STEP Young: A research study on how well semaglutide helps children and teenagers with excess body weight lose weight

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

3 Jul 2023 → ongoing

Decision date (initial)

2023-06-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2022-502922-41-00

WHO UTN

U1111-1266-3808

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others

Group Kids: To confirm superiority of semaglutide s.c. once-weekly versus placebo as an adjunct to a reduced-calorie diet and increased physical activity on weight management in children with obesity (ages 6 to <12 years).

Secondary objectives 4

1. Group Kids: To confirm superiority of semaglutide s.c. once-weekly versus placebo as an adjunct to a reduced-calorie diet and increased physical activity with respect to achieving improvement in body weight category after 68 weeks in children with obesity (ages 6 to <12 years).
2. Group Kids: To compare the effect of semaglutide s.c. once-weekly versus placebo as an adjunct to a reduced-calorie diet and increased physical activity in children with obesity (ages 6 to <12 years) on: Weight-related parameters, Cardiovascular risk factors, Glucose metabolism, Body composition (for subpopulation having DXA scan)
3. Group Teens: To compare the effect of semaglutide s.c. once-weekly versus placebo as an adjunct to a reduced-calorie diet and increased physical activity in adolescents with obesity, or overweight with ≥ 1 weight-related comorbidity, (ages 12 to <18 years) on: Weight-related parameters, Cardiovascular risk factors, Glucose metabolism, Body composition (DXA scan)
4. To compare the safety and tolerability of semaglutide s.c. once-weekly versus placebo as an adjunct to a reduced-calorie diet and increased physical activity in children with obesity (ages 6 to <12 years), adolescents with obesity, or overweight with ≥ 1 weight-related comorbidity (ages 12 to <18 years) (Note - The groups will be analysed separately)

Conditions and MedDRA coding

Obesity and overweight

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001441-PIP03-17

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Informed consent of parent(s) or legally acceptable representative (LAR) of participant and child assent, obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study. a. The parent(s) or LAR of the child must sign and date the Informed Consent Form (according to local requirements) b. The child must sign and date the Child Assent Form or provide oral assent (according to local requirements)
2. Age, at the time of signing informed consent, of: a. Group Kids: 6 to < 12 years, b. Group Teens: 12 to < 18 years, and Tanner stage > 1
3. BMI, at screening and randomisation, corresponding to a. Group Kids: ≥95th percentile, b. Group Teens: ≥95th percentile or ≥85th percentilea with the presence of at least 1 weight-related comorbidity (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or T2D
4. History of at least one unsuccessful effort to lose sufficient body weight after participation in a structured lifestyle modification programme (diet and exercise counselling) for at least 3 months (As declared by the participant (or by parent(s)/LAR where applicable) or reported in the participant’s medical records)
5. Body weight of >45 kg at screening and randomisation.
6. [For participants with T2D at screening the following inclusion criteria apply in addition to criteria 1-5:] Treatment with either lifestyle intervention, or treatment with metformin according to local label. Treatment with metformin should be stable (same drug(s), dose, and dosing frequency) for at least 90 days before screening
7. [For participants with T2D at screening the following inclusion criteria apply in addition to criteria 1-5:] HbA1c ≤10.0% (86 mmol/mol) as measured by central laboratory at screening
8. [For participants assessed by DXA scan the following additional criteria must apply]: Evaluation of the quality of the DXA scan must be performed and found acceptable by the imaging laboratory prior to randomisation
9. [For participants assessed by DXA scan the following additional criteria must apply]: BMI ≤ 40.0 kg/m2 at screening

