Clinical Trials Register

Summary
EudraCT Number:	2015-001831-18
Sponsor's Protocol Code Number:	LPS13931
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-01-21
Trial results	View 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

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-001831-18

A.3

Full title of the trial

A twenty six week, randomized,open-label, 2-armparallel group real world pragmatic trial to assess the clinical and health outcomes benefit of Toujeo compared to standard of care insulin for initiating basel insulin in insulin Naive patients with uncontrolled type 2 diabetes mellitus, with 6 month extension.

Studio pragmatico nel mondo reale della durata di ventisei settimane, randomizzato, in aperto, su 2 gruppi paralleli, per valutare il beneficio in termini di risultati clinici e lo stato di salute ottenuto con l¿utilizzo di Toujeo rispetto al trattamento con insulina basale standard in pazienti insulino Naive che stanno iniziando il trattamento con insulina basale affetti da diabete mellito di tipo 2 non controllato, con estensione di 6 mesi.

A.3.1

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

A "Real World" Trial to determine efficacy and health outcomes of Toujeo compared to "standard of care" basal insulins in insulin naive patients initiating insulin.

Uno Studio pragmatico nel mondo reale per determinare l¿efficacia e i risultati clinici di Toujeo rispetto al trattamento con insulina basale standard in pazienti che iniziano per la prima volta il trattamento con insulina.

A.3.2

Name or abbreviated title of the trial where available

Reach - Control

A.4.1

Sponsor's protocol code number

LPS13931

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	SANOFI-AVENTIS GROUPE
B.1.3.4	Country	France
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	sanofi-aventis Groupe
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SANOFI S.p.A.
B.5.2	Functional name of contact point	Contact point
B.5.3	Address:
B.5.3.1	Street Address	Viale L. Bodio 37/b
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20158
B.5.3.4	Country	Italy
B.5.4	Telephone number	800226343
B.5.5	Fax number	0039 02 39394168
B.5.6	E-mail	informazioni.medicoscientifiche@sanofi.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	Yes
D.2.1.1.1	Trade name	Toujeo
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-Aventis Deutschland GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INSULINA GLARGINE
D.3.9.1	CAS number	160337-95-1
D.3.9.2	Current sponsor code	HOE901-U300
D.3.9.4	EV Substance Code	SUB08196MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	tutte le insuline appartenenti ai gruppi ATC A10AC e A10AE
D.2.1.1.2	Name of the Marketing Authorisation holder	-
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Type 2 Diabetes Mellitus

Diabete Mellito di tipo 2

E.1.1.1

Medical condition in easily understood language

type 2 diabetes mellitus.

diabete mellito di tipo 2.

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	10067585
E.1.2	Term	Type 2 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

To demonstrate non-inferiority of Toujeo versus ¿standard of care¿ basal insulin therapy measured as HbA1c change.

Dimostrare la non inferiorit¿ di Toujeo rispetto alla terapia standard con insulina basale misurata attraverso la variazione della HbA1c dal basale al mese 6.

E.2.2

Secondary objectives of the trial

¿ Superiority of Toujeo versus ¿standard of care¿ basal insulin if non- inferiority is met, measured as HbA1c change.
¿ Patient persistence with assigned basal insulin therapy for the overall period, ie, from beginning to the end of the trial with or without intensification,
¿ Risk of hypoglycemia including the incidence of documented symptomatic or severe hypoglycemic events (as defined by the ADA Workgroup on Hypoglycemia.
¿ Change in HbA1c at month 12.
¿ Change in fasting plasma glucose (FPG)
¿ Change in body weight
¿ Differences in patient reported outcomes measured by Diabetes Treatment Satisfaction Questionnaire Status and Change Versions (DTSQs and DTSQc)
¿ Change in hypoglycemia control subscale (HCS)
¿ Healthcare resource utilization including hospitalizations and emergency department or other health care provider visits and healthcare costs.

