A Research Study on How Well Semaglutide Helps Children and Teenagers With Excess Body Weight Lose Weight

Study Overview
=================
Brief Summary
-----------------
This study will look at how well semaglutide helps children and teenagers losing weight. This will be tested by comparing the effect on body weight in children and teenagers taking semaglutide in comparison to placebo, a dummy medicine. In addition to taking the medicine, the child's parent and the child will have talks with study staff about healthy food choices, how to be more physically active and what your child can do to try to lose weight. The child will either get semaglutide or a dummy medicine. Which treatment the child will get is decided by chance. Semaglutide is an approved medicine for type 2 diabetes and weight management in adults. The child will get one injection once a week. The study medicine is injected with a thin needle in the stomach, thighs or upper arms. The study will last for about 2 ½ years (132 weeks).

Official Title
-----------------
Long-term Safety and Efficacy of Semaglutide s.c. Once-weekly on Weight Management in Children and Adolescents (Aged 6 to <18 Years) With Obesity or Overweight

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Drug: Semaglutide
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Informed consent of parent(s) or legally acceptable representative (LAR) of participant and child assent, as age-appropriate, 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 parents 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) Age at the time of signing informed consent. a)Group Kids: 6 to less than 12 years. b) Group Teens: 12 to less than 18 years and Tanner stage greater than 1 Body mass index (BMI), at screening and randomisation, corresponding to a) Group Kids: greater than or equal to 95th percentile. b) Group Teens: greater than or equal to 95th percentile or greater than or equal to 85th percentile with the presence of at least 1 weight-related comorbidity (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or type 2 diabetes mellitus (T2D) 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 Body weight of greater than 45 kilogram (kg) at screening and randomisation For participants with T2D at screening, the following additional criterion applies: glycated haemoglobin (HbA1c) less than or equal to 10.0 percent (86 millimoles per mole [mmol/mol]) as measured by central laboratory at screening Exclusion Criteria: Treatment with any medication prescribed for the indication of obesity or weight management within 90 days before screening Previous or planned (during the study period) obesity treatment with surgery or a weight loss device. However, the following are allowed: a) liposuction and/or abdominoplasty, if performed greater than 1 year prior to screening. b) adjustable gastric banding, if the band has been removed greater than 1 year prior to screening. c) intragastric balloon, if the balloon has been removed greater than 1 year prior to screening. d)duodenal-jejunal bypass liner (e.g., nonbarrier), if the sleeve has been removed greater than 1 year prior to screening Type 1 diabetes mellitus or monogenic diabetes Participants with endocrine, hypothalamic, or syndromic obesity For participants with T2D at screening, the following additional key criterion applies: 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

