Research Study Looking at How Well Semaglutide Works in People Suffering From Obesity and Knee Osteoarthritis

Effect of Subcutaneous Semaglutide 2.4 mg Once-weekly Compared to Placebo in Subjects With Obesity and Knee Osteoarthritis

This study will look at participants body weight from the start to the end of the study. It will also look at how much pain participants have in participants knee from the start to the end of the study and how this affects participants daily life. This is to compare the effect on body weight and pain in the knee in people taking semaglutide with people taking "dummy" medicine. 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. During the study, participants will have talks with study staff about how to eat healthy food and how to be more physically active. The study will last for about 1 ½ years. Participants will have 14 clinic visits with the study staff. At the first clinic visit participants will have a blood sample taken. Participants will have an X-ray of participants knee taken at the first visit. If participants have had an X-ray recently, this may not be needed.

At 6 of the clinic visits participants cannot take pain medications for 3 days before the visit. Participants cannot take part if participants have had a joint replacement surgery in participants knee. Participants cannot take part if participants have or have had diabetes. Women: Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: semaglutide 2.4 mg; Drug: semaglutide 2.4 mg (placebo)

• Study Type: Interventional
• Enrollment (Actual): 407
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4G5
    • Institut universitaire de cardiologie
  • Toronto, Canada, M5V 3L9
    • Master Centre for Canada
  • Alberta
    • Calgary, Alberta, Canada, T2V 4J2
      • C-endo Diab Endo Clin Calgery
    • Edmonton, Alberta, Canada, T6H 2L4
      • C-endo Diab & Endo Clinic
  • British Columbia
    • Surrey, British Columbia, Canada, V3Z 2N6
      • Ocean West Research Clinic
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G 1A7
      • G.A. Research Associates Ltd.
  • Newfoundland and Labrador
    • Mount Pearl, Newfoundland and Labrador, Canada, A1N 1W7
      • Commonwealth Medical Clinic
  • Ontario
    • Burlington, Ontario, Canada, L7M 4Y1
      • Manna Research Inc. (Burlington N)
    • Hamilton, Ontario, Canada, L8L 5G8
      • Wharton Med Clin Trials
    • Hamilton, Ontario, Canada, L8M 1K7
      • Premier Clinical Trial Research Network (PCTRN)
    • London, Ontario, Canada, N5W 6A2
      • Milestone Research
    • Toronto, Ontario, Canada, M9W 4L6
      • Manna Research Inc._Toronto
    • Toronto, Ontario, Canada, M9V 4B4
      • Dr Anil K Gupta Med Prof Corp
  • Quebec
    • Montreal, Quebec, Canada, H4N 2W2
      • Centre Medical Acadie
    • Québec, Quebec, Canada, G1J 1Z4
      • CHU de Quebec-Universite Laval
    • Saint-Marc-des-Carrieres, Quebec, Canada, G0A 4B0
      • Ctr Méd. et pro d l'Ost d port
• Colombia
  • Barranquilla, Colombia, 80020
    • Centro de Investigacion Medico Asistencial S.A.S
  • Bogotá, Colombia, 110221
    • CentrodeInvestigaciónenReumatologíayEspecialidadesMédicas
  • Bogotá, Colombia, 110221
    • BLUECARE SALUD S.A.S. Sede Centro Médico Integral
  • Chía, Colombia, 250001
    • Preventive Care S.A.S
• Denmark
  • Aarhus N, Denmark, 8200
    • Klinik for Led og bindevævssygdomme
  • Frederiksberg, Denmark, 2000
    • Frederiksberg Hospital - Parker Institutet (Artrose)
• France
  • Clermont-Ferrand, France, 63000
    • Centre Hospitalier de Clermont-Ferrand-Hopital Gabriel Montpied
  • Le Creusot, France, 71200
    • Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-2
  • Paris, France, 75651
    • CHU Pitié-Salpêtrière
  • Paris, France, 75908
    • Hôpital Européen Georges Pompidou
  • Paris, France, 75908
    • Ap-Hp-Hopital Europeen Georges Pompidou
  • Paris, France, 75651
    • Aphp-Hopital La Pitie Salpetriere-3
  • Pierre-Bénite, France, 69310
    • Hospices Civils de Lyon-Hopital Lyon Sud-1
  • Toulouse, France, 31054
    • Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-2
  • Vénissieux, France, 69200
    • Centre de Recherche Clinique Portes Du Sud
• Norway
  • Nordbyhagen, Norway, 1474
    • Akershus Universitetssykehus
  • Oslo, Norway, 0586
    • Oslo us HF, Aker sykehus
  • Tønsberg, Norway, 3117
    • Senter for sykelig overvekt i Helse Sør-Øst
• Russia
  • Kazan', Russia, 420061
    • PIH "Clin Hosp "RZD-Medicina" former Kazan OJSC Rus Railways
  • Kemerovo, Russia, 650066
    • LLC Medical center "Maksimum Zdorovia"
  • Moscow, Russia, 119435
    • Setchenov First Moscow State Medical University
  • Moscow, Russia, 117292
    • FSBI 'I.I. Dedov National Medical Research Center of Endocrinology' of the MH of Russia
  • Moscow, Russia, 127486
    • Federal Bureau for Medical and Social Expertise
  • Saint Petersburg, Russia, 197110
    • Consultative & Diagnostic Center with a Outpatient Hospital
  • Saratov, Russia, 410002
    • SIH "Saratov Regional Clinical Hospital for War Veterans"
  • Tomsk, Russia, 634050
    • Siberian State Medical University
  • Voronezh, Russia, 394018
    • Voronezh Regional Clinical Consultive-diagnostic Centre
  • Yaroslavl, Russia, 150047
    • SBCI HC Yaroslavl region "Central City Hospital"
• Saudi Arabia
  • Al Ahsa, Saudi Arabia, 36428
    • King Abdulaziz Hospital-Al Ahsa-National Guard
  • Riyadh, Saudi Arabia, 12372
    • King Khaled University Hospital,King Saud Univ. Med. City
  • Riyadh, Saudi Arabia, 12713
    • King Faisal Specialist Hospital & Research Centre, Riyadh
  • Riyadh, Saudi Arabia, 21451
    • King Fahad Medical City
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6001
      • Phoenix Pharma
  • Gauteng
    • Boksburg, Gauteng, South Africa, 1466
      • Dr Wilhase's rooms
    • Johannesburg, Gauteng, South Africa, 2013
      • Chris Hani Baragwanath Hospital
    • Pretoria, Gauteng, South Africa, 0184
      • Botho ke Bontle Health Services
