STEP 1: Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity (STEP 1)

• ClinicalTrials.gov Identifier: NCT03548935
• Recruitment Status: Completed
• First Posted: June 7, 2018
• Results First Posted: August 11, 2021
• Last Update Posted: November 19, 2021
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: May 25, 2018
• First Posted Date: June 7, 2018
• Results First Submitted Date: June 16, 2021
• Results First Posted Date: August 11, 2021
• Last Update Posted Date: November 19, 2021
• Actual Study Start Date: June 4, 2018
• Actual Primary Completion Date: March 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 16, 2021)

• Change in Body Weight (%) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from date of randomization (week 0) to date of last contact with trial site (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
• Participants Who Achieve 5 or More Percent Body Weight Reduction (Yes/no) [ Time Frame: After week 68 ]
  Number of participants who achieved weight loss more than or equal to 5% (yes/no) at week 68 are presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption.

Original Primary Outcome Measures (submitted: May 25, 2018)

• Change in body weight [ Time Frame: Week 0, Week 68 ]
  Measured in %.
• Subjects who achieve 5 or more percent body weight reduction (yes/no) [ Time Frame: Week 68 ]
  Number of subjects.

Current Secondary Outcome Measures (submitted: June 16, 2021)

• Subjects Who Achieve 10 or More Percent Body Weight Reduction (Yes/no) [ Time Frame: Week 68 ]
  Number of participants who achieved weight loss more than or equal to (≥) 10% at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from date of randomization (week 0) to date of last contact with trial site (week 75).
• Participants Who Achieve 15 or More Percent Body Weight Reduction (Yes/no) [ Time Frame: Week 68 ]
  Number of participants who achieved more than or equal to (≥) 15% weight loss at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Participants Who Achieve 20 or More Percent Body Weight Reduction (Yes/no) [ Time Frame: Week 68 ]
  Number of participants who achieved more than or equal to (≥) 20% weight loss at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Waist Circumference (cm) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in waist circumference from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to date of last contact with trial site (week 75).
• Change in Systolic Blood Pressure (mmHg) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to date of last contact with trial site (week 75).
• Change in Short Form 36 (SF-36) [ Time Frame: Baseline (week 0) to week 68 ]
  SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation, respectively, for the 2009 US general population. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Impact of Weight on Quality of Life-Lite for Clinical Trial (IWQoL-Lite for CT) Score [ Time Frame: Baseline (week 0) to week 68 ]
  IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. It is used to assess the impact of body weight changes on patients' physical and psychosocial functioning in three composite scores (physical function, physical and psychosocial) and a total score. The scores range between 0-100 where higher scores indicate a better quality of life. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Body Weight (kg) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Body Mass Index (BMI) (kg/m2) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in body mass index from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in HbA1C (%) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in HbA1C (mmol/Mol) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in HbA1c from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Fasting Plasma Glucose (FPG) (mg/dL) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in fasting plasma glucose from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Fasting Serum Insulin (mIU/L) - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in fasting serum insulin from week 0 to week 68 is presented as ratio to baseline. Fasting serum insulin was measured in milli-international units per milliliter (mIU/mL). The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Diastolic Blood Pressure (mmHg) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Total Cholesterol (mg/dL) - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in fasting total cholesterol from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in High-density Lipoproteins (HDL) (mg/dL) - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in fasting HDL from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Low-density Lipoproteins (LDL) (mg/dL) - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in fasting LDL from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Very Low-density Lipoproteins (VLDL) (mg/dL) - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in fasting VLDL from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Free Fatty Acids (mg/dL) - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in fasting free fatty acids