A Research Study to See How Semaglutide Helps People With Excess Weight, Lose Weight (STEP UP)

Study Overview
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Brief Summary
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This study will look at how much weight participants will lose from the start to the end of the study. The weight loss in participants taking the investigational high dose of semaglutide will be compared to the weight loss in people taking dummy medicine and a lower dose of semaglutide. In addition to taking the medicine, participants will have talks with study staff about healthy food choices and how to be more physically active. Participants will either get semaglutide or dummy medicine. Which treatment participants get is decided by chance. Participants are more likely (4 out of 5) to get semaglutide than the dummy medicine. The study medicine will be injected briefly, under skin, with a thin needle, typically in the stomach, thighs, or upper arms. In the first part of the study, participants will get one injection once a week until they reach the planned dose. The second part of the study, which might last a couple of months, is a transition period, where participant will get three injections, taken right after each other, once a week. The duration of the study intervention (trial product and lifestyle intervention) will be 72 weeks followed by a 9-week follow-up period without study interventions.

Official Title
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Effect and Safety of Semaglutide 7.2 mg Once-weekly in Participants With Obesity

Conditions
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Obesity

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female. Age above or equal to 18 years at the time of signing informed consent. Body mass index (BMI) greater than or equal to 30.0 kilogram per square meter (kg/m^2). History of at least one self-reported unsuccessful dietary effort to lose body weight. Exclusion Criteria: HbA1c greater than or equal to 48 millimoles per mole (mmol/mol) (6.5 percent) as measured by the central laboratory at screening. History of type 1 or type 2 diabetes. Treatment with glucose-lowering agent(s) within 90 days before screening. A self-reported change in body weight greater than 5 kilograms (kg) (11 pounds) within 90 days before screening irrespective of medical records. Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide 7.2 mg<br>Participants will receive once-weekly injection of semaglutide subcutaneously (s.c.) in 20 week dose escalation period with dose escalation (0.25 milligram [mg], 0.5 mg, 1.0 mg, 1.7 mg, 2.4 mg, and 7.2 mg) every fourth week. Treatment was continued on the maintenance dose of 7.2 mg once-weekly for an additional 52 weeks until week 72. | Drug: Semaglutide<br>* Participants will receive once-weekly s.c. injections of semaglutide in escalating doses (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, 2.4 mg and 7.2 mg) every fourth week. Treatment was continued on the maintenance dose of 7.2 mg once-weekly for an additional 52 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.<br>|
| Experimental: Semaglutide 2.4 mg<br>Participants will receive once-weekly s.c. injection of semaglutide in 20 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once-weekly for an additional 52 weeks until week 72. | Drug: Semaglutide<br>* Participants will receive once-weekly s.c. injections of semaglutide in escalating doses (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg) every fourth week. Treatment was continued on the maintenance dose of 2.4 mg once-weekly for an additional 52 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.<br>|
| Placebo Comparator: Placebo<br>Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks. | Drug: Placebo<br>* Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Semaglutide 7.2 mg versus Placebo: Relative change in body weight | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction greater than or equal to (>=) 5% (yes/no) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction >=10% (yes/no) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction >=15% (yes/no) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction >=20% (yes/no) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction >=25% (yes/no) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in waist circumference | Measured in centimeters (cm). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Relative change in body weight | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Number of participants who achieve body weight reduction >=20% (yes/no) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Number of participants who achieve body weight reduction >=25% (yes/no) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in body weight | Measured in kilograms (kg). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in body mass index (BMI) | Measured in kilogram per square meter (kg/m^2). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in total fat mass (%) | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in total fat mass (liters) | Measured in liters. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in lean body mass (%) | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in lean body mass (liters) | Measured in liters. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in visceral fat mass (%) | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in visceral fat mass (liters) | Measured in liters. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in systolic blood pressure | Measured in millimeters of mercury (mmHg). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in diastolic blood pressure | Measured in mmHg. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in total cholesterol | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in high-density lipoprotein (HDL) cholesterol | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in low-density lipoprotein (LDL) cholesterol | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in very low-density lipoprotein (VLDL) cholesterol | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in triglycerides | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in free fatty acids | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in high-sensitivity c reactive protein (hsCRP) | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants with change in lipid-lowering treatment (decrease, no change, increase) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants with change in antihypertensive treatment (decrease, no change, increase) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in glycated haemoglobin (HbA1c) | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in fasting plasma glucose | Measured in milligrams per deciliter (mg/dL). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in fasting serum insulin | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants with change in glycaemic category (Normo-glycaemia, pre-diabetes, type 2 diabetes [T2D]) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of adverse events (AEs) | Measured as count of events. | From baseline (week 0) to end of study (week 81) | 
| Semaglutide 7.2 mg versus Placebo: Number of serious adverse events (SAEs) | Measured as count of events. | From baseline (week 0) to end of study (week 81) | 
| Semaglutide 7.2 mg versus Placebo: Change in pulse | Measured in beats per minute (bmp). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Number of AEs | Measured as count of events. | From baseline (week 0) to end of study (week 81) | 
| Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Number of SAEs | Measured as count of events. | From baseline (week 0) to end of study (week 81) |