Metabolism and Nutrition DisorderPhase 3STEP 4NCT03548987
Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity
A Phase 3 study testing Semaglutide in people with Metabolism and Nutrition Disorder and Obesity, run by Novo Nordisk A/S at 72 sites in 10 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metabolism and Nutrition Disorder, Obesity
- What is being tested?
- Semaglutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 902 participants
- Where
- 72 sitesin 10 countries
- Study dates
- 4 Jun 2018to 20 Mar 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, age greater than or equal to 18 years at the time of signing informed consent
- Body mass index greater than or equal to 30 kg/sqm or greater than or equal to 27 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
Who cannot join
- Haemoglobin A1c greater than or equal to 48 mmol/mol (6.5%) as measured by 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
Trial locations and contacts
72 sites in 10 countries.
72 sites in 10 countries
United States28 sites
Novo Nordisk Investigational Site
Alpharetta, Georgia, 30022
Novo Nordisk Investigational Site
Anniston, Alabama, 36207
Novo Nordisk Investigational Site
Arlington, Virginia, 22206
Novo Nordisk Investigational Site
Austin, Texas, 78731
Novo Nordisk Investigational Site
Baton Rouge, Louisiana, 70808
Novo Nordisk Investigational Site
Bristol, Tennessee, 37620-7352
Novo Nordisk Investigational Site
Bristol, Tennessee, 37620
Novo Nordisk Investigational Site
Buckley, Michigan, 49620
Novo Nordisk Investigational Site
Chattanooga, Tennessee, 37404
Novo Nordisk Investigational Site
Cincinnati, Ohio, 45242
Novo Nordisk Investigational Site
Dallas, Texas, 75226
Novo Nordisk Investigational Site
Dallas, Texas, 75230
Novo Nordisk Investigational Site
Dallas, Texas, 75231
Novo Nordisk Investigational Site
Dayton, Ohio, 45406
Novo Nordisk Investigational Site
Elkridge, Maryland, 21075-6437
Novo Nordisk Investigational Site
Fresno, California, 93720
Novo Nordisk Investigational Site
Greensboro, North Carolina, 27408
Novo Nordisk Investigational Site
Greenville, North Carolina, 27834
Novo Nordisk Investigational Site
Louisville, Kentucky, 40213
Novo Nordisk Investigational Site
New York, New York, 10016
Novo Nordisk Investigational Site
Omaha, Nebraska, 68198-3020
Novo Nordisk Investigational Site
Raleigh, North Carolina, 27612
Novo Nordisk Investigational Site
Richmond, Virginia, 23226
Novo Nordisk Investigational Site
Roswell, Georgia, 30076
Novo Nordisk Investigational Site
Salisbury, North Carolina, 28144
Novo Nordisk Investigational Site
San Diego, California, 92108
Novo Nordisk Investigational Site
Suwanee, Georgia, 30024
Novo Nordisk Investigational Site
Wenatchee, Washington, 98801-2028
Spain7 sites
Novo Nordisk Investigational Site
Almería, 04009
Novo Nordisk Investigational Site
Madrid, 28009
Novo Nordisk Investigational Site
Madrid, 28040
Novo Nordisk Investigational Site
Sabadell, 08208
Novo Nordisk Investigational Site
Seville, 41003
Novo Nordisk Investigational Site
Seville, 41009
Novo Nordisk Investigational Site
Seville, 41013
Israel6 sites
Novo Nordisk Investigational Site
Haifa, 35152
Novo Nordisk Investigational Site
Jerusalem, 91120
Novo Nordisk Investigational Site
Kfar Saba, 44281
Novo Nordisk Investigational Site
Petah Tikva, 49372
Novo Nordisk Investigational Site
Tel Aviv, 64239
Novo Nordisk Investigational Site
Tel HaShomer, 52621
Portugal6 sites
Novo Nordisk Investigational Site
Braga, 4710-243
Novo Nordisk Investigational Site
Coimbra, 3000-561
Novo Nordisk Investigational Site
Matosinhos Municipality, 4464-513
Novo Nordisk Investigational Site
Porto, 4099-001
Novo Nordisk Investigational Site
Porto, 4200-319
Novo Nordisk Investigational Site
Vila Nova de Gaia, 4400-346
South Africa6 sites