from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Triglycerides (mg/dL) - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in fasting triglycerides from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in High Sensitivity C-Reactive Protein (hsCRP) - (mg/L) - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in high sensitivity C-reactive protein from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Plasminogen Activator Inhibitor-1 (PAI-1) Activity (AU/ml) - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in plasminogen activator inhibitor-1 activity from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Soluble Leptin Receptor (ng/mL) - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in soluble leptin receptor from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Leptin (ng/mL) - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in leptin from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Body Composition (Total Fat Mass) (%) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in body composition (total fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using Dual Energy X-ray Absorpmetry (DEXA). The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Body Composition (Total Fat Mass) (kg) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in body composition (total fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using Dual Energy X-ray Absorpmetry (DEXA). The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Body Composition (Lean Body Mass) (%) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in body composition (lean body mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Body Composition (Lean Body Mass) (kg) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in body composition (lean body mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Body Composition (Visceral Fat Mass) (%) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in body composition (visceral fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Body Composition (Visceral Fat Mass) (kg) [ Time Frame: Baseline (week 0) to week 68 ]
  Change in body composition (visceral fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Body Weight (%) - DEXA Subpopulation [ Time Frame: Baseline (week 0) to week 68 ]
  Change in body weight from baseline (week 0) to week 68 is presented in DEXA subpopulation. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Change in Body Weight (kg) - DEXA Subpopulation [ Time Frame: Baseline (week 0) to week 68 ]
  Change in body weight from baseline (week 0) to week 68 is presented in DEXA subpopulation. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
• Participants Who Achieve "Responder Definition Value" (Yes/no) for SF-36 Physical Functioning Score [ Time Frame: After week 68 ]
  The observed number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on two different thresholds. The threshold of 4.3 is the default generic responder threshold defined in SF-36 manual for a general population. The threshold of 3.7 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on FDA recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on the in-trial observation period which is the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).
• Participants Who Achieve "Responder Definition Value" (Yes/no) for IWQoL-Lite for CT Physical Function Domain (5-items) Score [ Time Frame: After week 68 ]
  The observed number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 68 weeks was determined based on two different thresholds. The threshold of 20 was a preliminary responder threshold based on earlier studies. The threshold of 14.6 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on FDA recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers the number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on the in-trial observation period. In trial observation period: the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).
• Number of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline (week 0) to week 75 ]
  An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event for which the onset of the event occurs in the on-treatment period. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).
• Number of Serious Adverse Events (SAEs) [ Time Frame: Baseline (week 0) to week 75 ]
  A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. The SAEs occurred from week 0 to week 75 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).
• Change in Pulse [ Time Frame: Baseline (week 0) to week 68 ]
  Change in pulse from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
• Change in Amylase - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in amylase (measured as units per litre [U/L]) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
• Change in Lipase - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in lipase (measured as units per litre [U/L]) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
• Change in Calcitonin - Ratio to Baseline [ Time Frame: Baseline (week 0) to week 68 ]
  Change in calcitonin (measured as ng/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).