Exclusion criteria 32

1. [Obesity related] Treatment with any medication prescribed for the indication of obesity or weight management within 90 days before screening
2. [Obesity related] Previous or planned (during the study period) obesity treatment with surgery or a weight loss device. However, the following are allowed: (1) liposuction and/or abdominoplasty, if performed >1 year prior to screening, (2) adjustable gastric banding, if the band has been removed >1 year prior to screening, (3) intragastric balloon, if the balloon has been removed >1 year prior to screening or (4) duodenal-jejunal bypass liner (e.g., Endobarrier), if the sleeve has been removed >1 year prior to screening.
3. [Obesity related] Uncontrolled thyroid disease
4. [Obesity related] Participants with endocrine, hypothalamic, or syndromic obesity
5. [Obesity related] A self-reported (or by parent(s)/LAR where applicable) change in body weight >5% within 90 days before screening irrespective of medical record
6. [Mental health] History of major depressive disorder within 2 years before screening (As declared by the participant (or by parent(s)/LAR where applicable) or reported in the participant’s medical records)
7. [Mental health] Diagnosis of other severe psychiatric disorders (e.g., schizophrenia, bipolar disorder) [As declared by the participant (or by parent(s)/LAR where applicable) or reported in the participant’s medical records]
8. [Mental health] A lifetime history of suicidal attempt (As declared by the participant (or by parent(s)/LAR where applicable) or reported in the participant’s medical records)
9. [Mental health] Suicidal behaviour within 30 days before screening (As declared by the participant (or by parent(s)/LAR where applicable) or reported in the participant’s medical records)
10. [Additional mental health for Group Teens] A Patient Health Questionnaire-9 (PHQ-9) score of ≥15 at screening
11. [Additional mental health for Group Teens] Suicidal ideation corresponding to type 4 or 5 based on the Columbia-Suicide Severity Rating Scale (C-SSRS) within 30 days before screening
12. [General Safety] History or presence of chronic pancreatitis (As declared by the participant (or by parent(s)/LAR where applicable) or reported in the participant’s medical records)
13. [General Safety] Presence of acute pancreatitis within 180 days before screening (As declared by the participant (or by parent(s)/LAR where applicable) or reported in the participant’s medical records)
14. [General Safety] Calcitonin ≥50 ng/L
15. [General Safety] Personal, or first-degree relative’s, history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma (As declared by the participant (or by parent(s)/LAR where applicable) or reported in the participant’s medical records)
16. [General Safety] Type 1 diabetes mellitus or monogenic diabetes
17. [General Safety] Renal impairment with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, as calculated by the Bedside Schwartz equation (According to the current version of National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, National Institutes of Health) and Kidney Disease Improving Global Outcomes (KDIGO) pediatric clinical practice guidelines)
18. [General Safety] Presence or history of malignant neoplasms within the past 5 years prior to the day of screening (As declared by the participant (or by parent(s)/LAR where applicable) or reported in the participant’s medical records)
19. [General Safety] Surgery scheduled for the duration of the study, except for minor surgical procedures, in the opinion of the investigator
20. [General Safety] Known or suspected abuse of alcohol or recreational drugs
21. [General Safety] Use of any medication with unknown or unspecified content within 90 days before screening
22. [General Safety] Known or suspected hypersensitivity to study product(s) or related products
23. [General Safety] Previous participation in this study. Participation is defined as signed informed consent
24. [General Safety] Participation (i.e., signed informed consent) in any interventional, clinical study of an approved or non-approved investigational medicinal product within 90 days before screening
25. [General Safety] Other participant(s) from the same household participating in any semaglutide study
26. [General Safety] Known history of heart disease (including history of clinically significant arrhythmias or conduction delays on ECG) within 180 days before screening, new clinically significant arrhythmias or conduction delays on ECG identified at screening
27. [General Safety] Female who is pregnant, breast feeding, intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method, as defined in Appendix 4, Section ‎10.4
28. [General Safety] Any disorder, unwillingness, or inability, not covered by any of the other exclusion criteria, which in the investigator’s opinion, might jeopardise the participant’s safety or compliance with the protocol
29. [Glycaemia-related] Treatment with glucose-lowering agent(s) within 90 days before screening (except for metformin)
30. [Glycaemia-related] Treatment with a GLP-1 receptor agonist within 180 days before screening
31. [Diabetes related for participants with T2D] Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before 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
32. [Diabetes related for participants with T2D] 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. [Group Kids] Change in BMI, Baseline (week 0) to week 68

