A Research Study on How Well Semaglutide Works in Adolescents With Overweight or Obesity

Study Overview
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Brief Summary
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This study will look at the change in teenagers' body weight from the start to the end of the study. This is to compare the effect on body weight in teenagers taking semaglutide (a new medicine) and teenagers taking dummy medicine. The teenagers in the study and their parents will also have talks with study staff about healthy food choices, how to be more physically active and what they can do to help the teenagers lose weight. The teenagers will either get semaglutide or dummy medicine - which treatment is decided by chance. The teenagers will take 1 injection every week, on the same day of the week for about 15 months. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. The teenagers will have 17 clinic visits, will have blood samples taken and will have to complete questionnaires and keep a diary. All this will be explained before study start.

Official Title
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Effect and Safety of Semaglutide 2.4 mg Once Weekly on Weight Management in Adolescents With Overweight or Obesity

Conditions
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Overweight, Obesity

Intervention / Treatment
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* Drug: Semaglutide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent of parent(s) or legally acceptable representative of subject and child assent, as appropriate 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, ages 12 to below 18 years at the time of signing informed consent BMI equal to or above 95th percentile OR equal to or above 85th percentile (on gender and age-specific growth charts (CDC.gov)) with 1 or more weight related comorbidity (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or type 2 diabetes History of at least one self-reported unsuccessful dietary effort to lose weight For subjects with type 2 diabetes at screening the following inclusion criteria apply in addition: - HbA1c equal to or below 10.0% (86 mmol/mol) as measured by central laboratory at screening Exclusion Criteria: Prepubertal subjects (Tanner stage 1) History of type 1 diabetes A self-reported (or by parent(s)/legally acceptable representative where applicable) change in body weight above 5 kg (11 lbs) within 90 days before screening irrespective of medical records Subjects with secondary causes of obesity (i.e., hypothalamic, monogenic or endocrine causes) For subjects with type 2 diabetes only: Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide<br>2.4 mg or maximum tolerated dose (MTD) injected subcutaneously (under the skin, s.c.) once weekly | Drug: Semaglutide<br>* Participants will receive semaglutide s.c. once weekly for a dose escalation period of 16 weeks and a maintenance period of 52 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo injected s.c. once weekly . | Other: Placebo<br>* Participants will receive semaglutide placebo s.c. once weekly for a total of 68 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Mass Index (BMI) (Percentage [%]) | Change in BMI (%) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Greater Than or Equal to (>=) 5% Reduction of Body Weight (Yes/no) | Percentage of participants who achieved >= 5% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the percentage of participants who have achieved >= 5% weight reduction, whereas 'No' infers the percentage of participants who did not achieve >= 5% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to last contact with trial site. | At week 68 | 
| Change in Body Weight (Kilograms [kg]) | Change in body weight (kg) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Body Weight (%) | Change in body weight (%) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Percentage of Participants Achieving >=10% Reduction of Body Weight (Yes/no) | Percentage of participants who achieved >= 10% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the percentage of participants who have achieved >= 10% weight reduction, whereas 'No' infers the percentage of participants who did not achieve >= 10% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to last contact with trial site. | At week 68 | 
| Percentage of Participants Achieving >=15% Reduction of Body Weight (Yes/no) | Percentage of participants who achieved >= 15% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the percentage of participants who have achieved >= 15% weight reduction, whereas 'No' infers the percentage of participants who did not achieve >= 15% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to last contact with trial site. | At week 68 | 
| Percentage of Participants Achieving >=20% Reduction of Body Weight (Yes/no) | Percentage of participants who achieved >= 20% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the percentage of participants who have achieved >= 20% weight reduction, whereas 'No' infers the percentage of participants who did not achieve >= 20% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to last contact with trial site. | At week 68 | 
| Change in BMI Percentage of the 95th Percentile on Gender and Age-specific Growth Charts (CDC.Gov [CDC: {Centers for Disease Control and Prevention}]) | Change from baseline in BMI percentage of the 95th percentile on gender and age-specific growth charts (CDC.gov) at week 68 is presented. CDC gender and age-specific growth charts: normal (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% of the 95th percentile - <140% of the 95th percentile) and obesity class III (BMI >=140% of the 95th percentile). Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Percentage of Participants Achieving Improvement in Weight Category (Yes/no) | Percentage of participants who achieved improvement in weight category from baseline (week 0) to week 68 is presented. Improvement in weight category was defined as being in a lower weight category at week 68 compared to baseline according to CDC gender and age-specific growth charts: normal (BMI <85th percentile), overweight (BMI >=85th - <95th percentile), obesity class I (BMI >=95th - <120% of the 95th percentile), obesity class II (BMI >=120% of the 95th percentile - <140% of the 95th percentile) and obesity class III (BMI >=140% of the 95th percentile). In the reported data, 'Yes' infers the percentage of participants who have achieved improvement in weight category, whereas 'No' infers the percentage of participants who did not achieve improvement in weight category. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | At week 68 | 
