PIONEER TEENS. A research study to compare a new medicine oral semaglutide to a dummy medicine in children and teenagers with type 2 diabetes.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

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

Trial duration

30 Oct 2020 → 30 Apr 2026

Decision date (initial)

2024-06-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2023-506923-27-00

EudraCT number

2018-002952-34

WHO UTN

U1111-1218-1527

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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.

Secondary objectives 2

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 parameters of body composition
2. To asses 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.

Conditions and MedDRA coding

Type 2 diabetes

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001441-PIP02-15

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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.
2. Male or female, aged 10 to <18 years at the day of randomisation.
3. HbA1c 6.5%−11.0% (47−97 mmol/mol) (both inclusive)
4. 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

Exclusion criteria 3

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline (week 0) to week 26 in glycosylated haemoglobin (HbA1c) (%-point and mmol/mol)

Secondary endpoints 50

1. Change from baseline (week 0) to week 26 in fasting plasma glucose (FPG) (mmol/L)
2. Change from baseline (week 0) to week 26 in body mass index (BMI) standard deviation score (SDS)
3. Change from baseline (week 0) to week 26 and to week 52 in HbA1c (%-point and mmol/mol) (only at week 52)
4. Change from baseline (week 0) to week 26 and to week 52 in FPG (mmol/L) (only at week 52)
5. Change from baseline (week 0) to week 26 and to week 52 in body weight (kg)
6. Change from baseline (week 0) to week 26 and to week 52 in body weight (relative change, %)
7. Change from baseline (week 0) to week 26 and to week 52 in waist circumference (cm)
8. Change from baseline (week 0) to week 26 and to week 52 in BMI SDS (only at week 52)
9. Change from baseline (week 0) to week 26 and to week 52 in BMI percentile (age and gender adjusted) (%)
10. Change from baseline (week 0) to week 26 and to week 52 in systolic and diastolic blood pressure (mmHg)
11. HbA1c <7.0% (53 mmol/mol) at week 26 (yes/no), American Diabetes Association (ADA) target and International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines from 201818
12. HbA1c ≤6.5% (48 mmol/mol) at week 26 (yes/no), American Association of Clinical Endocrinologists (AACE) target
13. HbA1c <7.0% (53 mmol/mol) at week 52 (yes/no), ADA target and ISPAD guidelines from 201818
14. HbA1c ≤6.5% (48 mmol/mol) at week 52 (yes/no), AACE target
15. Time to additional anti-diabetic medication (to support the treatment policy estimand)
16. Time to rescue medication (to support the hypothetical estimand)
17. Number of treatment-emergent adverse events (TEAEs) during exposure to trial product, assessed up to approximately 57 weeks
18. Number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes from randomisation to week 26
19. Number of treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes during exposure to trial product, assessed up to approximately 57 weeks
20. Treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemia episode from randomisation to week 26 (yes/no)
21. Treatment-emergent severe or blood glucose confirmed symptomatic hypoglycaemia episode during exposure to trial product, assessed up to approximately 57 weeks (yes/no)
22. Change from baseline (week 0) to week 26 and week 52 in biochemistry
23. Change from baseline (week 0) to week 26 and week 52 in amylase (U/L)
24. Change from baseline (week 0) to week 26 and week 52 in lipase (U/L)
25. Change from baseline (week 0) to week 26 and week 52 in biomarkers
26. Change from baseline (week 0) to week 26 and week 52 in insulin-like growth factor 1 (IGF-1) (ng/mL)
27. Change from baseline (week 0) to week 26 and week 52 in insulin–like growth factor binding protein 3 (IGFBP 3) (ng/mL)
28. Change from baseline (week 0) to week 26 and week 52 in hormones
29. Change from baseline (week 0) to week 26 and week 52 in calcitonin (pmol/L)
30. Change from baseline (week 0) to week 26 and week 52 in estradiol (for girls) (pmol/L)
31. Change from baseline (week 0) to week 26 and week 52 in testosterone (for boys) (nmol/L)
32. Change from baseline (week 0) to week 26 and week 52 in prolactin (mIU/L)
33. Change from baseline (week 0) to week 26 and week 52 in thyroid stimulating hormone (TSH/thyrotropin) (mIU/L)
34. Change from baseline (week 0) to week 26 and week 52 in follicle stimulating hormone (FSH) (mIU/mL)
35. Change from baseline (week 0) to week 26 and week 52 in luteinizing hormone (LH) (mIU/mL)
36. Change from baseline (week 0) to week 26 and week 52 in dehydroepiandrosterone sulfate (DHEAS) (μmol/L)
37. Anti-semaglutide antibodies endpoints during 57 weeks - anti-semaglutide antibody status.
38. Anti-semaglutide antibodies endpoints during 57 weeks - Anti-semaglutide antibody titer.
39. Anti-semaglutide antibodies endpoints during 57 weeks - Anti-semaglutide antibodies with in vitro neutralising effect to semaglutide
40. Anti-semaglutide antibodies endpoints during 57 weeks - Anti-semaglutide antibodies cross reacting with endogenous GLP-1
41. Anti-semaglutide antibodies endpoints during 57 weeks - Cross reacting antibodies with in vitro neutralising effect to endogenous GLP-1
42. The following will be assessed at week 26 and week 52 - Height velocity (cm/year)
43. The safety assessments are change from baseline (week 0) to week 26 and week 52 in - Height SDS
44. The safety assessments are change from baseline (week 0) to week 26 and week 52 in - Bone age assessment, X-ray (only at week 52) (years)
45. The safety assessments are change from baseline (week 0) to week 26 and week 52 in - Pubertal assessment (Tanner staging) (stage 1-5 where 5 is full sexual maturity)
46. The safety assessments are change from baseline (week 0) to week 26 and week 52 in - Pulse rate (beats/minute)
47. Change from pre-dose to post-dose (25 and 40 min) at week 12 and week 26 in Lactate (mmol/L)
48. Pharmacokinetic (PK) sampling of semaglutide from eight visits over the treatment period of 52 weeks with three samples performed during the dose escalation period will be included in an analysis comparing the following PK properties to historical adult data, at steady state - Apparent clearance (CL/F) (L/h)
49. Pharmacokinetic (PK) sampling of semaglutide from eight visits over the treatment period of 52 weeks with three samples performed during the dose escalation period will be included in an analysis comparing the following PK properties to historical adult data, at steady state -Average concentration (Cavg) (nmol/L)
50. SNAC PK samples collected in this trial will be evaluated using relevant summary statistics and compared to historical adult data - SNAC plasma concentrations (ng/mL)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 8

Locations

6 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 138 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications