Clinical Trials Register

Summary
EudraCT Number:	2018-002952-34
Sponsor's Protocol Code Number:	NN9924-4437
National Competent Authority:	Romania - National Agency for Medicines and Medical Devices
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2024-10-18
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

Romania - National Agency for Medicines and Medical Devices

A.2

EudraCT number

2018-002952-34

A.3

Full title of the trial

Efficacy and safety of oral semaglutide versus placebo both in combination with metformin and/or basal insulin in children and adolescents with type 2 diabetes

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 medicine oral semaglutide to a dummy medicine in children and teenagers with type 2 diabetes

A.3.2

Name or abbreviated title of the trial where available

PIONEER TEENS

A.4.1

Sponsor's protocol code number

NN9924-4437

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1218-1527

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/197/2019

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novo Nordisk A/S
B.1.3.4	Country	Denmark
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 Disclosure (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	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	Rybelsus
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.3.4	Pharmaceutical form	Tablet
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	SEMAGLUTIDE
D.3.9.1	CAS number	910463-68-2
D.3.9.4	EV Substance Code	SUB32188
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	3
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	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	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	Yes
D.2.1.1.1	Trade name	Rybelsus
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.3.4	Pharmaceutical form	Tablet
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	SEMAGLUTIDE
D.3.9.1	CAS number	910463-68-2
D.3.9.4	EV Substance Code	SUB32188
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	7
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	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	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: 3
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	Rybelsus
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.3.4	Pharmaceutical form	Tablet
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	SEMAGLUTIDE
D.3.9.1	CAS number	910463-68-2
D.3.9.4	EV Substance Code	SUB32188
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	14
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	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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
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

Diabetes Mellitus, Type 2

E.1.1.1

Medical condition in easily understood language

Type 2 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	LLT
E.1.2	Classification code	10045242
E.1.2	Term	Type II 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 confirm superiority of oral semaglutide at the maximum tolerated dose* (3 mg, 7 mg or 14 mg) versus placebo on glycaemic control in children and adolescents (age 10 to <18 years) with type 2 diabetes on a background treatment of metformin or basal insulin or both.

*maximum tolerated dose is defined as maximum dose level defined according to individual glycaemic response and tolerability as assessed by the investigator

E.2.2

Secondary objectives of the trial

1. To assess and compare the efficacy of oral semaglutide at the maximum tolerated dose (3 mg, 7 mg or 14 mg) versus placebo on a background treatment of metformin or basal insulin or both on:
A. Other parameters of glycaemic control
B. Parameters of body composition
C. Growth parameters
D. Cardio-metabolic parameters
2. To assess and compare the safety and tolerability of oral semaglutide at the maximum tolerated dose (3 mg, 7 mg or 14 mg) versus placebo on a background treatment of metformin or basal insulin or both.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Informed consent from parent(s) or legally acceptable representative (LAR) and child assent from the subject obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
- Male or female, aged 10 to less than18 years at the day of randomisation.
- Glycosylated haemoglobin (HbA1c) 6.5−11.0 percent (47−97 mmol/mol) (both inclusive).
- Diagnosed with type 2 diabetes mellitus according to the American Diabetes Association criteria and treated with:
- stable metformin dose* or
- stable metformin dose* and a stable dose of basal insulin** or
- stable dose of basal insulin**
*stable metformin dose is defined as at least 1000 mg daily or the maximum tolerated dose for 56 days or longer prior to screening.
**stable dose of basal insulin is defined as basal insulin treatment more than or equal to 30 days prior to screening, compared to the dose at screening, dose adjustments of plus or minus 25 percent are allowed.

E.4

Principal exclusion criteria

- Diagnosis of type 1 diabetes.
- Maturity onset diabetes of the young (MODY).
- Positive insulinoma associated-protein 2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies.

E.5 End points

E.5.1

Primary end point(s)

Change in glycosylated haemoglobin (HbA1c) (%-point and mmol/mol)

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline (week 0) to week 26

E.5.2

Secondary end point(s)

1. Change in HbA1c (week 52)
2. Change in fasting plasma glucose (FPG)
3. Change in body mass index (BMI) standard deviation score (SDS)
4. Change in body weight (kg)
5. Change in body weight (relative change in %)
6. Change in waist circumference
7. Change in BMI percentile (age and gender adjusted)
8. Change in systolic and diastolic blood pressure
9. HbA1c <7.0% (53 mmol/mol) (yes/no), American Diabetes Association (ADA) target and International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines from 2018 (week 26)
10. HbA1c ≤6.5% (48 mmol/mol) (yes/no), American Association of Clinical Endocrinologists (AACE) target (week 26)
11. HbA1c <7.0% (53 mmol/mol) (yes/no), ADA target and ISPAD guidelines from 2018 (week 52)
12. HbA1c ≤6.5% (48 mmol/mol) (yes/no), AACE target (week 52)
13. Time to additional anti-diabetic medication
14. Time to rescue medication
15. Number of treatment-emergent adverse events (TEAEs)
16. Number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes (week 0-26)
17. Number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes (week 0-57)
18. Treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episode (yes/no) (week 0-26)
19. Treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episode (yes/no) (week 0-57)
20. Change in biochemistry, amylase
21. Change in biochemistry, lipase
22. Change in biomarker, insulin-like growth factor 1 (IGF-1)
23. Change in biomarker, insulin–like growth factor binding protein 3 (IGFBP 3)
24. Change in hormone, calcitonin
25. Change in hormone, estradiol (for girls)
26. Change in hormone, testosterone (for boys)
27. Change in hormone, prolactin
28. Change in hormone, thyroid stimulating hormone (TSH/thyrotropin)
29. Change in hormone, follicle stimulating hormone (FSH)
30. Change in hormone, luteinizing hormone (LH)
31. Change in hormone, dehydroepiandrosterone sulfate (DHEAS)

32. Anti-semaglutide antibody status.
33. Anti-semaglutide antibody titer.
34. Anti-semaglutide antibodies with in vitro neutralising effect to semaglutide
35. Anti-semaglutide antibodies cross reacting with endogenous GLP-1
36. Cross reacting antibodies with in vitro neutralising effect to endogenous GLP-1

37. Apparent clearance (CL/F)
38. Average concentration (Cavg)
39. Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) plasma concentrations

E.5.2.1

Timepoint(s) of evaluation of this end point

1. From baseline to week 52
2. – 8. From baseline to week 26 and week 52
9. & 10. At week 26
11. & 12. At week 52
13. & 14. Week 0-52
15. Week 0-57
16. Week 0-26
17. Week 0-57
18. At week 26
19. At week 52
20. – 31. From baseline to week 26 and week 52
32. - 36. Week 0-57
37. - 39. Week 0-52

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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

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

Malaysia

New Zealand

North Macedonia

Ukraine

Taiwan

Australia

India

Israel

Lebanon

Mexico

Morocco

Russian Federation

United Kingdom

United States

European Union

E.8.7

Trial has a data monitoring committee

Yes

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

Yes

F.1.1

Number of subjects for this age range:

132

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

119

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

132

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

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

2022-12-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-07-04

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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