Novo Nordisk Investigational Site
Brits, North West, 0250
Novo Nordisk Investigational Site
Durban, KwaZulu-Natal, 4001
Novo Nordisk Investigational Site
Johannesburg, Gauteng, 2001
Novo Nordisk Investigational Site
Johannesburg, Gauteng, 2013
Novo Nordisk Investigational Site
Pretoria, Gauteng, 0181
Novo Nordisk Investigational Site
Pretoria, Gauteng, 0184
Switzerland6 sites
Novo Nordisk Investigational Site
Geneva, 1211
Novo Nordisk Investigational Site
Olten, 4600
Novo Nordisk Investigational Site
Sankt Gallen, 9007
Novo Nordisk Investigational Site
Sankt Gallen, 9016
Novo Nordisk Investigational Site
Zollikerberg, 8125
Novo Nordisk Investigational Site
Zurich, 8091
Ukraine5 sites
Novo Nordisk Investigational Site
Kharkiv, 61039
Novo Nordisk Investigational Site
Kyiv, 03039
Novo Nordisk Investigational Site
Kyiv, 04050
Novo Nordisk Investigational Site
Kyiv, 04114
Novo Nordisk Investigational Site
Odesa, 65059
Netherlands3 sites
Novo Nordisk Investigational Site
Amsterdam, 1066 EC
Novo Nordisk Investigational Site
Amsterdam, 1105 AZ
Novo Nordisk Investigational Site
Arnhem, 6815 AD
Sweden3 sites
Novo Nordisk Investigational Site
Malmö, 205 02
Novo Nordisk Investigational Site
Stockholm, 141 86
Novo Nordisk Investigational Site
Uppsala, 751 85
Denmark2 sites
Novo Nordisk Investigational Site
Frederiksberg C, 1958
Novo Nordisk Investigational Site
Køge, 4600
About this study
Official title: Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity Who Have Reached Target Dose During run-in Period
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. In addition to taking the medicine, the participant will have talks with study staff about healthy food choices, how to be more physically active and what a participant can do to lose weight.
The participant will get semaglutide for the first 20 weeks. Then the participant will get either semaglutide or "dummy" medicine - which treatment the participant gets after the 20 weeks is decided by chance. The 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 1.5 years.
- Conditions
- Metabolism and Nutrition Disorder, Obesity
- Being tested
- Semaglutide, Placebo
- Medical subject headings
- Nutrition Disorders, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SemaglutideDrug
Subcutaneous (under the skin) injection of semaglutide once-weekly.
PlaceboDrug
Subcutaneous (under the skin) injection of semaglutide placebo once-weekly.
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide | Experimental | Run-in Period: Participants will receive semaglutide at an escalating doses (0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg) for 20 weeks (week 0 to week 20). The dose will be escalated to next level every 4 weeks.
Maintenance period: Participants will be randomized to receive semaglutide injection for 48 weeks (from week 20 to week 68).
The trial product will be administered as an adjunct to a reduced-calorie diet and increased physical activity during the trial period. Receives: Drug: Semaglutide |
| Placebo | Placebo comparator | Run-in Period: Participants will receive semaglutide at an escalating doses (0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg) for 20 weeks (week 0 to week 20). The dose will be escalated to next level every 4 weeks.
Maintenance period: Participants will be randomized to receive semaglutide placebo injection for 48 weeks (from week 20 to week 68).
The trial product will be administered as an adjunct to a reduced-calorie diet and increased physical activity during the trial period. Receives: Drug: Semaglutide; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Randomisation to Week 68 in Body Weight (%)
Change in body weight from baseline (week 20) 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 start of run-in (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).
