Two-year Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity

Obesity Clinical Trial

— STEP 5  

Official title:

Two-year Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03693430
• Other study ID #: NN9536-4378
• Secondary ID: 2017-003726-32U1
• Status: Completed
• Phase: Phase 3
• Start date: October 5, 2018
• Est. completion date: March 23, 2021

Study information

• Verified date: July 2023
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will look at the change in body weight from the start to the end of the study. Researchers will compare the weight loss in people taking semaglutide (a new medicine) to people taking "dummy" medicine. In addition to taking the medicine, participants will also have talks with study staff about healthy food choices, how the participant can be more physically active and what participants can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment the participant gets 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 will last for about 2 years. The participants will have 19 clinic visits and 15 phone calls with the study doctor.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 304
• Est. completion date: March 23, 2021
• Est. primary completion date: January 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Male or female, age more than or equal to 18 years at the time of signing informed consent
• Body mass index (BMI) more than or equal to 30 kg/m^2 or more than or equal to 27 kg/m^2 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

Exclusion criteria:

• HbA1c more than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening
• A self-reported change in body weight more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Related Conditions & MeSH terms

• Obesity
• Overweight

Intervention

Drug:
• Semaglutide
Subcutaneous (s.c., under the skin) injections of semaglutide once weekly at escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks
• Placebo (Semaglutide)
S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks

Locations

Country	Name	City	State
Canada	Novo Nordisk Investigational Site	Halifax	Nova Scotia
Canada	Novo Nordisk Investigational Site	Hamilton	Ontario
Canada	Novo Nordisk Investigational Site	Hamilton	Ontario
Canada	Novo Nordisk Investigational Site	Moncton	New Brunswick
Canada	Novo Nordisk Investigational Site	Montreal	Quebec
Canada	Novo Nordisk Investigational Site	Quebec
Canada	Novo Nordisk Investigational Site	Surrey	British Columbia
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Debrecen
Hungary	Novo Nordisk Investigational Site	Komarom
Hungary	Novo Nordisk Investigational Site	Szekszárd
Italy	Novo Nordisk Investigational Site	Bologna
Italy	Novo Nordisk Investigational Site	Palermo
Italy	Novo Nordisk Investigational Site	Pisa
Italy	Novo Nordisk Investigational Site	Rome
Italy	Novo Nordisk Investigational Site	Siena
Spain	Novo Nordisk Investigational Site	Alcorcón
Spain	Novo Nordisk Investigational Site	Almeria
Spain	Novo Nordisk Investigational Site	Hospitalet de Llobregat
Spain	Novo Nordisk Investigational Site	Pamplona
Spain	Novo Nordisk Investigational Site	Pozuelo de Alarcon
Spain	Novo Nordisk Investigational Site	Sevilla
United States	Novo Nordisk Investigational Site	Albany	New York
United States	Novo Nordisk Investigational Site	Arlington	Virginia
United States	Novo Nordisk Investigational Site	Aurora	Colorado
United States	Novo Nordisk Investigational Site	Austin	Texas
United States	Novo Nordisk Investigational Site	Birmingham	Alabama
United States	Novo Nordisk Investigational Site	Butte	Montana
United States	Novo Nordisk Investigational Site	Golden	Colorado
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Kingsport	Tennessee
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Ocala	Florida
United States	Novo Nordisk Investigational Site	Rochester	New York
United States	Novo Nordisk Investigational Site	Round Rock	Texas
United States	Novo Nordisk Investigational Site	Saint Peters	Missouri
United States	Novo Nordisk Investigational Site	Waterbury	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Canada,  Hungary,  Italy,  Spain, 

References & Publications (2)

