Clinical Trials Register

Summary
EudraCT Number:	2020-002374-27
Sponsor's Protocol Code Number:	NN1436-4625
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-08
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

2020-002374-27

A.3

Full title of the trial

Efficacy and safety of once weekly insulin icodec compared to once daily
insulin degludec 100 units/mL, both in combination with insulin aspart, in
adults with type 1 diabetes.
A 26-week, randomised, multicentre, open-label, active-controlled, parallel
group, two armed, treat-to-target trial investigating the effect on
glycaemic control and safety of treatment with once weekly insulin icodec
compared to once daily insulin degludec, both in combination with insulin
aspart in adults with type 1 diabetes, with a 26-week extension
investigating long term safety.

Studio clinico per confrontare l’Efficacia e la sicurezza dell’insulina settimanale icodec una volta alla settimana rispetto all’insulina giornaliera degludec 100 unità/ml una volta al giorno, entrambe in combinazione con insulina aspart, in adulti con diabete di tipo 1.
Studio clinico di 26 settimane, treat-to-target, randomizzato, multicentrico, in aperto, con controllo attivo, a gruppi paralleli, a due bracci, per valutare l’effetto sul controllo glicemico e sulla sicurezza del trattamento con insulina settimanale icodec rispetto a insulina giornaliera degludec, entrambe in combinazione con insulina aspart in adulti con diabete di tipo 1, con una fase di estensione di 26 settimane per valutare la sicurezza a lungo termine.

A.3.1

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

A research study to compare a new weekly insulin, insulin icodec, and an
available daily insulin, insulin degludec, both in combination with mealtime
insulin in people with type 1 diabetes

Studio clinico di confronto tra due tipi di insuline, una nuova a somministrazione settimanale (insulina icodec) ed una nota a somministrazione giornaliera (insulina degludec), entrambe in combinazione con insulina da assumere ai pasti, in persone con diabete di tipo 1.

A.3.2

Name or abbreviated title of the trial where available

ONWARDS 6

A.4.1

Sponsor's protocol code number

NN1436-4625

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1251-7315

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	NOVO NORDISK. 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	Novo Nordisk A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novo Nordisk A/S
B.5.2	Functional name of contact point	Clinical Transparency (1452)
B.5.3	Address:
B.5.3.1	Street Address	Novo Allé
B.5.3.2	Town/ city	Bagsværd
B.5.3.3	Post code	2880
B.5.3.4	Country	Denmark
B.5.6	E-mail	clinicaltrials@novonordisk.com

D. IMP Identification
D.IMP: 1
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	Tresiba 100 units/mL solution for injection in pre-filled pen
D.2.1.1.2	Name of the Marketing Authorisation holder	Novo Nordisk A/S
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.3.1	Product name	N/A
D.3.2	Product code	[N/A]
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	insulin degludec
D.3.9.1	CAS number	844439-96-9
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	INSULIN DEGLUDEC
D.3.9.4	EV Substance Code	SUB96394
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	100
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	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	insulin icodec 700 U/mL PDS290
D.3.2	Product code	[.]
D.3.4	Pharmaceutical form	Suspension 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
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	INSULIN 287
D.3.9.4	EV Substance Code	SUB50453
D.3.10	Strength
D.3.10.1	Concentration unit	nmol/ml nanomole(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4200
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

Diabetes Mellitus, Type 1

Diabete Mellito di Tipo 1

E.1.1.1

Medical condition in easily understood language

Type 1 diabetes

Diabete Tipo 1

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	LLT
E.1.2	Classification code	10045228
E.1.2	Term	Type I diabetes mellitus
E.1.2	System Organ Class	100000004861

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 confirm the effect on glycaemic control of once weekly insulin icodec in combination with insulin aspart, in subjects with T1D. This includes comparing the difference in change from baseline in HbA1c between
once weekly insulin icodec and once daily insulin degludec both in combination with insulin aspart after 26 weeks of treatment to a noninferiority limit of 0.3%.

Confermare l'effetto sul controllo glicemico dell'insulina icodec una volta alla settimana in combinazione con insulina aspart, in soggetti con T1D. Ciò comprende confrontare la differenza nella variazione dell'HbA1c basale tra insulina icodec una volta alla settimana e insulina degludec una volta al giorno entrambe in combinazione con insulina aspart dopo 26 settimane di trattamento a una non inferiorità limite dello 0,3%.

E.2.2

Secondary objectives of the trial

To compare the safety and patient reported outcomes of once weekly insulin icodec versus once daily insulin degludec, both in combination with insulin aspart, in subjects with T1D.

Confrontare la sicurezza e i risultati riportati dal paziente che assume insulina icodec settimanale rispetto all'insulina degludec giornaliera, entrambe in combinazione con insulina aspart, nei soggetti con T1D.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or female aged 18 years or more at the time of signing informed consent.
- Diagnosed with type 1 diabetes mellitus at least 1 year prior to the day of screening.
- Treated with multiple daily insulin injections (basal and bolus insulin analogue regimes) at least 1 year prior to the day of screening.
- HbA1c below 10% at screening visit based on analysis from central laboratory.

- Uomo o donna di età pari o superiore a 18 anni al momento della firma del consenso informato.
- Diagnosi di diabete mellito di tipo 1 almeno 1 anno prima del giorno dello screening.
- Trattato con iniezioni multiple giornaliere di insulina (regimi analoghi di insulina basale e bolo) almeno 1 anno prima del giorno dello screening.
- HbA1c inferiore al 10% alla visita di screening sulla base dell'analisi del laboratorio centrale.

