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

• ClinicalTrials.gov Identifier: NCT04102189
• Recruitment Status: Completed
• First Posted: September 25, 2019
• Results First Posted: April 18, 2023
• Last Update Posted: April 18, 2023
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: September 23, 2019
• First Posted Date: September 25, 2019
• Results First Submitted Date: March 24, 2023
• Results First Posted Date: April 18, 2023
• Last Update Posted Date: April 18, 2023
• Actual Study Start Date: October 7, 2019
• Actual Primary Completion Date: March 25, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 24, 2023)

Change in Body Mass Index (BMI) (Percentage [%]) [ Time Frame: Baseline (week 0), week 68 ]

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.

Original Primary Outcome Measures (submitted: September 23, 2019)

Change in Body Mass Index (BMI) [ Time Frame: From baseline (week 0) to week 68 ]

Percent

Current Secondary Outcome Measures (submitted: March 24, 2023)

• Percentage of Participants Achieving Greater Than or Equal to (>=) 5% Reduction of Body Weight (Yes/no) [ Time Frame: At week 68 ]
  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.
• Change in Body Weight (Kilograms [kg]) [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Body Weight (%) [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Percentage of Participants Achieving >=10% Reduction of Body Weight (Yes/no) [ Time Frame: At week 68 ]
  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.
• Percentage of Participants Achieving >=15% Reduction of Body Weight (Yes/no) [ Time Frame: At week 68 ]
  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.
• Percentage of Participants Achieving >=20% Reduction of Body Weight (Yes/no) [ Time Frame: At week 68 ]
  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.
• Change in BMI Percentage of the 95th Percentile on Gender and Age-specific Growth Charts (CDC.Gov [CDC: {Centers for Disease Control and Prevention}]) [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Percentage of Participants Achieving Improvement in Weight Category (Yes/no) [ Time Frame: At week 68 ]
  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.
• Change in BMI (Standard Deviation Score [SDS]) [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in BMI (Kilograms Per Meter Square [kg/m^2]) [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Waist Circumference [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Percentage of Participants Achieving >=5% Reduction of BMI (Yes/no) [ Time Frame: At week 68 ]
  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.
• Change in Systolic Blood Pressure [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Diastolic Blood Pressure [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Glycated Haemoglobin (HbA1c) (%) [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in HbA1c (Millimoles Per Mole [mmol/Mol]) [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Fasting Plasma Glucose (Millimoles Per Liter [mmol/L]) [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Fasting Plasma Glucose (Milligrams Per Deciliter [mg/dL]) [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Fasting Insulin (Picomoles Per Liter [Pmol/L]): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Fasting Insulin (Milli International Units Per Milliliter [mIU/mL]): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Total Cholesterol (mmol/L): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Total Cholesterol (mg/dL): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in High-density Lipoprotein (HDL) Cholesterol (mmol/L): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68: ]
  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.
• Change in High-density Lipoprotein (HDL) Cholesterol (mg/dL): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Low-density Lipoprotein (LDL) Cholesterol (mmol/L): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in LDL Cholesterol (mg/dL): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68: ]
  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.
• Change in Very Low-density Lipoprotein (VLDL) Cholesterol (mmol/L): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in VLDL Cholesterol (mg/dL): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Triglycerides (mmol/L): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Triglycerides (mg/dL): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Change in Alanine Aminotransferase (ALT): Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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.
• Number of Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From baseline (week 0) to week 75 ]
  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).
• Number of Treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: From baseline (week 0) to week 75 ]
  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).
• Change in Pulse [ Time Frame: Baseline (week 0), week 68 ]
  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).
• Change in Amylase: Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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).
• Change in Lipase: Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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).
• Change in Calcitonin: Ratio to Baseline [ Time Frame: Baseline (week 0), week 68 ]
  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).