Secondary endpoints 57

1. [Group Kids] [Confirmatory secondary endpoint], Improvement in weight category (Based on CDC sex- and age-specific growth charts), Baseline (week 0) to week 68
2. [Group Kids] [Supportive secondary endpoint] Change in BMI, Week 0 to week 104
3. [Group Kids] [Supportive secondary endpoint] Improvement in weight category (Based on CDC sex- and age-specific growth charts), Week 0 to week 104
4. [Group Kids] [Supportive secondary endpoint] Change in body weight, Week 0 to week 68, Week 0 to week 104
5. [Group Kids] [Supportive secondary endpoint] Change in BMI percentage of the 95th percentile (Based on CDC sex- and age-specific growth charts), Week 0 to week 68, Week 0 to week 104
6. [Group Kids] [Supportive secondary endpoint] Change in BMI, SDS (standard deviation score) [As defined by the WHO BMI-for-age growth reference chart], Week 0 to week 68, Week 0 to week 104
7. [Group Kids] [Supportive secondary endpoint] Change in waist circumference, Week 0 to week 68, Week 0 to week 104
8. [Group Kids] [Supportive secondary endpoint] Change in systolic blood pressure, Week 0 to week 68, Week 0 to week 104
9. [Group Kids] [Supportive secondary endpoint] Change in diastolic blood pressure, Week 0 to week 68, Week 0 to week 104
10. [Group Kids] [Supportive secondary endpoint] Change in total cholesterol, Week 0 to week 68, Week 0 to week 104
11. [Group Kids] [Supportive secondary endpoint] Change in HDL, Week 0 to week 68, Week 0 to week 104
12. [Group Kids] [Supportive secondary endpoint] Change in LDL, Week 0 to week 68, Week 0 to week 104
13. [Group Kids] [Supportive secondary endpoint] Change in VLDL, Week 0 to week 68, Week 0 to week 104
14. [Group Kids] [Supportive secondary endpoint] Change in triglycerides, Week 0 to week 68, Week 0 to week 104
15. [Group Kids] [Supportive secondary endpoint] Change in hs-CRP, Week 0 to week 68, Week 0 to week 104
16. [Group Kids] [Supportive secondary endpoint] Change in HbA1c, Week 0 to week 68, Week 0 to week 104
17. [Group Kids] [Supportive secondary endpoint] Change in fasting plasma glucose, Week 0 to week 68, Week 0 to week 104
18. [Group Kids] [Supportive secondary endpoint] Change in fasting insulin, Week 0 to week 68, Week 0 to week 104
19. Change in ALT, Week 0 to week 68, Week 0 to week 104
20. [Group Kids] [Supportive secondary endpoint] Change in total fat mass, by DXA (For the population who have DXA scans) relative to total body mass, Week 0 to week 68, Week 0 to week 104
21. [Group Kids] [Supportive secondary endpoint] Change in lean body mass, by DXA (For the population who have DXA scans) relative to total body mass, Week 0 to week 68, Week 0 to week 104
22. [Group Kids] [Supportive secondary endpoint] Relative change in visceral fat mass by DXA (For the population who have DXA scans), Week 0 to week 68, Week 0 to week 104
23. [Group Kids] [Supportive secondary endpoint] Participants achieving ≥5% reduction of BMI (yes/no), Week 0 to week 68, Week 0 to week 104
24. [Group Kids] [Supportive secondary endpoint] Participants achieving ≥10% reduction of BMI (yes/no), Week 0 to week 68, Week 0 to week 104
25. Participants achieving ≥15% reduction of BMI (yes/no), Week 0 to week 68, Week 0 to week 104
26. [Group Teens] [Supportive secondary endpoint] Change in BMI, Week 0 to week 68, Week 0 to week 104
27. [Group Teens] [Supportive secondary endpoint] Improvement in weight category (Based on CDC sex- and age-specific growth charts), Week 0 to week 68, Week 0 to week 104
28. [Group Teens] [Supportive secondary endpoint] Change in body weight, Week 0 to week 68, Week 0 to week 104