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. — View Citation

Wharton S, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jodar E, Kandler K, Rigas G, Wadden TA, Garvey WT. Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/obesity: STEP 5. Obesity (Silver Spring). 2023 Mar;31(3):703-715. doi: 10.1002/oby.23673. Epub 2023 Jan 18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage Change From Baseline (Week 0) to Week 104 in Body Weight	Percentage change in body weight for both in-trial and on-treatment observation period from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: 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).	From Baseline (Week 0) to Week 104
Primary	Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5%	Number of participants who achieved greater than or equal to (>=) 5% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=5% weight loss, whereas 'No' infers the number of participants who have not achieved >=5% weight loss. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: 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).	At Week 104
Secondary	Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%	Number of participants who achieved >=10% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	At Week 104
Secondary	Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%	Number of participants who achieved >=15% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	At Week 104
Secondary	Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%	Number of participants who achieved >=20% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	At Week 104
Secondary	Change From Baseline (Week 0) to Week 104 in Waist Circumference	Change in waist circumference from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change From Baseline (Week 0) to Week 104 in Body Weight (kg)	Change in body weight from baseline (week 0) to week 104 in kilogram (kg) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change From Baseline (Week 0) to Week 104 in Body Mass Index (BMI)	Change in BMI from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change From Baseline (Week 0) to Week 104 in Systolic Blood Pressure	Change in systolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change From Baseline (Week 0) to Week 104 in Diastolic Blood Pressure	Change in diastolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change in Total Cholesterol-ratio to Baseline	Change in total cholesterol from baseline (week 0) to week 104 measured in milligrams per deciliter (mg/dL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change in High Density Lipoprotein (HDL) Cholesterol-ratio to Baseline	Change in HDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change in Low Density Lipoprotein (LDL) Cholesterol-ratio to Baseline	Change in LDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change in Very Low Density Lipoprotein (VLDL) Cholesterol-ratio to Baseline	Change in VLDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change in Free Fatty Acids-ratio to Baseline	Change in free fatty acids from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change in Triglycerides-ratio to Baseline	Change in triglycerides from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline	Change in hsCRP from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change in Glycated Haemoglobin (HbA1c) (Percent [%])	Change in HbA1c from baseline (week 0) to week 104 in % is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change From Baseline (Week 0) to Week 104 in HbA1c (mmol/Mol)	Change in HbA1c from baseline (week 0) to week 104 in millimole per mole (mmol/mol) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change From Baseline (Week 0) to Week 104 in Fasting Plasma Glucose (FPG) (mmol/L)	Change in FPG from baseline (week 0) to week 104 in millimoles per liter (mmol/L) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change From Baseline (Week 0) to Week 104 in FPG (mg/dL)	Change in FPG from baseline (week 0) to week 104 in mg/dL is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change in Fasting Serum Insulin-ratio to Baseline (Pmol/L)	Change in fasting serum insulin from baseline (week 0) to week 104 measured in picomole per liter (pmol) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Change in Fasting Serum Insulin-ratio to Baseline (mIU/mL)	Change in fasting serum insulin from baseline (week 0) to week 104 measured in milli-international units per milliliter (mIU/mL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.	From Baseline (Week 0) to Week 104
Secondary	Percentage Change From Baseline (Week 0) to Week 52 in Body Weight	Percentage change in body weight from baseline (week 0) to week 52 is presented.	From Baseline (Week 0) to Week 52
Secondary	Change From Baseline (Week 0) to Week 52 in Body Weight (kg)	Change in body weight from baseline (week 0) to week 52 in kg is presented.	From Baseline (Week 0) to Week 52
Secondary	Change From Baseline (Week 0) to Week 52 in Body Mass Index (BMI)	Change in BMI from baseline (week 0) to week 52 is presented.	From Baseline (Week 0) to Week 52
Secondary	Change From Baseline (Week 0) to Week 52 in Waist Circumference	Change in waist circumference from baseline (week 0) to week 52 is presented.	From Baseline (Week 0) to Week 52
Secondary	Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5%	Number of participants who achieved >=5% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=5% weight loss, whereas 'No' infers the number of participants who have not achieved >=5% weight loss.	At Week 52
Secondary	Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%	Number of participants who achieved >=10% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss.	At Week 52
Secondary	Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%	Number of participants who achieved >=15% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss.	At Week 52
Secondary	Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%	Number of participants who achieved >=20% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss.	At Week 52
Secondary	Number of Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any unfavourable 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 TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment. The outcome measure was evaluated based on the data from on-treatment observation period, which 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 111
Secondary	Number of Serious Adverse Events (SAEs)	A SAE was 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 111 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which 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 111
Secondary	Change From Baseline (Week 0) to Week 104 in Pulse	Change in pulse from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which 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).	From Baseline (Week 0) to Week 104
Secondary	Change From Baseline (Week 0) to Week 104 in Amylase	Change in amylase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which 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).	From Baseline (Week 0) to Week 104
Secondary	Change From Baseline (Week 0) to Week 104 in Lipase	Change in lipase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which 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).	From Baseline (Week 0) to Week 104
Secondary	Change From Baseline (Week 0) to Week 104 in Calcitonin	Change in calcitonin from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which 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).	From Baseline (Week 0) to Week 104