Research Study Investigating How Well Semaglutide Works in People With Type 2 Diabetes Suffering From Overweight or Obesity (STEP 2)

• ClinicalTrials.gov Identifier: NCT03552757
• Recruitment Status: Active, not recruiting
• First Posted: June 12, 2018
• Last Update Posted: May 10, 2019
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: May 30, 2018
• First Posted Date: June 12, 2018
• Last Update Posted Date: May 10, 2019
• Actual Study Start Date: June 4, 2018
• Estimated Primary Completion Date: March 16, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 30, 2018)

• Change in body weight [ Time Frame: Week 0, week 68 ]
  Measured in %
• Subjects who achieve (yes/no): Body weight reduction greater than or equal to 5% [ Time Frame: Week 0, week 68 ]
  Number of subjects

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03552757 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: May 30, 2018)

• Subjects who achieve (yes/no): Body weight reduction greater than or equal to 10% [ Time Frame: Week 0, week 68 ]
  Number of subjects
• Subjects who achieve (yes/no): Body weight reduction greater than or equal to 15% [ Time Frame: Week 0, week 68 ]
  Number of subjects
• Change in waist circumference [ Time Frame: Week 0, week 68 ]
  Measured in centimetre
• Change in body weight (%) (semaglutide s.c. 2.4 mg once-weekly versus semaglutide s.c. 1.0 mg once-weekly) [ Time Frame: Week 0, week 68 ]
  Measured in %
• Change in haemoglobin A1c (HbA1c) [ Time Frame: Week 0, week 68 ]
  Measured in %
• Change in HbA1c [ Time Frame: Week 0, week 68 ]
  Measured in mmol/mol
• Change in systolic blood pressure [ Time Frame: Week 0, week 68 ]
  Measured in mmHg
• Change in physical functioning score (short form-36 [SF-36]) [ Time Frame: Week 0, week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health
• Change in physical function domain (5-items) score (Impact of weight on quality of Life-lite [IWQoL-Lite] for Clinical Trials [CT]) [ Time Frame: Week 0, week 68 ]
  The IWQoL-Lite for CT is a 20-item modified version of a questionnaire tool designed to assess the weight-related quality of life.
• Change in body weight [ Time Frame: Week 0, week 68 ]
  Measured in kg
• Change in body mass index (BMI) [ Time Frame: Week 0, week 68 ]
  Measured in kg/m^2
• Change in HbA1c (semaglutide s.c. 1.0 mg once-weekly versus semaglutide placebo I/II) [ Time Frame: Week 0, week 68 ]
  Measured in %
• Change in HbA1c (semaglutide s.c. 1.0 mg once-weekly versus semaglutide placebo I/II) [ Time Frame: Week 0, week 68 ]
  Measured in mmol/mol
• Change in fasting plasma glucose (FPG) [ Time Frame: Week 0, week 68 ]
  Measured in mg/dL
• Change in fasting serum insulin [ Time Frame: Week 0, week 68 ]
  Measured in mIU/L
• Change in diastolic blood pressure [ Time Frame: Week 0, week 68 ]
  Measured in mmHg
• Change in total cholesterol [ Time Frame: Week 0, week 68 ]
  Measured in mg/dL
• Change in high density lipoprotein (HDL) cholesterol [ Time Frame: Week 0, week 68 ]
  Measured in mg/dL
• Change in low density lipoprotein (LDL) cholesterol [ Time Frame: Week 0, week 68 ]
  Measured in mg/dL
• Change in very low density lipoprotein (VLDL) cholesterol [ Time Frame: Week 0, week 68 ]
  Measured in mg/dL
• Change in free fatty acids [ Time Frame: Week 0, week 68 ]
  Measured in mg/dL
• Change in triglycerides [ Time Frame: Week 0, week 68 ]
  Measured in mg/dL
• Change in high sensitivity C-Reactive Protein [ Time Frame: Week 0, week 68 ]
  Measured in mg/L
• Change in Plasminogen Activator Inhibitor-1 (PAI-1) Activity [ Time Frame: Week 0, week 68 ]
  Measured in AU/mL
• Change in SF-36 (role-physical score) [ Time Frame: Week 0, week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health
• Change in SF-36 (bodily pain score) [ Time Frame: Week 0, week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health
• Change in SF-36 (general health score) [ Time Frame: Week 0, week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health
• Change in SF-36 (vitality score) [ Time Frame: Week 0, week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health
• Change in SF-36 (social functioning score) [ Time Frame: Week 0, week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health
• Change in SF-36 (role-emotional score) [ Time Frame: Week 0, week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health
• Change in SF-36 (mental health score) [ Time Frame: Week 0, week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health
• Change in SF-36 (physical component summary) [ Time Frame: Week 0, week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health
• Change in SF-36 (mental component summary) [ Time Frame: Week 0, week 68 ]
  Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health
• Change in IWQoL-Lite for CT (pain/discomfort domain score) [ Time Frame: Week 0, week 68 ]
  The IWQoL-Lite for CT is a 20-item modified version of a questionnaire tool designed to assess the weight-related quality of life.
• Change in IWQoL-Lite for CT (psychosocial domain score) [ Time Frame: Week 0, week 68 ]
  The IWQoL-Lite for CT is a 20-item modified version of a questionnaire tool designed to assess the weight-related quality of life.
• Change in IWQoL-Lite for CT (total score) [ Time Frame: Week 0, week 68 ]
  The IWQoL-Lite for CT is a 20-item modified version of a questionnaire tool designed to assess the weight-related quality of life.
• Subjects who achieve (yes/no): Responder definition value for SF-36 physical functioning score [ Time Frame: week 0, week 68 ]
  Number of subjects
• Subjects who achieve (yes/no): Responder definition value for IWQoL-Lite for CT physical function domain (5-items) score [ Time Frame: Week 0, week 68 ]
  Number of subjects
• Subjects who achieve (yes/no): HbA1c less than 7.0% (53 mmol/mol) [ Time Frame: Week 0, week 68 ]
  Number of subjects
• Subjects who achieve (yes/no): HbA1c less than or equal to 6.5% (48 mmol/mol) [ Time Frame: Week 0, week 68 ]
  Number of subjects
• Number of treatment-emergent adverse events (TEAEs) [ Time Frame: From week 0 to week 75 ]
  Number of events
• Number of serious adverse events (SAEs) [ Time Frame: From week 0 to week 75 ]
  Number of events
• Number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemia episodes [ Time Frame: From week 0 to week 75 ]
  Number of events
• Change in pulse [ Time Frame: Week 0, week 68 ]
  measured in beats per minute
• Change in amylase [ Time Frame: Week 0, week 68 ]
  measured in U/L
• Change in lipase [ Time Frame: Week 0, week 68 ]
  measured in U/L
• Change in calcitonin [ Time Frame: Week 0, week 68 ]
  measured in ng/L