Original Secondary Outcome Measures (submitted: May 25, 2018)

• Subjects who achieve 10 or more percent body weight reduction (yes/no) [ Time Frame: Week 68 ]
  Number of subjects.
• Subjects who achieve 15 or more percent body weight reduction (yes/no) [ Time Frame: Week 68 ]
  Number of subjects.
• Change in waist circumference [ Time Frame: Week 0, Week 68 ]
  Measured in cm.
• Change in systolic blood pressure [ Time Frame: Week 0, Week 68 ]
  Measured in mmHg.
• Change in physical functioning score (SF-36) [ Time Frame: Week 0, Week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.
• Change in physical function domain (5-item) score (IWQoL-Lite for CT) [ Time Frame: Week 0, Week 68 ]
  The Impact of Weight on Quality of Life Lite for Clinical Trials Version (IWQoL-Lite for CT) questionnaire is a 20-item modified version of an instrument designed to assess weight-related quality of life.
• Change in body weight [ Time Frame: Week 0, Week 68 ]
  Measured in kg.
• Change in body mass index (BMI) [ Time Frame: Week 0, Week 68 ]
  Measured in kg/m2
• Change in glycated haemoglobin (HbA1C) [ Time Frame: Week 0, Week 68 ]
  Measured in %.
• Change in HbA1C [ Time Frame: Week 0, Week 68 ]
  Measured in mmol/mol.
• Change in fasting plasma glucose (FPG) [ Time Frame: Week 0, Week 68 ]
  Measured in mg/dL.
• Change in fasting serum insulin [ Time Frame: Week 0, Week 68 ]
  Measured in mIU/L.
• Change in diastolic blood pressure [ Time Frame: Week 0, Week 68 ]
  Measured in mmHg.
• Change in lipids (total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, free fatty acids and triglycerides) [ Time Frame: Week 0, Week 68 ]
  Measured in mg/dL.
• Change in high sensitivity C-Reactive Protein (hsCRP) [ Time Frame: Week 0, Week 68 ]
  Measured in mg/L.
• Change in plasminogen activator inhibitor-1 (PAI-1) activity [ Time Frame: Week 0, Week 68 ]
  Measured in AU/mL.
• Change in soluble leptin receptor [ Time Frame: Week 0, Week 68 ]
  Measured in ng/mL.
• Change in leptin [ Time Frame: Week 0, Week 68 ]
  Measured in ng/mL.
• Change in SF-36 (role-physical score) [ Time Frame: Week 0, Week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.
• Change in SF-36 (bodily pain score) [ Time Frame: Week 0, Week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.
• Change in SF-36 (general health score) [ Time Frame: Week 0, Week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.
• Change in SF-36 (vitality score) [ Time Frame: Week 0, Week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.
• Change in SF-36 (social functioning score) [ Time Frame: Week 0, Week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.
• Change in SF-36 (role-emotional score) [ Time Frame: Week 0, Week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.
• Change in SF-36 (mental health score) [ Time Frame: Week 0, Week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.
• Change in SF-36 (physical component summary) [ Time Frame: Week 0, Week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.
• Change in SF-36 (mental component summary) [ Time Frame: Week 0, Week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.
• Change in IWQoL-Lite for CT (pain/discomfort domain score) [ Time Frame: Week 0, Week 68 ]
  The Impact of Weight on Quality of Life Lite for Clinical Trials Version (IWQoL-Lite for CT) questionnaire is a 20-item modified version of an instrument designed to assess weight-related quality of life.
• Change in IWQoL-Lite for CT (psychosocial domain score) [ Time Frame: Week 0, Week 68 ]
  The Impact of Weight on Quality of Life Lite for Clinical Trials Version (IWQoL-Lite for CT) questionnaire is a 20-item modified version of an instrument designed to assess weight-related quality of life.
• Change in IWQoL-Lite for CT (total score) [ Time Frame: Week 0, Week 68 ]
  The Impact of Weight on Quality of Life Lite for Clinical Trials Version (IWQoL-Lite for CT) questionnaire is a 20-item modified version of an instrument designed to assess weight-related quality of life.
• Change in body composition (total fat mass) [ Time Frame: Week 0, Week 68 ]
  Assessed by dual energy X-ray absorpmetry (DEXA). Measured in %.
• Change in body composition (total fat mass) [ Time Frame: Week 0, Week 68 ]
  Assessed by DEXA. Measured in g.
• Change in body composition (lean body mass) [ Time Frame: Week 0, Week 68 ]
  Assessed by DEXA. Measured in %.
• Change in body composition (lean body mass) [ Time Frame: Week 0, Week 68 ]
  Assessed by DEXA. Measured in g.
• Change in body composition (visceral fat mass) [ Time Frame: Week 0, Week 68 ]
  Assessed by DEXA. Measured in %.
• Change in body composition (visceral fat mass) [ Time Frame: Week 0, Week 68 ]
  Assessed by DEXA. Measured in g.
• Subjects who achieve "responder definition value" (yes/no) for SF-36 physical functioning score [ Time Frame: Week 68 ]
  Number of subjects.
• Subjects who achieve "responder definition value" (yes/no) for IWQoL-Lite for CT physical function domain (5-items) score [ Time Frame: Week 68 ]
  Number of subjects.
• Number of treatment emergent adverse events (TEAEs) [ Time Frame: Weeks 0 to 75 ]
  Number of events.
• Number of serious adverse events (SAEs) [ Time Frame: Weeks 0 to 75 ]
  Number of events.
• Change in pulse [ Time Frame: Week 0, Week 68 ]
  Measured in bpm.
• Change in amylase [ Time Frame: Week 0, Week 68 ]
  Measured in U/L.
• Change in lipase [ Time Frame: Week 0, Week 68 ]
  Measured in U/L.
• Change in calcitonin [ Time Frame: Week 0, Week 68 ]
  Measured in ng/L.