¿ Superiorit¿ di Toujeo rispetto alla terapia standard con insulina basale se il criterio di non inferiorit¿, misurato attraverso la variazione della HbA1c dal basale al mese 6, sar¿ stato soddisfatto.
¿ Permanenza del paziente in terapia con insulina basale prescritta per l'intero periodo, vale a dire dall'inizio fino alla fine della sperimentazione con o senza intensificazione.
¿ Rischio di ipoglicemia ivi compresa ipoglicemia sintomatica documentata o grave (secondo il gruppo di lavoro sull¿ ipoglicemia ADA)
¿ Variazione della HbA1c al mese 12.
¿ Variazione della glicemia a digiuno (FPG).
¿ Variazione del peso corporeo.
¿ Differenze nei risultati riferiti dal paziente misurati mediante il Diabetes Treatment Satisfaction Questionnaire, versioni Status e Change (DTSQs e DTSQc).
¿ Variazione della sottoscala di controllo dell'ipoglicemia (HCS).
¿ Utilizzo di Strutt.Sanit.,compresi ricoveri/visite in pronto soccorso, presso altri operatori sanitari e costi dell'assistenza sanitaria

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Patients with type 2 diabetes insufficiently controlled (HbA1c >7%) with current (= 6 months) standard of care with oral agents (metformin, sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT-2 inhibitor, glinide, alphaglucosidase inhibitor), and with or without GLP-1 receptor agonist, and eligible to basal insulin treatment, per investigator’s judgment.
- Adult patients who have signed an informed consent form anda privacy form(s)

- Pazienti con diabete di tipo 2 non sufficientemente controllato (HbA1c >7%) attualmente in terapia (=6 mesi) con farmaci orali (metformina, sulfoniluree, tiazolidinedione, inibitori della DPP-4, inibitori del SGLT-2, glinidi,inibitori delle alfa-glucosidasi) e con o senza l'uso degli agonisti del recettore del GLP-1 e, a giudizio del medico, eleggibili a ricevere il trattamento con insulina.
- Pazienti adulti che hanno firmato il consenso informato

E.4

Principal exclusion criteria

• HbA1c =7%, no upper bound,
• Age <18 years,
• Type 1 diabetes mellitus,
• Any clinically significant abnormality identified on physical examination, laboratory tests, or vital signs at the time of screening, or any major systemic disease resulting in short life expectancy that in the opinion of the Investigator would restrict or limit the patient’s successful participation for the duration of the study,
• Use of any product containing insulin since the time of diagnosis with T2DM other than temporary use during a pregnancy or hospitalization (insulin glargine, Lantus, Levemir, Toujeo Tresiba, Humulin or biosimilar, Humalog , Novolog , Apidra , Afrezza , pre-mix insulin, or other insulin products which become available),
• Use of any product containing insulin occurring within 3 months prior to the time of screening
• Use of oral hypoglycemic agents other than those noted in the inclusion criteria, GLP-1 receptor agonists not approved for use with insulin, or any investigational agent (drug, biologic, device) within 3 months prior to the time of screening.
• All contraindications to commercially available insulin therapy or warnings/precautions of use as displayed in the respective National Product labeling for these products.
• Pregnancy or lactation,
• Women of childbearing potential with no effective contraceptive method
• Hypersensitivity to insulin glargine or Toujeo excipients

· HbA1c =7%, nessun limite superiore.
· Età <18 anni.
· Diabete mellito di tipo 1.
· Qualsiasi alterazione clinicamente significativa identificata in sede di esame obiettivo, test di laboratorio o segni vitali al momento dello screening o qualsiasi importante malattia sistemica risultante in una aspettativa di vita breve che, secondo l'opinione dello sperimentatore, potrebbe restringere o limitare la partecipazione del paziente per tutta la durata dello studio,
· Uso di un qualsiasi prodotto contenente insulina dal momento della diagnosi di T2DM (quali insulina glargine, Lantus, Levemir, Toujeo, Tresiba, Humulin o biosimilare, Humalog®, Novolog®, Apidra®, Afrezza®, insulina premiscelata, o altri prodotti che potrebbero essere disponibili in commercio) eccezion fatta per un uso temporaneo durante la gravidanza o un ricovero,
· Uso di qualsiasi prodotto contenente insulina entro 3 mesi prima dello screening
· Uso di agenti ipoglicemizzanti orali diversi da quelli indicati nei criteri di inclusione, agonisti del recettore del GLP-1 non approvati per l'uso con insulina o qualsiasi prodotto sperimentale (farmaco, biologico, dispositivo) nei 3 mesi precedenti lo screening.
· Tutte le controindicazioni alla terapia con insulina standard disponibile in commercio o le avvertenze/precauzioni d'uso indicate nella relativa etichettatura nazionale di questi prodotti.
· Gravidanza o allattamento
· Donne in età fertile che non utilizzano alcun metodo contraccettivo
· Ipersensibilità all'insulina glargine o agli eccipienti di Toujeo