Measured: Randomisation (week 20) to week 68
Secondary outcomes (36)
Change in Waist Circumference
Change in waist circumference from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Systolic Blood Pressure
Change in systolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Diastolic Blood Pressure
Change in diastolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Physical Functioning Score (Short Form 36 [SF-36])
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 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Body Weight [Kilogram (Kg)]
Change in body weight from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomisation (week 20) to week 68
Change in Body Mass Index (BMI)
Change in BMI from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Haemoglobin A1c (HbA1c) [%]
Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in HbA1c [Millimoles Per Mole (mmol/Mol)]
Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)]
Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)]
Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Fasting Serum Insulin
Change in fasting serum insulin from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Total Cholesterol
Change in fasting total cholesterol from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in High-density Lipoproteins (HDL)
Change in fasting HDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Low-density Lipoproteins (LDL)
Change in fasting LDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Very Low-density Lipoproteins (VLDL)
Change in fasting VLDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Free Fatty Acids
Change in fasting free fatty acids from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Change in Triglycerides
Change in fasting triglycerides from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomization (week 20) to week 68
Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score
The number of participants achieving at least a 4.3-point increase in SF-36 physical functioning score from baseline (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved 4.3 points of increase of the score and 'No' infers number of participants who have not achieved 4.3 points of increase of the score. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomisation (week 20) to week 68
Subjects Who Gain Weight (Yes/no)
The number of participants with weight gain from the start of the randomised period (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have gained weight and 'No' infers number of participants who have not gained weight. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Randomisation (week 20) to week 68
Change in Body Weight
The body weight change (%) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction < 0%
The number of participants who achieved less than (<) 0% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved <0% weight loss whereas 'No' infers number of participants who have not achieved <0% 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5%
The number of participants who achieved greater than or equal to (≥) 5% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 5% weight loss whereas 'No' infers number of participants who have not achieved ≥ 5% 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10%
The number of participants who achieved ≥ 10% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15%
The number of participants who achieved ≥ 15% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Measured: Run-in (week 0) to week 68
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 (week 0-20 run-in 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).
Measured: Run-in (week 0) to randomisation (week 20)
Number of Treatment-emergent AEs
An 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 TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment (week 20-75). 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).
Measured: Randomisation (week 20) to week 75
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 during run-in period from week 0 to week 20 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).
Measured: Run-in (week 0) to randomisation (week 20)
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 during run-in period from week 0 to week 20 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).
Measured: Randomisation (week 20) to week 75
Change in Pulse
Change in pulse rate from week 0 week to week 20 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).
Measured: Run-in (week 0) to randomisation (week 20)
Change in Pulse
Change in pulse from week 20 and 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).
Measured: Randomisation (week 20) to week 68
Change in Amylase
Change in amylase (measured as units per liter [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).
Measured: Run-in (week) 0 to randomization (week 20)
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).
Measured: Randomisation (week 20) to week 68
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).
Measured: Run-in (week 0) to randomization (week 20)
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).
Measured: Randomisation (week 20) to week 68
Change in Calcitonin
Change in calcitonin (measured as nanogram per liter (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).
Measured: Run-in (week 0) to randomization (week 20)
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).
Measured: Randomisation (week 20) to week 68
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2018
- Study start4 Jun 2018
- Primary completion22 Feb 2020
- Study completion20 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Metabolism and Nutrition DisorderStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 902 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Reporting Anchor and Disclosure (1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03548987
- Sponsor's protocol ID
- NN9536-4376
- Other IDs
- U1111-1201-0898, 2017-003473-34, 2017
- Acronym
- STEP 4
- Status last verified
- Jan 2022
- First submitted
- 25 May 2018
- Last updated
- 19 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
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.
PubMed 32441473Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, Lingvay I, Mosenzon O, Rosenstock J, Rubio MA, Rudofsky G, Tadayon S, Wadden TA, Dicker D; STEP 4 Investigators. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1414-1425. doi: 10.1001/jama.2021.3224.
PubMed 33755728Rubino D, Bjorner JB, Rathor N, Sharma AM, von Huth Smith L, Wharton S, Wadden T, Zeuthen N, Kolotkin RL. Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: Patient-reported outcomes from the STEP 1-4 trials. Diabetes Obes Metab. 2024 Jul;26(7):2945-2955. doi: 10.1111/dom.15620. Epub 2024 May 2.
