Clinical trial NCT03548935: STEP 1: Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity
Official title: Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metabolism and Nutrition Disorder
Overweight or Obesity
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2018-06-07
Enrollment: 1961
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will look at the change in participants' body weight from the start to the end of the study. The weight loss in participants taking semaglutide (a new medicine) will be compared to the weight loss of participants 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 you can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment participants get, is decided by chance. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. The study has two phases: A main phase and an extension phase.The main phase will last for about 1.5 years. Participants will have 15 clinic visits and 10 phone calls with the study doctor. Extension phase: Approximately 300 participants will continue in the extension phase in the following countries only: Canada, Germany, the UK and selected sites in the US and Japan. These participants will be in the study for about 2.5 years.They will not receive treatment, but will attend another 5 follow-up visits with the study doctor.


Eligibility criteria: Inclusion Criteria:

Main phase:

* 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 30.0 kg/sqm or greater than or equal to 27.0 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

Extension phase:

* Informed consent for the extension phase obtained before any trial related activities for the extension phase
* On randomised treatment on the target dose at week 68, i.e. treated with 2.4 mg semaglutide once-weekly or semaglutide placebo

Exclusion Criteria:

Main phase:

* Glycated haemoglobin (HbA1C) greater than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening
* A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Extension phase:

* Female who is pregnant or intends to become pregnant during the extension phase
* Any disorder, unwillingness or inability, not covered by any of the other exclusion criteria, which in the investigator's opinion, might jeopardise the subject's compliance with the extension of the trial