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4450
      • Dr J Reddy
    • Durban, KwaZulu-Natal, South Africa, 4901
      • Lenmed Shifa Private Hospital
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Seville, Spain, 41003
    • Clínica Nuevas Tecnologías en Diabetes y Endocrinología
• Sweden
  • Malmo, Sweden, 205 02
    • Forskningsmottagning Internmedicin (tidigare KFE)
  • Stockholm, Sweden, 112 81
    • S:t Göran Sjukhus
  • Stockholm, Sweden, 141 86
    • Department of Metabolism and Endocrinology
  • Örebro, Sweden, 701 85
    • Medicinkliniken Överviktsenheten USÖ
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36106
      • Baptist Health System
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Ortho Arizona
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • Beverly Hills, California, United States, 90211
      • Stuart L. Silverman MD - A Medical Corporation
    • Fresno, California, United States, 93720
      • Valley Research
    • Fullerton, California, United States, 92835
      • Providence Medical Foundation
    • Palm Springs, California, United States, 92262
      • Desert Oasis Hlthcr Med Group
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research_Spring Valley
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Florida
    • Hollywood, Florida, United States, 33024
      • Clinical Research of Hollywood_Hollywood
    • Jacksonville, Florida, United States, 32205
      • Westside Center For Clinical Research
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Ctr For Clin Res
    • Miami, Florida, United States, 33143
      • Well Pharma Medical Research Corp
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Plantation, Florida, United States, 33324
      • Clinical Trial Res Assoc,Inc
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East West Medical Research Institute_Honolulu
  • Illinois
    • Gurnee, Illinois, United States, 60031
      • Clinical Invest Special_Gurnee
    • Skokie, Illinois, United States, 60077
      • Evanston Premier Hlthcr Res
    • Wauconda, Illinois, United States, 60084
      • Clinical Invest Special_Gurnee
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical RC
    • Valparaiso, Indiana, United States, 46383
      • Velocity Clin. Res Valparaiso
  • Kansas
    • Shawnee Mission, Kansas, United States, 66217
      • KU MedWest
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Maryland Veterans Administration Health Care System
    • Elkridge, Maryland, United States, 21075-6437
      • Centennial Medical Group
  • Massachusetts
    • Boston, Massachusetts, United States, 02115-5804
      • Brigham & Women's Hospital
  • Michigan
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare, PLC.
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research LLC
    • Kansas City, Missouri, United States, 64114
      • The Center For Pharmaceutical Research PC
    • St Louis, Missouri, United States, 63141
      • Sundance Clinical Research LLC
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
    • New York, New York, United States, 10010
      • NYU Langone Medical Cent-Joan H Tisch Cnt for Women's Health
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
    • The Bronx, New York, United States, 10461
      • DaVita Clinical Research - New York
    • West Seneca, New York, United States, 14224
      • Southgate Medical Group, LLP
    • Westfield, New York, United States, 14787
      • Great Lakes Medical Research
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • University of North Carolina- Chapel Hill Adults
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest Life Sciences LLC
    • Greensboro, North Carolina, United States, 27405
      • Medication Mgmnt, LLC_Grnsboro
    • Raleigh, North Carolina, United States, 27609-7216
      • Raleigh Medical Group
    • Wilmington, North Carolina, United States, 28401
      • Accellacare
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Medical Research Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Velocity Clin Res_Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic_Cleveland
    • Cleveland, Ohio, United States, 44106-1702
      • Louis Stokes Clvlnd VA Med Ctr
    • Franklin, Ohio, United States, 45005
      • Prestige Clinical Research
    • Wadsworth, Ohio, United States, 44281
      • New Venture Medical Research
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635-8406
      • Altoona Osteoporosis Center
    • Philadelphia, Pennsylvania, United States, 19144
      • Parkside Family Medicine
    • Philadelphia, Pennsylvania, United States, 19104-3317
      • The University of Penn Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
      • Accellacare US Inc._SC
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Res Ctr.
    • Summerville, South Carolina, United States, 29485
      • Palmetto Clinical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37934
      • Tennova HC Turkey Creek MC
  • Texas
    • Houston, Texas, United States, 77024
      • PrimeCare Medical Group
    • Houston, Texas, United States, 77099
      • Southwest Houston Research Ltd
    • Tomball, Texas, United States, 77375
      • DM Clin Rsrch/Fam Diag Clinic
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Res of Hampton Roads
    • Richmond, Virginia, United States, 23294
      • National Clin Res Inc.
  • Washington
    • Olympia, Washington, United States, 98502
      • Capital Clin Res Ctr,LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female, age above or equal to 18 years at the time of signing informed consent
• Body Mass Index (BMI) equal to or greater than 30.0 kg/m^2
• Clinical diagnosis of knee OA (American College of Rheumatology (ACR) criteria) with moderate radiographic changes (Kellgren-Lawrence (KL) grades 2 or 3 as per central reading) in target knee. Target knee joint is defined as most symptomatic knee at screening. If pain in knees are equal target knee joint will be in the most dominant leg.
• Pain due to knee OA