PubMed 38698650Wilkinson L, Holst-Hansen T, Laursen PN, Rinnov AR, Batterham RL, Garvey WT. Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity. Obesity (Silver Spring). 2023 Sep;31(9):2249-2259. doi: 10.1002/oby.23842.
PubMed 37605636Kosiborod 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.
PubMed 36200477Perreault 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.
PubMed 35724304O'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.
PubMed 30122305
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity Who Have Reached Target Dose During run-in Period
- ClinicalTrials.gov ID
- NCT03548987
- Acronym / sponsor ID
- STEP 4 / NN9536-4376
- Conditions
- Metabolism and Nutrition Disorder, Obesity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 902 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 4 Jun 2018 (actual)
- Primary completion
- 22 Feb 2020 (actual)
- Study completion
- 20 Mar 2020 (actual)
- First posted
- 7 Jun 2018 (actual)
- Results
- Posted 15 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. In addition to taking the medicine, the participant will have talks with study staff about healthy food choices, how to be more physically active and what a participant can do to lose weight.
The participant will get semaglutide for the first 20 weeks. Then the participant will get either semaglutide or "dummy" medicine - which treatment the participant gets after the 20 weeks is decided by chance. The 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 1.5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Semaglutide | Experimental | Drug: SemaglutideRun-in Period: Participants will receive semaglutide at an escalating doses (0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg) for 20 weeks (week 0 to week 20). The dose will be escalated to next level every 4 weeks. Maintenance period: Participants will be randomized to receive semaglutide injection for 48 weeks (from week 20 to week 68). The trial product will be administered as an adjunct to a reduced-calorie diet and increased physical activity during the trial period. |
| Placebo | Placebo comparator | Drug: Semaglutide, Drug: PlaceboRun-in Period: Participants will receive semaglutide at an escalating doses (0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg) for 20 weeks (week 0 to week 20). The dose will be escalated to next level every 4 weeks. Maintenance period: Participants will be randomized to receive semaglutide placebo injection for 48 weeks (from week 20 to week 68). The trial product will be administered as an adjunct to a reduced-calorie diet and increased physical activity during the trial period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female, age greater than or equal to 18 years at the time of signing informed consent
- Body mass index greater than or equal to 30 kg/sqm or greater than or equal to 27 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
Key exclusion criteria (2 listed)
- Haemoglobin A1c greater than or equal to 48 mmol/mol (6.5%) as measured by 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SemaglutideSubcutaneous (under the skin) injection of semaglutide once-weekly. | Drug | Placebo, Semaglutide |
| PlaceboSubcutaneous (under the skin) injection of semaglutide placebo once-weekly. | Drug | Placebo |
Primary outcome
Change From Randomisation to Week 68 in Body Weight (%)
Time frame: Randomisation (week 20) to week 68
Change in body weight from baseline (week 20) 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 start of run-in (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).