E.4

Principal exclusion criteria

- Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
- Chronic heart failure classified as New York Heart Association (NYHA) Class IV at screening.
- Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

- Infarto del miocardio, ictus, ospedalizzazione per angina pectoris instabile o attacco ischemico transitorio nei 180 giorni precedenti il ¿¿giorno dello screening.
- Insufficienza cardiaca cronica classificata come Classe IV della New York Heart Association (NYHA) allo screening.
- Inizio o modifica anticipata di farmaci concomitanti (per più di 14 giorni consecutivi) noti per influenzare il peso o il metabolismo del glucosio (ad es. Trattamento con orlistat, ormoni tiroidei o corticosteroidi).
- Retinopatia o maculopatia diabetica non controllata e potenzialmente instabile. Verificato da un esame del fondo oculare eseguito negli ultimi 90 giorni prima dello screening o nel periodo tra lo screening e la randomizzazione. La dilatazione farmacologica della pupilla è un requisito a meno che non si utilizzi una fotocamera digitale per la fotografia del fondo oculare specificata per l'esame non dilatato.

E.5 End points

E.5.1

Primary end point(s)

1. Change in HbA1c

1. Cambiamento dell'HbA1c

E.5.1.1

Timepoint(s) of evaluation of this end point

1. From baseline (week 0) to week 26

1. Dal basale (settimana 0) alla settimana 26

E.5.2

Secondary end point(s)

1. Change in fasting plasma glucose (FPG)
2. Time in range 3.9-10.0 mmol/L (70-180 mg/dL) *using continuous glucose monitoring (CGM) system, Dexcom G6
3. Change in DTSQs (DiabetesTreatment Satisfaction Questionnaire) in total treatment satisfaction
4. Change in HbA1c
5. Number of severe hypoglycaemic episodes (level 3)
6. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter)
7. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)
8. Number of severe hypoglycaemic episodes (level 3)
9. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter)
10. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)
11. Number of nocturnal clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)
12. Number of nocturnal clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)
13. Time spent < 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6
14. Time spent > 10 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6
15. Mean total weekly insulin dose
16. Mean total weekly insulin dose
17. Change in body weight

1. Variazione della glicemia a digiuno (FPG)
2. Tempo nell'intervallo 3,9-10,0 mmol / L (70-180 mg / dL) * utilizzando la modalità del sistema di monitoraggio continuo del glucosio (CGM), Dexcom G6
3. Variazione dei DTSQ (Questionario sulla soddisfazione del trattamento del diabete) nella soddisfazione al trattamento totale
4. Variazione di HbA1c
5. Numero di episodi ipoglicemici gravi (livello 3)
6. Numero di episodi ipoglicemici clinicamente significativi (livello 2) (<3,0 mmol / L (54 mg / dL), confermato dal glucometro)
7. Numero di episodi ipoglicemici clinicamente significativi (livello 2) (<3,0 mmol / L (54 mg / dL), confermato dal glucometro) o grave episodi ipoglicemici (livello 3)
8. Numero di episodi ipoglicemici gravi (livello 3)
9. Numero di episodi ipoglicemici clinicamente significativi (livello 2) (<3,0 mmol / L (54 mg / dL), confermato dal glucometro)
10. Numero di episodi ipoglicemici clinicamente significativi (livello 2) (<3,0 mmol / L (54 mg / dL), confermato dal glucometro) o episodi ipoglicemici gravi (livello 3)
11. Numero di episodi ipoglicemici notturni clinicamente significativi (livello 2) (<3,0 mmol / L (54 mg / dL), confermato dal glucometro) o episodi ipoglicemici gravi (livello 3)
12. Numero di episodi ipoglicemici notturni clinicamente significativi (livello 2) (<3,0 mmol / L (54 mg / dL), confermato dal glucometro) o episodi ipoglicemici gravi (livello 3)
13. Tempo trascorso <3,0 mmol / L (54 mg / dL) utilizzando il sistema di monitoraggio continuo del glucosio (CGM), Dexcom G6
14. Tempo trascorso> 10 mmol / L (180 mg / dL) utilizzando sistema di monitoraggio continuo del glucosio (CGM), Dexcom G6
15. Dose media settimanale totale di insulina
16. Dose media settimanale totale di insulina
17. Variazione del peso corporeo

E.5.2.1

Timepoint(s) of evaluation of this end point

1., 3., 5.-7., 11. and 17. From baseline (week 0) to week 26
2. From week 22 to week 26
4. From baseline (week 0) to week 52
8.-10. and 12. From baseline (week 0) to week 57
13.-14. From week 22 to week 26
15. From week 24 to week 26
16. From week 50 to week 52

1., 3., 5.-7., 11. e 17. Dal basale (settimana 0) alla settimana 26
2. Dalla settimana 22 alla settimana 26
4. Dal basale (settimana 0) alla settimana 52
8.-10. e 12. Dal basale (settimana 0) alla settimana 57
13.-14. Dalla settimana 22 alla settimana 26
15. Dalla settimana 24 alla settimana 26
16. Dalla settimana 50 alla settimana 52

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)

Yes

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

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

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

Canada

India

Japan

Russian Federation

Turkey

United States

European Union

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

LVLS, Last Visit Last Subject, ultima visita dell'ultimo paziente

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:

552

F.1.3

Elderly (>=65 years)

Yes

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

160

F.4.2.2

In the whole clinical trial

580

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

2021-04-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-18

P. End of Trial
P.	End of Trial Status	Ongoing

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IMP with orphan designation in the indication
Orphan Designation Number:
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