29. [Group Teens] [Supportive secondary endpoint] Change in BMI percentage of the 95th percentile (Based on CDC sex- and age-specific growth charts), Week 0 to week 68, Week 0 to week 104
30. [Group Teens] [Supportive secondary endpoint] Change in BMI, SDS (standard deviation score) [As defined by the WHO BMI-for-age growth reference chart], Week 0 to week 68, Week 0 to week 104
31. [Group Teens] [Supportive secondary endpoint] Change in waist circumference, Week 0 to week 68, Week 0 to week 104
32. [Group Teens] [Supportive secondary endpoint] Change in systolic blood pressure, Week 0 to week 68, Week 0 to week 104
33. [Group Teens] [Supportive secondary endpoint] Change in diastolic blood pressure, Week 0 to week 68, Week 0 to week 104
34. [Group Teens] [Supportive secondary endpoint] Change in total cholesterol, Week 0 to week 68, Week 0 to week 104
35. [Group Teens] [Supportive secondary endpoint] Change in HDL, Week 0 to week 68, Week 0 to week 104
36. [Group Teens] [Supportive secondary endpoint] Change in LDL, Week 0 to week 68, Week 0 to week 104
37. [Group Teens] [Supportive secondary endpoint] Change in VLDL, Week 0 to week 68, Week 0 to week 104
38. [Group Teens] [Supportive secondary endpoint] Change in triglycerides, Week 0 to week 68, Week 0 to week 104
39. [Group Teens] [Supportive secondary endpoint] Change in hs-CRP, Week 0 to week 68, Week 0 to week 104
40. [Group Teens] [Supportive secondary endpoint] Change in HbA1c, Week 0 to week 68, Week 0 to week 104
41. [Group Teens] [Supportive secondary endpoint] Change in fasting plasma glucose, Week 0 to week 68, Week 0 to week 104
42. [Group Teens] [Supportive secondary endpoint] Change in fasting insulin, Week 0 to week 68, Week 0 to week 104
43. [Group Teens] [Supportive secondary endpoint] Change in ALT, Week 0 to week 68, Week 0 to week 104
44. [Group Teens] [Supportive secondary endpoint] Change in total fat mass, by DXA (For the population who have DXA scans) relative to total body mass, Week 0 to week 68, Week 0 to week 104
45. Change in lean body mass, by DXA (For the population who have DXA scans) relative to total body mass, Week 0 to week 68, Week 0 to week 104
46. [Group Teens] [Supportive secondary endpoint] Relative change in visceral fat mass by DXA (For the population who have DXA scans), Week 0 to week 68, Week 0 to week 104
47. [Group Teens] [Supportive secondary endpoint] Participants achieving ≥5% reduction of BMI (yes/no), Week 0 to week 68, Week 0 to week 104
48. [Group Teens] [Supportive secondary endpoint] Participants achieving ≥10% reduction of BMI (yes/no), Week 0 to week 68, Week 0 to week 104
49. [Group Teens] [Supportive secondary endpoint] Participants achieving ≥15% reduction of BMI (yes/no), Week 0 to week 68, Week 0 to week 104
50. Treatment emergent AEs, Week 0 to week 68, Week 0 to week 111
51. Treatment emergent SAEs, Week 0 to week 68, Week 0 to week 111
52. Change in pulse Week 0 to week 68, Week 0 to week 104
53. Change in amylase, Week 0 to week 68, Week 0 to week 104
54. Change in lipase, Week 0 to week 68, Week 0 to week 104
55. Change in calcitonin, Week 0 to week 68, Week 0 to week 104
56. Change in bone mineral density, by DXA (For the population who have DXA scans)
57. Treatment emergent hypoglycaemic episodes (for T2D only) [As defined by ISPAD]

Investigational products

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

Test 6

Placebo 2

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 6

Locations

6 EU/EEA countries · 18 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 91 files

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

Application history

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