month 6 = Week 26 +/- 2 weeks

E.5.2

Secondary end point(s)

- Change from baseline in 2-hour AUC of C-peptide response to the MMTT [Time frame: month 12, 18 and 24].
- Change in HbA1c from baseline [Time frame: Month 6, 12 and 24]
- Time in range (TIR) by Continuous Glucose Monitoring (CGM) [Time frame: Month 6, 12, 18, 24]
- Proportion of patients with HbA1c <7% who did not experience severe hypoglycemic events during treatment [Time frame: Month 6, 12, 18 and 24].
- Average (previous 3 days) daily insulin requirement (IU/kg/day) [Time frame: Month 6, 12, 18 and 24].
- Proportion of patients with HbA1c <7% and daily insulin requirement <0.5 (IU/kg/day)
- Additional Glucose Variability Indices derived from CGM (glucose AUC outside the target range of 70 – 180 mg/dL, 2-hour postprandial glucose (PPG), Mean Amplitude Glycemic Excursions (MAGE), continuous overall net glycemic action (CONGA)-n, Mean Of the Daily Differences (MODD), and mean daily blood glucose, SD (Standard Deviation). [Time frame: Month 6, 12, 18 and 24].
- Number of self-reported episodes of severe hypoglycemia [Time frame: Month 6, 12, 18 and 24].
- Percentage of patients not requiring insulin therapy {Time frame: Month 6, 12, 18 and 24]
- Estimated Glucose Disposal Rate (eGDR) [Time frame: Month 6, 12, 18 and 24].

E.5.2.1

Timepoint(s) of evaluation of this end point

Month 6 = Week 26+2; Month 12 = Week 52+2; Month 18 = Week 78+2; Month 24 = Week 104+2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Georgia

Israel

Serbia

United States

Belgium

Germany

Italy

Slovenia

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

For the purpose of this trial, the End of Study is defined as the date of the last visit of the last patient.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

112

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

140

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After completion of the week 104 (month 24) follow-up visit, patients will receive post-study care as prescribed by their health care provider. No post-study treatment will be provided by Dompé.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-12-08

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status

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