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

Descriptive Information

• Brief Title: STEP 1: Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity
• Official Title: Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity
• Brief Summary: This study will look at the change in participants' body weight from the start to the end of the study. The weight loss in participants taking semaglutide (a new medicine) will be compared to the weight loss of participants taking "dummy" medicine. In addition to taking the medicine, participants will have talks with study staff about healthy food choices, how to be more physically active and what you can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment participants get, is decided by chance. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. The study has two phases: A main phase and an extension phase.The main phase will last for about 1.5 years. Participants will have 15 clinic visits and 10 phone calls with the study doctor. Extension phase: Approximately 300 participants will continue in the extension phase in the following countries only: Canada, Germany, the UK and selected sites in the US and Japan. These participants will be in the study for about 2.5 years.They will not receive treatment, but will attend another 5 follow-up visits with the study doctor.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

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

Primary Purpose: Treatment

Condition

• Metabolism and Nutrition Disorder
• Overweight or Obesity

Intervention

• Drug: Semaglutide
  Participants will receive semaglutide subcutaneous (s.c.; under the skin) injection(s) once-weekly as well as diet and physical activity counselling for 68 weeks. Dose escalation of semaglutide will take place as follows: 0.25 mg from week 1 to 4, 0.5 mg from week 5 to 8, 1.0 mg from week 9 to 12, 1.7 mg from week 13 to 16 and 2.4 mg from week 17 to week 68.
• Drug: Placebo (semaglutide)
  Participants will receive semaglutide matching placebo s.c. injection(s) once-weekly as well as diet and physical activity counselling for 68 weeks.

Study Arms

• Experimental: Semaglutide s.c. 2.4 mg once weekly
  Participants will receive semaglutide for 68 weeks.
  Intervention: Drug: Semaglutide
• Placebo Comparator: Semaglutide placebo
  Participants will receive semaglutide matching placebo for 68 weeks.
  Intervention: Drug: Placebo (semaglutide)

Publications *

• Kushner RF, Calanna S, Davies M, Dicker D, Garvey WT, Goldman B, Lingvay I, Thomsen M, Wadden TA, Wharton S, Wilding JPH, Rubino D. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring). 2020 Jun;28(6):1050-1061. doi: 10.1002/oby.22794.
• Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.
• Kosiborod MN, Bhatta M, Davies M, Deanfield JE, Garvey WT, Khalid U, Kushner R, Rubino DM, Zeuthen N, Verma S. Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses. Diabetes Obes Metab. 2023 Feb;25(2):468-478. doi: 10.1111/dom.14890. Epub 2022 Oct 28.
• Perreault L, Davies M, Frias JP, Laursen PN, Lingvay I, Machineni S, Varbo A, Wilding JPH, Wallenstein SOR, le Roux CW. Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program. Diabetes Care. 2022 Oct 1;45(10):2396-2405. doi: 10.2337/dc21-1785.
• Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Rosenstock J, Wadden TA, Wharton S, Yokote K, Kushner RF; STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564. doi: 10.1111/dom.14725. Epub 2022 May 19.
• O'Neil PM, Birkenfeld AL, McGowan B, Mosenzon O, Pedersen SD, Wharton S, Carson CG, Jepsen CH, Kabisch M, Wilding JPH. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2. Epub 2018 Aug 16.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 22, 2021): 1961
• Original Estimated Enrollment (submitted: May 25, 2018): 1950
• Actual Study Completion Date: March 5, 2021
• Actual Primary Completion Date: March 30, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Main phase:

• Male or female, age greater than or equal to 18 years at the time of signing informed consent
• Body mass index (BMI) greater than or equal to 30.0 kg/sqm or greater than or equal to 27.0 kg/sqm with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease
• History of at least one self-reported unsuccessful dietary effort to lose body weight

Extension phase:

• Informed consent for the extension phase obtained before any trial related activities for the extension phase
• On randomised treatment on the target dose at week 68, i.e. treated with 2.4 mg semaglutide once-weekly or semaglutide placebo

Exclusion Criteria:

Main phase:

• Glycated haemoglobin (HbA1C) greater than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening
• A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Extension phase:

• Female who is pregnant or intends to become pregnant during the extension phase
• Any disorder, unwillingness or inability, not covered by any of the other exclusion criteria, which in the investigator's opinion, might jeopardise the subject's compliance with the extension of the trial

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Belgium, Bulgaria, Canada, Denmark, Finland, France, Germany, India, Japan, Mexico, Poland, Puerto Rico, Russian Federation, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03548935
• Other Study ID Numbers: NN9536-4373; U1111-1200-8053 ( Other Identifier: World Health Organization (WHO) ); 2017-003436-36 ( Registry Identifier: European Medicines Agency (EudraCT) )
• Has Data Monitoring Committee: No

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/sharing-results

• 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: November 2021