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Trial · Interventional

CompletedPhase 3Results postedRegistry data

Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity

Short name STEP 4

NCTNCT03548987 (opens ClinicalTrials.gov in a new tab)Other idNN9536-4376Other idU1111-1201-0898Other id2017-003473-34Other id2017
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
902 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Quadruple masking
Countries
10 countries

United States, Denmark, Israel, Netherlands, Portugal, South Africa, Spain, Sweden, Switzerland, Ukraine

Start
4 Jun 2018
Primary completion
22 Feb 2020
Completion
20 Mar 2020
First posted
7 Jun 2018
Last update posted
19 Jan 2022
Conditions
Metabolism and Nutrition Disorder · Obesity

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2018201920202021
  1. Ph 3

    STEP 4

    NCT03548987

    4 Jun 2018 to 20 Mar 2020

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • SemaglutideDrug
  • PlaceboDrug

Arms2

  • Experimental

    Semaglutide

    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.

  • Placebo comparator

    Placebo

    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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change From Randomisation to Week 68 in Body Weight (%)

    Time frame · Randomisation (week 20) to week 68

    Registry description

    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).

Secondary outcomes(20)

  1. Change in Waist Circumference

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  2. Change in Systolic Blood Pressure

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  3. Change in Diastolic Blood Pressure

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  4. Change in Physical Functioning Score (Short Form 36 [SF-36])

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  5. Change in Body Weight [Kilogram (Kg)]

    Time frame · Randomisation (week 20) to week 68

    Registry description

    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).

  6. Change in Body Mass Index (BMI)

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  7. Change in Haemoglobin A1c (HbA1c) [%]

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  8. Change in HbA1c [Millimoles Per Mole (mmol/Mol)]

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  9. Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)]

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  10. Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)]

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  11. Change in Fasting Serum Insulin

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  12. Change in Total Cholesterol

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  13. Change in High-density Lipoproteins (HDL)

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  14. Change in Low-density Lipoproteins (LDL)

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  15. Change in Very Low-density Lipoproteins (VLDL)

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  16. Change in Free Fatty Acids

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  17. Change in Triglycerides

    Time frame · Randomization (week 20) to week 68

    Registry description

    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).

  18. Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score

    Time frame · Randomisation (week 20) to week 68

    Registry description

    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).

  19. Subjects Who Gain Weight (Yes/no)

    Time frame · Randomisation (week 20) to week 68

    Registry description

    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).

  20. Change in Body Weight

    Time frame · Run-in (week 0) to week 68

    Registry description

    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).

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Randomisation (week 20) to week 68

Change From Randomisation to Week 68 in Body Weight (%)

GroupValue (Percentage point)Spread
Semaglutide 2.4 mg-8.38.1
Placebo6.57.7
Secondary and other outcome results(7)
Secondary outcomeMean· Randomization (week 20) to week 68

Change in Waist Circumference

GroupValue (Centimeter (cm))Spread
Semaglutide 2.4 mg-6.97.5
Placebo3.27.0
Secondary outcomeMean· Randomization (week 20) to week 68

Change in Systolic Blood Pressure

GroupValue (Millimeters of mercury (mmHg))Spread
Semaglutide 2.4 mg014
Placebo513
Secondary outcomeMean· Randomization (week 20) to week 68

Change in Diastolic Blood Pressure

GroupValue (mmHg)Spread
Semaglutide 2.4 mg09
Placebo19
Secondary outcomeMean· Randomization (week 20) to week 68

Change in Physical Functioning Score (Short Form 36 [SF-36])

GroupValue (Scores on a scale)Spread
Semaglutide 2.4 mg1.03.8
Placebo-1.24.5
Secondary outcomeMean· Randomisation (week 20) to week 68

Change in Body Weight [Kilogram (Kg)]

GroupValue (Kg)Spread
Semaglutide 2.4 mg-7.57.6
Placebo5.76.7
Secondary outcomeMean· Randomization (week 20) to week 68

Change in Body Mass Index (BMI)

GroupValue (Kilogram per square meter (kg/sqm))Spread
Semaglutide 2.4 mg-2.72.7
Placebo2.02.4
Secondary outcomeMean· Randomization (week 20) to week 68

Change in Haemoglobin A1c (HbA1c) [%]

GroupValue (Percentage point of HbA1c)Spread
Semaglutide 2.4 mg-0.20.3
Placebo0.10.2

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Semaglutide: Run-in PeriodParticipants were to receive once-weekly s.c injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL in run-in period (week 0 to week 20) with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached.0 / 90221 / 902670 / 902
Semaglutide 2.4: Treatment PeriodParticipants were to receive once-weekly s.c injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20. Thus, out of 803, 535 participants were continued to receive once weekly semaglutide s.c 2.4 mg until week 68.1 / 53541 / 535295 / 535
Placebo: Treatment PeriodParticipants were to receive once-weekly s.c injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20. Thus, out of 803, 268 participants were switched to receive once weekly placebo until week 68.1 / 26815 / 268114 / 268

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies7

Studies that cite this trial.

Studies with results

3 studies on this page

Indexing hint: Randomized controlled trial · 2023

5 results

Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity.

Wilkinson et al. 2023Obesity (Silver Spring, Md.)cited by 17

PMID 37605636DOI 10.1002/oby.23842PUB-37605636

Full text at the publisher5 results
Publisher pageSee results (5)

Indexing hint: Randomized controlled trial · 2021

6 results

Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.

Rubino et al. 2021JAMAcited by 1,095

PMID 33755728PMC7988425DOI 10.1001/jama.2021.3224PUB-33755728

Rights unknown6 results
Source linkSee results (6)

Indexing hint: Randomized controlled trial · 2020

Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5.

Kushner et al. 2020Obesity (Silver Spring, Md.)cited by 209

PMID 32441473PMC7318657DOI 10.1002/oby.22794PUB-32441473

Free to read · publisher termsCC BY-NC
Read at source

Indexing hint: Randomized controlled trial · 2018

10 results

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.

O'Neil et al. 2018Lancet (London, England)cited by 615

PMID 30122305DOI 10.1016/s0140-6736(18)31773-2PUB-30122305

Full text at the publisher10 results
Publisher pageSee results (10)

More studies

3 studies on this page

Indexing hint: Randomized controlled trial · 2024

Corrected

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.

Rubino et al. 2024Diabetes, obesity & metabolismcited by 38

PMID 38698650DOI 10.1111/dom.15620PUB-38698650

Full text at the publisher
Publisher pageRead the notice

PubMed tag: none · 2023

Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses.

Kosiborod et al. 2023Diabetes, obesity & metabolismcited by 98

PMID 36200477PMC10092593DOI 10.1111/dom.14890PUB-36200477

Free to read · publisher termsCC BY-NC
Read at source

PubMed tag: none · 2022

Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program.

Perreault et al. 2022Diabetes carecited by 61

PMID 35724304PMC9862484DOI 10.2337/dc21-1785PUB-35724304

Rights unknown
Source link

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * 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 Exclusion Criteria: * 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

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