E.5 End points

E.5.1

Primary end point(s)

Percent change in HbA1c

Variazione % della HbA1c

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to 6 months

dal basale al 6° mese

E.5.2

Secondary end point(s)

Proportion of patient who remain on assigned basal insulin therapy beforem intensification (persistent with assigned therapy); Proportion of patients who remain on assigned basal insulin therapy wheter intensification occured or not; Proportion pf patients who achieve a target HbA1c of(<6,5%, <7%, <7,5%,<8,0%) al mese 6 e al mese 12; Porportion of patients with HbA1c target (threshold listed above; attainment of metabolic benefit) withou documented (BG =70 mg/dL [=3,9 mmol/L]) symptomatic or severe hipoglycemia; Proportion of patients with HbA1c target (thresholds listed above; attainment of metabolic benefit) without documented (BG <54 mg/dl, [3.0 mmol/L]) symptomatic or severe hypoglycemia; Percentage of patients whose HbA1c decreased at least 1%; Percentage of patients whose HbA1c decreased at least 1%; Percentage of patients requiring intensification and time to intensification ; Change in fasting plasma glucose; Percent change in HbA1c

Proporzione di pazienti che continua ad assumere la terapia con insulina basale assegnata prima dell'intensificazione (persistenti alla terapia assegnata) al mese 6 e al mese 12; Proporzione di pazienti che continua ad assumere la terapia con insulina basale, indipendentemente che l'intensificazione sia avvenuta o meno; Proporzione di pazienti che raggiunge il livello target di HbA1c (<6,5%, <7%, <7,5%,<8,0%) al mese 6 e al mese 12; Proporzione di pazienti con HbA1c target (soglie limite summenzionate) (raggiungimento del vantaggio metabolico) al mese 6 e al mese 12 senza ipoglicemia documentata (BG =70 mg/dL [=3,9 mmol/L]) sintomatica o grave ; Proporzione di pazienti con HbA1c target (soglie limite summenzionate) (raggiungimento del vantaggio metabolico) al mese 6 e al mese 12 senza ipoglicemia documentata (BG <54 mg/dl, [3,0 mmol/l]) sintomatica o grave ; Percentuale di pazienti la cui HbA1c ¿ diminuita di almeno l¿ 1% al mese 6 e al mese 12; Percentuale di pazienti la cui HbA1c ¿ diminuita di almeno l¿ 1% al mese 6 e si ¿ mantenuta costante al mese 12; Percentuale di pazienti che necessita di intensificazione al mese 6 e al mese 12, e tempo all'intensificazione; Variazione della glicemia a digiuno dal basale al mese 6 e al mese 12; Variazione della HbA1c (%)

E.5.2.1

Timepoint(s) of evaluation of this end point

at month 6 and month 12; at month 6 and at month 12; at month 6 and month 12; at month 6 and month 12; at month 6 and month 12; at month 6 and month 12; at month 6 and maintained at month 12; at month 6 and month 12; baseline to month 6 and month 12; Baseline to month 12

al mese 6 e al mese 12; al mese e al mese 12; al mese 6 e al mese 12; al mese 6 e al mese 12; al mese 6 e al mese 12; al mese 6 e al mese 12; al mese 6 e mantenuta al mese 12; al mese e al mese 12; dal basale al mese 6 e al mese 12; dal basale al mese 12

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

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

156

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

Information not present in EudraCT

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

Brazil

Mexico

France

Germany

Greece

Ireland

Italy

Romania

Spain

United Kingdom

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

LVLS

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

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

450

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

230

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

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

600

F.4.2.2

In the whole clinical trial

680

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)

NONE

NESSUNO

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

2015-12-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-10-08

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
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