Research Study to Look at How Well Semaglutide is at Lowering Weight When Taken Together With an Intensive Lifestyle Program

Obesity Clinical Trial

— STEP 3  

Official title:

Effect and Safety of Semaglutide 2.4 mg Once-weekly as Adjunct to Intensive Behavioural Therapy in Subjects With Overweight or Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03611582
• Other study ID #: NN9536-4375
• Secondary ID: U1111-1200-8199
• Status: Completed
• Phase: Phase 3
• Start date: August 1, 2018
• Est. completion date: April 28, 2020

Study information

• Verified date: November 2021
• 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 participant's body weight from the start to the end of the study. This is to compare the effect on body weight in people taking semaglutide (a new medicine) and people taking "dummy" medicine. Together with the medicine, the participant will also be part of an intensive lifestyle program where the participant will have talks with study staff about healthy food choices, what the participant can do to lose weight and be more physically active. The participant will either get semaglutide or "dummy" medicine - which treatment the participant gets is decided by chance. The participant 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. For the first 2 months the participant will be on a low calorie diet. The diet is made up of bars, shakes and 1 low calorie pre-prepared meal for each day. The study will last for about 1.5 years. The participant will have 32 clinic visits with the study doctor.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 611
• Est. completion date: April 28, 2020
• Est. primary completion date: March 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years 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 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:

• Hemoglobin A1c 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
United States	Novo Nordisk Investigational Site	Albany	New York
United States	Novo Nordisk Investigational Site	Anaheim	California
United States	Novo Nordisk Investigational Site	Arlington	Virginia
United States	Novo Nordisk Investigational Site	Austin	Texas
United States	Novo Nordisk Investigational Site	Birmingham	Alabama
United States	Novo Nordisk Investigational Site	Chapel Hill	North Carolina
United States	Novo Nordisk Investigational Site	Charleston	South Carolina
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Endwell	New York
United States	Novo Nordisk Investigational Site	Escondido	California
United States	Novo Nordisk Investigational Site	Evanston	Illinois
United States	Novo Nordisk Investigational Site	Fresno	California
United States	Novo Nordisk Investigational Site	Fullerton	California
United States	Novo Nordisk Investigational Site	Golden	Colorado
United States	Novo Nordisk Investigational Site	Greensboro	North Carolina
United States	Novo Nordisk Investigational Site	Hickory	North Carolina
United States	Novo Nordisk Investigational Site	Honolulu	Hawaii
United States	Novo Nordisk Investigational Site	Huntington Beach	California
United States	Novo Nordisk Investigational Site	Kissimmee	Florida
United States	Novo Nordisk Investigational Site	Knoxville	Tennessee
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Montgomery	Alabama
United States	Novo Nordisk Investigational Site	Mount Pleasant	South Carolina
United States	Novo Nordisk Investigational Site	Newport News	Virginia
United States	Novo Nordisk Investigational Site	Olympia	Washington
United States	Novo Nordisk Investigational Site	Panama City	Florida
United States	Novo Nordisk Investigational Site	Peoria	Arizona
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Plantation	Florida
United States	Novo Nordisk Investigational Site	Raleigh	North Carolina
United States	Novo Nordisk Investigational Site	Rockwall	Texas
United States	Novo Nordisk Investigational Site	Roswell	Georgia
United States	Novo Nordisk Investigational Site	Round Rock	Texas
United States	Novo Nordisk Investigational Site	Saint George	Utah
United States	Novo Nordisk Investigational Site	Skokie	Illinois
United States	Novo Nordisk Investigational Site	Walnut Creek	California
United States	Novo Nordisk Investigational Site	Wilmington	North Carolina
United States	Novo Nordisk Investigational Site	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

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

Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O'Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT; STEP 3 Investigators. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Body Weight (%)	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 periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (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. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Baseline (week 0) to week 68
Primary	Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%	Number of participants who achieved greater than or equal to (=) 5% weight loss after 68 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 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.	After 68 weeks
Secondary	Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10%	Number of participants who achieved greater than or equal to (=) 10% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved = 10% weight loss whereas 'No' infers number of participants who have not achieved = 10% weight loss. 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).	After 68 weeks
Secondary	Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15%	Number of participants who achieved greater than or equal to (=) 15% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved = 15% weight loss whereas 'No' infers number of participants who have not achieved = 15% weight loss. 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).	After 68 weeks
Secondary	Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20%	Number of participants who achieved greater than or equal to (=) 20% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved = 20% weight loss whereas 'No' infers number of participants who have not achieved = 20% weight loss. 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).	After 68 weeks
Secondary	Change in Waist Circumference	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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Systolic Blood Pressure	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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Short Form-36 (SF-36) - Physical Functioning Score	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). The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Weight (Kg)	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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Body Mass Index	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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in HbA1c (%)	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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in HbA1c (mmol/Mol)	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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Fasting Plasma Glucose	Change in fasting plasma glucose from 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Fasting Serum Insulin	Change in fasting serum insulin from week 0 to week 68 [measured as milli-international units per milliliter (mIU/mL)] 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Diastolic Blood Pressure	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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Total Cholesterol	Change in fasting total cholesterol from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in High-density Lipoproteins (HDL)	Change in fasting HDL from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Low-density Lipoproteins (LDL)	Change in fasting LDL from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Very Low Density Lipoprotein (VLDL)	Change in fasting VLDL from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Free Fatty Acids	Change in fasting free fatty acids from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Triglycerides	Change in fasting triglycerides from baseline (week 0) to week 68 (measured as mg/dL) 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in High Sensitivity C-reactive Protein	Change in high sensitivity C-reactive protein 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Change in Plasminogen Activator Inhibitor-1 Activity	Change in plasminogen activator inhibitor-1 activity 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 68
Secondary	Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score	The observed number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on two 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 overweight or obese population included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on Food and Drug Administration (FDA) recommendations. In the reported data, "Yes" infers 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 uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).	After 68 weeks
Secondary	Change in Body Weight	Change in body weight from baseline (week 0) to week 8 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 randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0) to week 8
Secondary	Number of Treatment-emergent Adverse Events (AEs)	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 that had onset date (or increase in severity) on or after the first day of exposure to treatment. 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).	Baseline (week 0) to week 75
Secondary	Number of Serious Adverse Events (SAEs)	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).	Baseline (week 0) to week 75
Secondary	Change in Pulse	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).	Baseline (week 0) to week 68
Secondary	Change in Amylase	Change in amylase (measured as 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).	Baseline (week 0) to week 68
Secondary	Change in Lipase	Change in lipase (measured as 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).	Baseline (week 0) to week 68
Secondary	Change in Calcitonin	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).	Baseline (week 0) to week 68