| Change in BMI (Standard Deviation Score [SDS]) | Change in BMI SDS from baseline to week 68 is presented. The SDS scores are also called as z-scores. 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 standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the world health organisation (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. Possible values range from -3 to +3, a negative score being beneficial. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in BMI (Kilograms Per Meter Square [kg/m^2]) | Change in BMI (kg/m^2) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Waist Circumference | Change in waist circumference (centimeters [cm]) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Percentage of Participants Achieving >=5% Reduction of BMI (Yes/no) | Percentage of participants who achieved >= 5% reduction of BMI from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the percentage of participants who have achieved >= 5% BMI reduction, whereas 'No' infers the percentage of participants who did not achieve >= 5% BMI reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to last contact with trial site. | At week 68 | 
| Change in Systolic Blood Pressure | Change in systolic blood pressure from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Diastolic Blood Pressure | Change in diastolic blood pressure from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Glycated Haemoglobin (HbA1c) (%) | Change in HbA1c (%) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in HbA1c (Millimoles Per Mole [mmol/Mol]) | Change in HbA1c (mmol/mol) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Fasting Plasma Glucose (Millimoles Per Liter [mmol/L]) | Change in fasting plasma glucose (mmol/L) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Fasting Plasma Glucose (Milligrams Per Deciliter [mg/dL]) | Change in fasting plasma glucose (mg/dL) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Fasting Insulin (Picomoles Per Liter [Pmol/L]): Ratio to Baseline | Change in fasting insulin (pmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Fasting Insulin (Milli International Units Per Milliliter [mIU/mL]): Ratio to Baseline | Change in fasting insulin (mIU/mL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Total Cholesterol (mmol/L): Ratio to Baseline | Change in total cholesterol (mmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Total Cholesterol (mg/dL): Ratio to Baseline | Change in total cholesterol (mg/dL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in High-density Lipoprotein (HDL) Cholesterol (mmol/L): Ratio to Baseline | Change in HDL cholesterol (mmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68: | 
| Change in High-density Lipoprotein (HDL) Cholesterol (mg/dL): Ratio to Baseline | Change in HDL cholesterol (mg/dL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Low-density Lipoprotein (LDL) Cholesterol (mmol/L): Ratio to Baseline | Change in LDL cholesterol (mmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in LDL Cholesterol (mg/dL): Ratio to Baseline | Change in LDL cholesterol (mg/dL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68: | 
| Change in Very Low-density Lipoprotein (VLDL) Cholesterol (mmol/L): Ratio to Baseline | Change in VLDL cholesterol (mmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in VLDL Cholesterol (mg/dL): Ratio to Baseline | Change in VLDL cholesterol (mg/dL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Triglycerides (mmol/L): Ratio to Baseline | Change in triglycerides (mmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Triglycerides (mg/dL): Ratio to Baseline | Change in triglycerides (mg/dL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Change in Alanine Aminotransferase (ALT): Ratio to Baseline | Change in ALT (units per liter [U/L]) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site. | Baseline (week 0), week 68 | 
| Number of Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was any untoward medical occurrence in a clinical trial participant administered or using a medicinal product, whether or not considered related to the medicinal product or usage. All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. The on-treatment period was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as greater than (>) 7 consecutive missed doses (corresponding to >7 weeks off-treatment). | From baseline (week 0) to week 75 | 
| Number of Treatment-emergent Serious Adverse Events (SAEs) | An SAE is an AE that fulfils at least one of the following criteria: 1) results in death; 2) is life-threatening; 3) requires inpatient hospitalisation or prolongation of existing hospitalisation; 4) results in persistent disability/incapacity; 5) is a congenital anomaly/birth defect; 6) important medical event. All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. The on-treatment period was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment). | From baseline (week 0) to week 75 | 
| Change in Pulse | Change in pulse from baseline to week 68 is presented. Data is reported for on-treatment period: the on-treatment period was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment). | Baseline (week 0), week 68 | 
| Change in Amylase: Ratio to Baseline | Change in amylase (U/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for on-treatment period: the on-treatment period was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment). | Baseline (week 0), week 68 | 
| Change in Lipase: Ratio to Baseline | Change in lipase (U/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for on-treatment period: the on-treatment period was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment). | Baseline (week 0), week 68 | 
| Change in Calcitonin: Ratio to Baseline | Change in calcitonin (nanograms per liter [ng/L]) from baseline to week 68 is presented as ratio to baseline. Data is reported for on-treatment period: the on-treatment period was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment). | Baseline (week 0), week 68 |