36 secondary outcomes
Change in Waist Circumference
Time frame: Randomization (week 20) to week 68
Change in Systolic Blood Pressure
Time frame: Randomization (week 20) to week 68
Change in Diastolic Blood Pressure
Time frame: Randomization (week 20) to week 68
Change in Physical Functioning Score (Short Form 36 [SF-36])
Time frame: Randomization (week 20) to week 68
Change in Body Weight [Kilogram (Kg)]
Time frame: Randomisation (week 20) to week 68
Change in Body Mass Index (BMI)
Time frame: Randomization (week 20) to week 68
Change in Haemoglobin A1c (HbA1c) [%]
Time frame: Randomization (week 20) to week 68
Change in HbA1c [Millimoles Per Mole (mmol/Mol)]
Time frame: Randomization (week 20) to week 68
Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)]
Time frame: Randomization (week 20) to week 68
Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)]
Time frame: Randomization (week 20) to week 68
Change in Fasting Serum Insulin
Time frame: Randomization (week 20) to week 68
Change in Total Cholesterol
Time frame: Randomization (week 20) to week 68
Change in High-density Lipoproteins (HDL)
Time frame: Randomization (week 20) to week 68
Change in Low-density Lipoproteins (LDL)
Time frame: Randomization (week 20) to week 68
Change in Very Low-density Lipoproteins (VLDL)
Time frame: Randomization (week 20) to week 68
Change in Free Fatty Acids
Time frame: Randomization (week 20) to week 68
Change in Triglycerides
Time frame: Randomization (week 20) to week 68
Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score
Time frame: Randomisation (week 20) to week 68
Subjects Who Gain Weight (Yes/no)
Time frame: Randomisation (week 20) to week 68
Change in Body Weight
Time frame: Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction < 0%
Time frame: Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5%
Time frame: Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10%
Time frame: Run-in (week 0) to week 68
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15%
Time frame: Run-in (week 0) to week 68
Number of Treatment-emergent Adverse Events (AEs)
Time frame: Run-in (week 0) to randomisation (week 20)
Number of Treatment-emergent AEs
Time frame: Randomisation (week 20) to week 75
Number of Serious Adverse Events (SAEs)
Time frame: Run-in (week 0) to randomisation (week 20)
Number of Serious Adverse Events (SAEs)
Time frame: Randomisation (week 20) to week 75
Change in Pulse
Time frame: Run-in (week 0) to randomisation (week 20)
Change in Pulse
Time frame: Randomisation (week 20) to week 68
Change in Amylase
Time frame: Run-in (week) 0 to randomization (week 20)
Change in Amylase
Time frame: Randomisation (week 20) to week 68
Change in Lipase
Time frame: Run-in (week 0) to randomization (week 20)
Change in Lipase
Time frame: Randomisation (week 20) to week 68
Change in Calcitonin
Time frame: Run-in (week 0) to randomization (week 20)
Change in Calcitonin
Time frame: Randomisation (week 20) to week 68
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32441473Kushner 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.
- Results publication: PubMed 33755728Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, Lingvay I, Mosenzon O, Rosenstock J, Rubio MA, Rudofsky G, Tadayon S, Wadden TA, Dicker D; STEP 4 Investigators. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1414-1425. doi: 10.1001/jama.2021.3224.
- Derived from this study: PubMed 38698650Rubino D, Bjorner JB, Rathor N, Sharma AM, von Huth Smith L, Wharton S, Wadden T, Zeuthen N, Kolotkin RL. Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: Patient-reported outcomes from the STEP 1-4 trials. Diabetes Obes Metab. 2024 Jul;26(7):2945-2955. doi: 10.1111/dom.15620. Epub 2024 May 2.
- Derived from this study: PubMed 37605636Wilkinson L, Holst-Hansen T, Laursen PN, Rinnov AR, Batterham RL, Garvey WT. Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity. Obesity (Silver Spring). 2023 Sep;31(9):2249-2259. doi: 10.1002/oby.23842.
- Derived from this study: PubMed 36200477Kosiborod 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.
- Derived from this study: PubMed 35724304Perreault 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.
- Derived from this study: PubMed 30122305O'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.
- Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Related trials for Metabolism and Nutrition Disorder
RecruitingObservational study
Endoscopic Sleeve Gastroplasty (ESG) Prospective Trial for Obesity (EGO-Trial)
Obesity
Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
RecruitingPhase 1/2
A First-in-human Study of KK8123 in Adults With X-linked Hypophosphatemia
X-linked Hypophosphatemia
Recruiting
Exercise Training and Vitamin D Metabolism
Obesity & Overweight, Vitamin D
Recruiting
Metabolic Health, Bones and Nuts During Weight Loss in Adults
Weight Loss, Bone Density
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Reporting Anchor and Disclosure (1452) study director
Novo Nordisk A/S
72 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Semaglutide in people with Metabolism and Nutrition Disorder and Obesity, run by Novo Nordisk A/S at 72 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 72 sites in United States, Spain, Israel, Portugal, South Africa and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Randomisation to Week 68 in Body Weight (%) (time frame: Randomisation (week 20) to week 68). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03548987, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2022.