Primary outcomes:
measure: Change in Body Weight (%)
timeFrame: Baseline (week 0) to week 68
measure: Participants Who Achieve 5 or More Percent Body Weight Reduction (Yes/no)
timeFrame: After week 68
Secondary outcomes:
measure: Subjects Who Achieve 10 or More Percent Body Weight Reduction (Yes/no)
timeFrame: Week 68
measure: Participants Who Achieve 15 or More Percent Body Weight Reduction (Yes/no)
timeFrame: Week 68
measure: Participants Who Achieve 20 or More Percent Body Weight Reduction (Yes/no)
timeFrame: Week 68
measure: Change in Waist Circumference (cm)
timeFrame: Baseline (week 0) to week 68
measure: Change in Systolic Blood Pressure (mmHg)
timeFrame: Baseline (week 0) to week 68
measure: Change in Short Form 36 (SF-36)
timeFrame: Baseline (week 0) to week 68
measure: Change in Impact of Weight on Quality of Life-Lite for Clinical Trial (IWQoL-Lite for CT) Score
timeFrame: Baseline (week 0) to week 68
measure: Change in Body Weight (kg)
timeFrame: Baseline (week 0) to week 68
measure: Change in Body Mass Index (BMI) (kg/m2)
timeFrame: Baseline (week 0) to week 68
measure: Change in HbA1C (%)
timeFrame: Baseline (week 0) to week 68
measure: Change in HbA1C (mmol/Mol)
timeFrame: Baseline (week 0) to week 68
measure: Change in Fasting Plasma Glucose (FPG) (mg/dL)
timeFrame: Baseline (week 0) to week 68
measure: Change in Fasting Serum Insulin (mIU/L) - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in Diastolic Blood Pressure (mmHg)
timeFrame: Baseline (week 0) to week 68
measure: Change in Total Cholesterol (mg/dL) - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in High-density Lipoproteins (HDL) (mg/dL) - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in Low-density Lipoproteins (LDL) (mg/dL) - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in Very Low-density Lipoproteins (VLDL) (mg/dL) - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in Free Fatty Acids (mg/dL) - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in Triglycerides (mg/dL) - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in High Sensitivity C-Reactive Protein (hsCRP) - (mg/L) - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in Plasminogen Activator Inhibitor-1 (PAI-1) Activity (AU/ml) - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in Soluble Leptin Receptor (ng/mL) - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in Leptin (ng/mL) - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in Body Composition (Total Fat Mass) (%)
timeFrame: Baseline (week 0) to week 68
measure: Change in Body Composition (Total Fat Mass) (kg)
timeFrame: Baseline (week 0) to week 68
measure: Change in Body Composition (Lean Body Mass) (%)
timeFrame: Baseline (week 0) to week 68
measure: Change in Body Composition (Lean Body Mass) (kg)
timeFrame: Baseline (week 0) to week 68
measure: Change in Body Composition (Visceral Fat Mass) (%)
timeFrame: Baseline (week 0) to week 68
measure: Change in Body Composition (Visceral Fat Mass) (kg)
timeFrame: Baseline (week 0) to week 68
measure: Change in Body Weight (%) - DEXA Subpopulation
timeFrame: Baseline (week 0) to week 68
measure: Change in Body Weight (kg) - DEXA Subpopulation
timeFrame: Baseline (week 0) to week 68
measure: Participants Who Achieve "Responder Definition Value" (Yes/no) for SF-36 Physical Functioning Score
timeFrame: After week 68
measure: Participants Who Achieve "Responder Definition Value" (Yes/no) for IWQoL-Lite for CT Physical Function Domain (5-items) Score
timeFrame: After week 68
measure: Number of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline (week 0) to week 75
measure: Number of Serious Adverse Events (SAEs)
timeFrame: Baseline (week 0) to week 75
measure: Change in Pulse
timeFrame: Baseline (week 0) to week 68
measure: Change in Amylase - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in Lipase - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
measure: Change in Calcitonin - Ratio to Baseline
timeFrame: Baseline (week 0) to week 68
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Anaheim
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Lomita
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Spring Valley
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Aurora
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Waterbury
country: United States
facility: Novo Nordisk Investigational Site
state: Connecticut
city: Chiefland
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Crystal River
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Ocala
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Panama City
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Plantation
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Ponte Vedra
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Roswell
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Topeka
country: United States
facility: Novo Nordisk Investigational Site
state: Kansas
city: Louisville
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Buckley
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Saint Peters
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: Butte
country: United States
facility: Novo Nordisk Investigational Site
state: Montana
city: Omaha
country: United States
facility: Novo Nordisk Investigational Site
state: Nebraska
city: Rochester
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Salisbury
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: West Reading
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Simpsonville
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Nashville
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Round Rock
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Bountiful
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Richmond
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Renton
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Ciudad de Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Corrientes
country: Argentina
facility: Novo Nordisk Investigational Site
city: Córdoba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Santa Rosa
country: Argentina
facility: Novo Nordisk Investigational Site
city: Boussu
country: Belgium
facility: Novo Nordisk Investigational Site
city: Bruxelles
country: Belgium
facility: Novo Nordisk Investigational Site
city: Edegem
country: Belgium
facility: Novo Nordisk Investigational Site
city: Leuven
country: Belgium
facility: Novo Nordisk Investigational Site
city: Liège
country: Belgium
facility: Novo Nordisk Investigational Site
city: Plovdiv
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Edmonton
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Surrey
country: Canada
facility: Novo Nordisk Investigational Site
state: British Columbia
city: Hamilton
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: North York
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Quebec
country: Canada
facility: Novo Nordisk Investigational Site
city: Quebec
country: Canada
facility: Novo Nordisk Investigational Site
city: Aarhus N
country: Denmark
facility: Novo Nordisk Investigational Site
city: Oulu
country: Finland
facility: Novo Nordisk Investigational Site
city: University Of Helsinki
country: Finland
facility: Novo Nordisk Investigational Site
city: Le Coudray
country: France
facility: Novo Nordisk Investigational Site
city: Narbonne
country: France
facility: Novo Nordisk Investigational Site
city: PARIS cedex 13
country: France
facility: Novo Nordisk Investigational Site
city: Paris
country: France
facility: Novo Nordisk Investigational Site
city: Pessac
country: France
facility: Novo Nordisk Investigational Site
city: Pierre Benite
country: France
facility: Novo Nordisk Investigational Site
city: Venissieux
country: France
facility: Novo Nordisk Investigational Site
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
city: Bochum
country: Germany
facility: Novo Nordisk Investigational Site
city: Essen
country: Germany
facility: Novo Nordisk Investigational Site
city: Essen
country: Germany
facility: Novo Nordisk Investigational Site
city: Falkensee
country: Germany
facility: Novo Nordisk Investigational Site
city: Frankfurt
country: Germany
facility: Novo Nordisk Investigational Site
city: Giessen
country: Germany
facility: Novo Nordisk Investigational Site
city: Hamburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Hohenmölsen
country: Germany
facility: Novo Nordisk Investigational Site
city: Leipzig
country: Germany
facility: Novo Nordisk Investigational Site
city: Saint Ingbert-Oberwürzbach
country: Germany
facility: Novo Nordisk Investigational Site
city: Stuttgart
country: Germany
facility: Novo Nordisk Investigational Site
city: Wangen
country: Germany
facility: Novo Nordisk Investigational Site
city: Guntur
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Secunderabad,
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Surat
country: India
facility: Novo Nordisk Investigational Site
state: Gujarat
city: Rohtak
country: India
facility: Novo Nordisk Investigational Site
state: Haryana
city: Thiruvananthapuram
country: India
facility: Novo Nordisk Investigational Site
state: Kerala
city: Nagpur
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Pune
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Pune
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: New Dehli
country: India
facility: Novo Nordisk Investigational Site
state: New Delhi
city: Chennai
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Kolkata
country: India
facility: Novo Nordisk Investigational Site
state: West Bengal
city: Hyderabad
country: India
facility: Novo Nordisk Investigational Site
city: Ludhiana
country: India
facility: Novo Nordisk Investigational Site
city: Chiba-shi, Chiba
country: Japan
facility: Novo Nordisk Investigational Site
city: Suita-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Guadalajara
country: Mexico
facility: Novo Nordisk Investigational Site
state: Jalisco
city: Hermosillo
country: Mexico
facility: Novo Nordisk Investigational Site
state: Sonora
city: Merida
country: Mexico
facility: Novo Nordisk Investigational Site
state: Yucatan
city: Gdynia
country: Poland
facility: Novo Nordisk Investigational Site
city: Lodz
country: Poland
facility: Novo Nordisk Investigational Site
city: Poznan
country: Poland
facility: Novo Nordisk Investigational Site
city: Szczecin
country: Poland
facility: Novo Nordisk Investigational Site
city: San Juan
country: Puerto Rico
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Penza
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Tomsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Voronezh
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Yaroslavl
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Taipei
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Bristol
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Cambridge
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Coventry
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Glasgow
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Liverpool
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Norwich
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Rotherham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Taunton
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.
citation: Kosiborod 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.
citation: Perreault 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.
citation: Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Rosenstock J, Wadden TA, Wharton S, Yokote K, Kushner RF; STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564. doi: 10.1111/dom.14725. Epub 2022 May 19.
citation: 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.