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group Kids<br>Participants in the age group 6 to less than (<) 12 years will receive once weekly subcutaneous (s.c.) injection of either semaglutide or placebo matched to semaglutide in dose escalation fashion for 16 weeks (0.25 mg from weeks 0-4, 0.5 mg from weeks 5-8, 1.0 mg from weeks 9-12 and 1.7 mg from weeks 13-16) followed by 2.4 mg as maintenance dose for 88 weeks as an adjunct to a reduced-calorie diet and increased physical activity. | Drug: Semaglutide<br>* Semaglutide will be administered subcutaneously once weekly.<br>Drug: Placebo<br>* Placebo will be administered subcutaneously once-weekly.<br>|
| Experimental: Group Teens<br>Participants in the age group 12 to < 18 years will receive once weekly s.c. injection of either semaglutide or placebo matched to semaglutide in dose escalation fashion for 16 weeks (0.25 mg from weeks 0-4, 0.5 mg from weeks 5-8, 1.0 mg from weeks 9-12 and 1.7 mg from weeks 13-16) followed by 2.4 mg as maintenance dose for 88 weeks as an adjunct to a reduced-calorie diet and increased physical activity. | Drug: Semaglutide<br>* Semaglutide will be administered subcutaneously once weekly.<br>Drug: Placebo<br>* Placebo will be administered subcutaneously once-weekly.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Group Kids: Change in body mass index (BMI) | Measured in percentage (%) | From baseline (week 0) to week 68 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Group Kids: Improvement in weight category | Measured as count of participants. Weight categories based on growth charts from Center for Disease Control (CDC).gov: Normal weight= BMI less than (<) 85th percentile, Overweight= BMI greater than or equal to (>=) 85th - <95th percentile, Obesity class I= BMI >=95th - <120% of the 95th percentile, Obesity class II= BMI >=120% - <140% of the 95th percentile, Obesity class III= BMI >=140% of the 95th percentile. | From baseline (week 0) to week 68 | 
| Group Teens: Change in BMI | Measured in % | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in BMI | Measured in % | From week 0 to week 104 | 
| Group Teens: Improvement in weight category | Measured as count of participants. Weight categories based on growth charts from CDC.gov: Normal weight= BMI less than (<) 85th percentile, Overweight= BMI greater than or equal to (>=) 85th - <95th percentile, Obesity class I= BMI >=95th - <120% of the 95th percentile, Obesity class II= BMI >=120% - <140% of the 95th percentile, Obesity class III= BMI >=140% of the 95th percentile. | From week 0 to week 68 | 
| Group Kids and Group Teens: Improvement in weight category | Measured as count of participants. Weight categories based on growth charts from CDC.gov: Normal weight= BMI less than (<) 85th percentile, Overweight= BMI greater than or equal to (>=) 85th - <95th percentile, Obesity class I= BMI >=95th - <120% of the 95th percentile, Obesity class II= BMI >=120% - <140% of the 95th percentile, Obesity class III= BMI >=140% of the 95th percentile. | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in body weight | Measured in percentage | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in body weight | Measured in percentage | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in body weight | Measured in kilograms (kg) | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in body weight | Measured in kilograms (kg) | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in BMI percentage of the 95th percentile | Measured in percentage points | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in BMI percentage of the 95th percentile | Measured in percentage points | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in BMI Standard deviation score (SDS) | Measured as score on a scale. BMI SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a Z (SDS) score was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in BMI SDS | Measured as score in a scale. BMI SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a Z (SDS) score was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in waist circumference | Measured in centimeters (cm) | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in waist circumference | Measured in centimeters (cm) | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in systolic blood pressure | Measured in millimeters of mercury (mmHg) | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in systolic blood pressure | Measured in millimeters of mercury (mmHg) | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in diastolic blood pressure | Measured in mmHg | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in diastolic blood pressure | Measured in mmHg | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in total cholesterol | Measured in % | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in total cholesterol | Measured in % | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in high density lipoprotein (HDL) | Measured in % | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in high density lipoprotein (HDL) | Measured in % | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in low density lipoprotein (LDL) | Measured in % | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in low density lipoprotein (LDL) | Measured in % | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in very low density lipoprotein (VLDL) | Measured in % | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in very low density lipoprotein (VLDL) | Measured in % | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in triglycerides | Measured in % | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in triglycerides | Measured in % | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in high sensitivity C-reactive protein (hs-CRP) | Measured in % | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in high sensitivity C-reactive protein (hs-CRP) | Measured in % | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in glycated haemoglobin (HbA1c) | Measured in % point | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in glycated haemoglobin (HbA1c) | Measured in % point | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in fasting plasma glucose | Measured in millimoles per liter (mmol/L) | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in fasting plasma glucose | Measured in millimoles per liter (mmol/L) | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in fasting plasma glucose | Measured in milligrams per deciliter (mg/dL) | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in fasting plasma glucose | Measured in milligrams per deciliter (mg/dL) | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in fasting insulin | Measured in % | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in fasting insulin | Measured in % | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in alanine transaminase (ALT) | Measured in milliunits per liter (mU/L) | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in alanine transaminase (ALT) | Measured in milliunits per liter (mU/L) | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in total fat mass, by Dual energy X-ray absorptiometry (DXA) relative to total body mass | Measured in % points | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in total fat mass, by Dual energy X-ray absorptiometry (DXA) relative to total body mass | Measured in % points | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in lean body mass, by DXA relative to total body mass | Measured in % points | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in lean body mass, by DXA relative to total body mass | Measured in % points | From week 0 to week 104 | 
| Group Kids and Group Teens: Relative change in visceral fat mass by DXA | Measured in % | From week 0 to week 68 | 
| Group Kids and Group Teens: Relative change in visceral fat mass by DXA | Measured in % | From week 0 to week 104 | 
| Group Kids and Group Teens: Number of participants achieving greater than or equal to (>=) 5% reduction of BMI (yes/no) | Measured in count of participants | From week 0 to week 68 | 
| Group Kids and Group Teens: Number of participants achieving greater than or equal to (>=) 5% reduction of BMI (yes/no) | Measured in count of participants | From week 0 to week 104 | 
| Group Kids and Group Teens: Number of participants achieving greater than or equal to (>=) 10% reduction of BMI (yes/no) | Measured in count of participants | From week 0 to week 68 | 
| Group Kids and Group Teens: Number of participants achieving greater than or equal to (>=) 10% reduction of BMI (yes/no) | Measured in count of participants | From week 0 to week 104 | 
| Group Kids and Group Teens: Number of participants achieving greater than or equal to (>=) 15% reduction of BMI (yes/no) | Measured in count of participants | From week 0 to week 68 | 
| Group Kids and Group Teens: Number of participants achieving greater than or equal to (>=) 15% reduction of BMI (yes/no) | Measured in count of participants | From week 0 to week 104 | 
| Group Kids and Group Teens: Number of treatment emergent adverse events (AEs) | Measured as count of events | From week 0 to week 68 | 
| Group Kids and Group Teens: Number of treatment emergent adverse events (AEs) | Measured as count of events | From week 0 to week 111 | 
| Group Kids and Group Teens: Number of treatment emergent serious adverse events (SAEs) | Measured as count of events | From week 0 to week 68 | 
| Group Kids and Group Teens: Number of treatment emergent serious adverse events (SAEs) | Measured as count of events | From week 0 to week 111 | 
| Group Kids and Group Teens: Change in pulse | Measured as beats per minute | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in pulse | Measured as beats per minute | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in amylase | Measured as units per liter (U/L) | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in amylase | Measured as units per liter (U/L) | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in lipase | Measured as U/L | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in lipase | Measured as U/L | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in calcitonin | Measured as nanograms per liter (ng/L) | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in calcitonin | Measured as nanograms per liter (ng/L) | From week 0 to week 104 | 
| Group Kids and Group Teens: Change in bone mineral density, by DXA | Measured as grams per square centimeter (g/cm^2) | From week 0 to week 68 | 
| Group Kids and Group Teens: Change in bone mineral density, by DXA | Measured as grams per square centimeter (g/cm^2) | From week 0 to week 104 | 
| Group Kids and Group Teens: Number of treatment emergent hypoglycaemic episodes (for T2D only) | Measured as count of episodes | From week 0 to week 68 | 
| Group Kids and Group Teens: Number of treatment emergent hypoglycaemic episodes (for T2D only) | Measured as count of episodes | From week 0 to week 111 |