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Research Study Investigating How Well Semaglutide Works in People With Type 2 Diabetes Suffering From Overweight or Obesity
• Official Title: Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity and Type 2 Diabetes
• Brief Summary: This study will look at the change in the 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 study medicine, the participant will have talks with study staff about healthy food choices, how to be more physically active and what else the participant can do to lose weight. Overweight and obesity is associated with an increased risk of type 2 diabetes. Therefore, weight loss has shown to have a beneficial impact on the blood sugar levels. The participant will either get semaglutide or "dummy" medicine - which treatment the participant get is decided by chance. The participant will need to take 2 injections at the same time 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Obesity
• Overweight

Intervention

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

Study Arms

• Experimental: Semaglutide 1.0 mg
  Participants will receive semaglutide 1.0 mg and semaglutide placebo I during 68-week treatment period in addition to a reduced-calorie diet and increased physical activity.
  Interventions:

  • Drug: Semaglutide 1.0 mg
  • Drug: Placebo I (Semaglutide)
• Experimental: Semaglutide 2.4 mg
  Participants will receive semaglutide 2.4 mg and semaglutide placebo II during 68-week treatment period in addition to a reduced-calorie diet and increased physical activity.
  Interventions:

  • Drug: Semaglutide 2.4 mg
  • Drug: Placebo II (Semaglutide)
• Placebo Comparator: Semaglutide placebo I/II
  Participants will receive semaglutide placebo I and II during 68-week treatment period in addition to a reduced-calorie diet and increased physical activity.
  Interventions:

  • Drug: Placebo I (Semaglutide)
  • Drug: Placebo II (Semaglutide)

• Publications *: O'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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 9, 2019): 1210
• Original Estimated Enrollment (submitted: May 30, 2018): 1200
• Estimated Study Completion Date: May 4, 2020
• Estimated Primary Completion Date: March 16, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female, age greater than or equal to 18 years at the time of signing informed consent
• Body Mass Index (BMI) greater than or equal to 27 kg/m^2 '
• History of at least one self-reported unsuccessful dietary effort to lose body weight
• Diagnosed with type 2 diabetes (haemoglobin A1c 7-10% (53-86 mmol/mol) (both inclusive)) 180 days or longer prior to the day of screening

Exclusion Criteria:

• A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records
• 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 Cotransporter 2 Inhibitors) according to chronic kidney disease (CKD)-Epidemiology Collaboration (EPI) creatinine equation as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 by the central laboratory at screening
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (e.g. optometrist) within the past 90 days prior to screening or in the period between screening and randomisation

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Algeria, Argentina, Canada, Germany, Greece, India, Japan, Puerto Rico, Russian Federation, South Africa, Spain, United Arab Emirates, United Kingdom, United States

Administrative Information

• NCT Number: NCT03552757
• Other Study ID Numbers: NN9536-4374; U1111-1200-8148 ( Other Identifier: World Health Organization (WHO) ); 2017-003414-10 ( Other Identifier: European Medicines Agency (EudraCT) )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://www.novonordisk-trials.com

• Responsible Party: Novo Nordisk A/S
• Study Sponsor: Novo Nordisk A/S
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452); Novo Nordisk A/S

• PRS Account: Novo Nordisk A/S
• Verification Date: May 2019