Original Secondary Outcome Measures (submitted: September 23, 2019)

• Subjects achieving a reduction of body weight equal to or above 5 percent [ Time Frame: From baseline (week 0) to week 68 ]
  Yes/no
• Change in body weight [ Time Frame: From baseline (week 0) to week 68 ]
  Kg
• Change in body weight [ Time Frame: From baseline (week 0) to week 68 ]
  Percent
• Change in BMI percentage of the 95th percentile on gender and age-specific growth charts (CDC.gov) [ Time Frame: From baseline (week 0) to week 68 ]
  Percent
• Change in BMI (standard deviation score) (WHO.int) [ Time Frame: From baseline (week 0) to week 68 ]
  Score
• Change in waist circumference [ Time Frame: From baseline (week 0) to week 68 ]
  Cm
• Change in systolic blood pressure [ Time Frame: From baseline (week 0) to week 68 ]
  mmHg
• Change in diastolic blood pressure [ Time Frame: From baseline (week 0) to week 68 ]
  mmHg
• Change in glycosylated haemoglobin (HbA1c) [ Time Frame: From baseline (week 0) to week 68 ]
  Percentage points
• Subjects achieving a reduction of BMI equal to or above 5 percent [ Time Frame: From baseline (week 0) to week 68 ]
  Yes/no
• Number of treatment-emergent adverse events (TEAEs) [ Time Frame: From baseline (week 0) to week 75 ]
  Count
• Number of treatment-emergent serious adverse events (SAEs) [ Time Frame: From baseline (week 0) to week 75 ]
  Count
• Change in pulse [ Time Frame: From baseline (week 0) to week 68 ]
  Bpm
• Change in amylase [ Time Frame: From baseline (week 0) to week 68 ]
  U/L
• Change in lipase [ Time Frame: From baseline (week 0) to week 68 ]
  U/L
• Change in calcitonin [ Time Frame: From baseline (week 0) to week 68 ]
  ng/L

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Research Study on How Well Semaglutide Works in Adolescents With Overweight or Obesity
• Official Title: Effect and Safety of Semaglutide 2.4 mg Once Weekly on Weight Management in Adolescents With Overweight or Obesity
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Sponsor staff involved in the clinical trial is masked according to company standard procedures

Primary Purpose: Treatment

Condition

• Overweight
• Obesity

Intervention

• Drug: Semaglutide
  Participants will receive semaglutide s.c. once weekly for a dose escalation period of 16 weeks and a maintenance period of 52 weeks
• Other: Placebo
  Participants will receive semaglutide placebo s.c. once weekly for a total of 68 weeks

Study Arms

• Experimental: Semaglutide
  2.4 mg or maximum tolerated dose (MTD) injected subcutaneously (under the skin, s.c.) once weekly
  Intervention: Drug: Semaglutide
• Placebo Comparator: Placebo
  Placebo injected s.c. once weekly .
  Intervention: Other: Placebo

Publications *

• Weghuber D, Barrett T, Barrientos-Perez M, Gies I, Hesse D, Jeppesen OK, Kelly AS, Mastrandrea LD, Sorrig R, Arslanian S; STEP TEENS Investigators. Once-Weekly Semaglutide in Adolescents with Obesity. N Engl J Med. 2022 Dec 15;387(24):2245-2257. doi: 10.1056/NEJMoa2208601. Epub 2022 Nov 2.
• Cuda S, Censani M. Progress in pediatric obesity: new and advanced therapies. Curr Opin Pediatr. 2022 Aug 1;34(4):407-413. doi: 10.1097/MOP.0000000000001150. Epub 2022 Jul 5.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 24, 2023): 201
• Original Estimated Enrollment (submitted: September 23, 2019): 192
• Actual Study Completion Date: March 28, 2022
• Actual Primary Completion Date: March 25, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Croatia, Ireland, Mexico, Russian Federation, United Kingdom, United States

Administrative Information

• NCT Number: NCT04102189
• Other Study ID Numbers: NN9536-4451; U1111-1215-7560 ( Other Identifier: World Health Organization (WHO) ); 2018-002431-18 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://novonordisk-trials.com

• Current Responsible Party: Novo Nordisk A/S
• Original Responsible Party: Same as current
• Current Study Sponsor: Novo Nordisk A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452); Novo Nordisk A/S

• PRS Account: Novo Nordisk A/S
• Verification Date: March 2023