STEP 6: Research Study Investigating How Well Semaglutide Works in People Living With Overweight or Obesity

Obesity Clinical Trial

— STEP 6  

Official title:

Effect and Safety of Semaglutide Once-weekly in East Asian Subjects With Overweight or Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03811574
• Other study ID #: NN9536-4382
• Secondary ID: U1111-1201-1629
• Status: Completed
• Phase: Phase 3
• Start date: January 21, 2019
• Est. completion date: November 20, 2020

Study information

• Verified date: February 2022
• 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 participants' 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, participants will have talks with study staff about healthy food choices, how to be more physically active and what participants can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment participants get is decided by chance. Participants are three times as likely to get semaglutide as "dummy" medicine. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skinfold in the stomach, thigh or upper arm. The study will last for about one and a half years. Participants will have 14 clinic visits and 11 phone calls with the study doctor.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 401
• Est. completion date: November 20, 2020
• Est. primary completion date: November 20, 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

• BMI more than or equal to 27.0 kg/m^2 with more than or equal to 2 weight related comorbidities (treated or untreated) or BMI more than or equal to 35.0 kg/m^2 with more than or equal to 1 weight related comorbidity (treated or untreated) according to the JASSO guideline. At least one comorbidity should be hypertension or dyslipidaemia (Japan only: or T2D)

• History of at least one self-reported unsuccessful dietary effort to lose body weight

• For subjects with T2D at screening (Japan only): a) Diagnosed with T2D more than or equal to 180 days prior to the day of screening. b) HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive)

Exclusion Criteria:

• A self-reported change in body weight more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

• For subjects without T2D at screening: HbA1c more than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening

• For subjects with T2D at screening (Japan only): a) Renal impairment measured as estimated glomerular filtration rate (eGFR) value of less than 30 mL/min/1.73 m^2 (less than 60 mL/min/1.73 m^2 in subjects treated with sodium-glucose co-transporter 2 inhibitor (SGLT2i)) according to chronic kidney disease epidemiology (CKD-EPI) creatinine equation as defined by kidney disease improving global outcome (KDIGO) 2012 by the central laboratory at screening. b) Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation

Related Conditions & MeSH terms

• Obesity
• Overweight

Intervention

Drug:
• Semaglutide
Semaglutide injections will be administered once-weekly by a pre-filled pen-injector at the same day of the week (to the extent possible). Injections may be administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals.
• Placebo (semaglutide)
Placebo (semaglutide) injections will be administered once-weekly by a pre-filled pen-injector at the same day of the week (to the extent possible). Injections may be administered in the thigh, abdomen or upper arm, at any time of day irrespective of meals.

Locations

Country	Name	City	State
Japan	Novo Nordisk Investigational Site	Adachi-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Bunkyo-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Chitose, Hokkaido
Japan	Novo Nordisk Investigational Site	Chuo-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Chuo-ku,Tokyo
Japan	Novo Nordisk Investigational Site	Gunma
Japan	Novo Nordisk Investigational Site	Ibaraki
Japan	Novo Nordisk Investigational Site	Kanagawa
Japan	Novo Nordisk Investigational Site	Kashiwara-shi, Osaka
Japan	Novo Nordisk Investigational Site	Kobe, Hyogo
Japan	Novo Nordisk Investigational Site	Kumamoto
Japan	Novo Nordisk Investigational Site	Miyazaki
Japan	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Shimotsuke-shi, Tochigi
Japan	Novo Nordisk Investigational Site	Suita-shi, Osaka
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Toyama-shi, Toyama
Japan	Novo Nordisk Investigational Site	Yamato-shi, Kanagawa
Korea, Republic of	Novo Nordisk Investigational Site	Gyeonggi-do
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Yangsan

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

Japan,  Korea, Republic of, 

References & Publications (1)

Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I; STEP 2 Study Group. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a ra — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Body Weight (%)	Change from baseline (week 0) in body weight for 'in-trial' observation period at week 68 is presented. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75).	Baseline (week 0), week 68
Primary	Number of 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 at week 68 for in-trial observation period 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. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75).	At week 68
Secondary	Number of 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 at week 68 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 endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.	At week 68
Secondary	Number of 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 at week 68 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 endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization to last trial-related subject-site contact.	At week 68
Secondary	Number of 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 at week 68 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 endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.	At week 68
Secondary	Change in Waist Circumference Measured Midway Between the Lower Rib Margin and the Iliac Crest	Change in waist circumference measured midway between the lower rib margin and the iliac crest 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 the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Waist Circumference Measured According to the JASSO (Japan Society for the Study of Obesity) Guideline	Change in Waist circumference measured according to the JASSO guideline 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 the start of randomisation to last trial-related subject-site contact.	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 the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Body Mass Index (BMI)	Change in BMI 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 the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Visceral Fat Area (VFA) (%)	Change in VFA 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 the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Visceral Fat Area (VFA) Centimeter Square (cm^2)	Change in VFA 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 the start of randomisation to last trial-related subject-site contact.	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 the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in HbA1c (mmol/Mol)	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 the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Fasting Plasma Glucose	Change in fasting plasma glucose from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Fasting Serum Insulin-ratio to Baseline	Change in fasting serum insulin measured as milli-international units per milliliter (mIU/mL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.	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 the start of randomisation to last trial-related subject-site contact.	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 the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Total Cholesterol-ratio to Baseline	Change in total cholesterol measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in High-density Lipoproteins (HDL)-Ratio to Baseline	Change in HDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Low-density Lipoproteins (LDL)-Ratio to Baseline	Change in LDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Very Low-density Lipoproteins (VLDL)-Ratio to Baseline	Change in VLDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Free Fatty Acids-ratio to Baseline	Change in free fatty acids measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Triglycerides-ratio to Baseline	Change in triglycerides measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline	Change in hsCRP measured in milligram per ilitre (mg/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Plasminogen Activator Inhibitor-1 Activity-ratio to Baseline	Change in plasminogen activator inhibitor-1 (PAI-1) activity measured in arbritary units per milliliter (AU/ml) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.	Baseline (week 0) to week 68
Secondary	Change in Short Form 36 v2.0 Acute (SF-36) Score	SF-36 is a 36-item patient-reported survey of patient health that measures participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured eight domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for all the domains. The 0-100 scale scores from SF-36 were converted to norm-based scores to enable a direct interpretation in relation to distribution of scores in the 2009 U.S. general population. In metric of norm-based scores, 50 and 10 corresponds to mean and standard deviation respectively. Change from week 0 in 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 data from in-trial observation period which is uninterrupted time interval from randomisation to last contact with trial site.	Baseline (week 0) to week 68
Secondary	Change in Impact of Weight on Quality of Life-lite for Clinical Trials (IWQOL-Lite for CT) Score	The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for 'physical function score' physical and psychosocial domains, and for total'. The endpoint was evaluated based on the data from in-trial observation period which is the uninterrupted time interval from randomisation to last contact with trial site.	Baseline (week 0) to week 68
Secondary	Number of Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score	The number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on 3.7 threshold. 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 the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on in-trial observation period which is the uninterrupted time interval from randomisation to last contact with trial site.	At week 68
Secondary	Number of Participants Who Achieve (Yes/no): Responder Definition Value for IWQoL-Lite for CT Physical Function (5-items) Score	The number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 68 weeks was determined based on thresholds of 14.6. The threshold of 14.6 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on FDA recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers the number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on in-trial observation period which is the uninterrupted time interval from randomisation to last contact with trial site.	At week 68
Secondary	Number of Participants Who Achieved (Yes/no): HbA1c <7.0% (53 mmol/Mol)	Number of participants who achieved HbA1c <7% (53 mmol/mol) at week 68 is presented. In the reported data, "Yes" infers the number of participants who have achieved HbA1c values less than the 7% and "No" infers the number of participants who have not achieved HbA1c values less than the 7%. The endpoint was evaluated based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.	At week 68
Secondary	Number of Participants Who Achieved (Yes/no): HbA1c =6.5% (48 mmol/Mol)	Number of participants who achieved HbA1c =6.5% (48 mmol/mol) at week 68 is presented. In the reported data, "Yes" infers the number of participants who have achieved HbA1c values less than or equal to 6.5% and "No" infers the number of participants who have not achieved HbA1c values less than or equal to 6.5%. The endpoint was evaluated based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.	At week 68
Secondary	Number of Treatment-emergent 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 with onset during the on-treatment observation period. On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.	Week 0 to week 75
Secondary	Number of Serious Adverse Events	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. SAE results occurred from week 0 to week 75 is presented based on the on-treatment observation, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.	Week 0 to week 75
Secondary	Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemia Episodes	Hypoglycaemic episodes with onset during on-treatment observation period were considered treatment-emergent. Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemia episodes with onset during on-treatment observation period were presented. Severe hypoglycaemia: episode requiring assistance of another person to administer carbohydrate, glucagon or take other corrective actions. plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by low PG concentration. BG confirmed symptomatic hypoglycaemia: episode that is BG confirmed by PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. On-treatment observation period is interval from date of first trial product administration (week 0) to date of last trial product administration (week 68) plus 7-week follow-up period and excluding any off-treatment time intervals.	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, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.	Baseline (week 0) to week 68
Secondary	Change in Amylase: Ratio to Baseline	Change in amylase measured in units/liter (U/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.	Baseline (week 0) to week 68
Secondary	Change in Lipase: Ratio to Baseline	Change in lipase measured in units/litre (U/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.	Baseline (week 0) to week 68
Secondary	Change in Calcitonin: Ratio to Baseline	Change in calcitonin measured in nanogram/litre (ng/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.	Baseline (week 0) to week 68
Secondary	Change in QTCF Interval	Change in QTCF Interval from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.	Baseline (week 0) to week 68