Exclusion Criteria:

• Joint replacement in target knee
• Arthroscopy or injections into target knee within last 3 months prior to enrolment
• Any other joint disease in the target knee

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: semaglutide 2.4 mg; Participants will receive semaglutide subcutaneous (s.c) 2.4 mg once-weekly as adjunct to a reduced-calorie diet and increased physical activity	Drug: semaglutide 2.4 mg; semaglutide subcutaneous (s.c.) 2.4 mg once-weekly or semaglutide placebo once-weekly as adjunct to a reduced-calorie diet and increased physical activity
Placebo Comparator: semaglutide 2.4 mg (placebo); Participants will receive semaglutide subcutaneous (s.c) placebo once-weekly as adjunct to a reduced-calorie diet and increased physical activity	Drug: semaglutide 2.4 mg (placebo); semaglutide subcutanous (s.c.) 2.4 mg once-weekly or semaglutide placebo once-weekly as adjunct to a reduced-calorie diet and increased physical activity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Body Weight	Percentage change in body weight from baseline (week 0) to end of treatment (week 68) is presented. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	Baseline (week 0), end of treatment (week 68)
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score	WOMAC is a disease-specific patient-reported outcome measure designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with osteoarthritis of the hip and/or knee. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with osteoarthritis (OA). It consists of 3 subscales: pain, stiffness and physical function. The WOMAC raw pain score is derived as the sum of the 5 item scores in the pain domain. It will be normalised and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	Baseline (week 0), end of treatment (week 68)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Body Weight Reduction Greater Than or Equal to (≥) 5 Percent (%) (Yes/No)	Percentage of participants who achieved ≥ 5% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥5% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥5% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)
Percentage of Participants Achieving Body Weight Reduction ≥ 10% (Yes/No)	Percentage of participants who achieved ≥10% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥10% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥10% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)
Change in WOMAC Physical Function Score	Change in WOMAC physical function score is presented. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with osteoarthritis (OA). It consists of 3 subscales: pain, stiffness and physical function. WOMAC physical function is 17-item questionnaire used to assess degree of difficulty experienced due to OA in knee. It is calculated as the sum of the 17 item scores in the physical function domain. It is normalized and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the physical function domain (i.e. 170) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	Baseline (week 0), end of treatment (week 68)
Change in Short Form 36 (SF-36) Physical Functioning Score	SF-36 is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: physical component summary (including physical functioning, role-physical, bodily pain and general health) and mental component summary (including vitality, social functioning, role-emotional and mental health). Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.	Baseline (week 0), end of treatment (week 68)
Change in Waist Circumference	Change in waist circumference from baseline (week 0) to end of the treatment (visit 68) is presented. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	Baseline (week 0), end of treatment (week 68)
Change in WOMAC Stiffness Score	WOMAC is a disease-specific patient-reported outcome measure designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with osteoarthritis of the hip and/or knee. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with OA. It consists of 3 subscales: pain, stiffness and physical function. The WOMAC raw stiffness score is derived as the sum of the 2 item scores in the stiffness domain. It will be normalized and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the stiffness domain (i.e. 20) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	Baseline (week 0), end of treatment (week 68)
Change in WOMAC Total Score	WOMAC is a disease-specific patient-reported outcome measure designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with osteoarthritis of the hip and/or knee. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with OA. The WOMAC raw total score is derived as the sum of the 24 item scores respectively on pain, stiffness and physical function domain. It will be normalized and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the total domain (i.e. 240) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	Baseline (week 0), end of treatment (week 68)
Change in SF-36 Bodily Pain Score	Change in SF-36 Bodily Pain Score from baseline (week 0) to end of treatment (week 68) is presented. SF-36 is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: physical component summary and mental component summary. Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.	Baseline (week 0), end of treatment (week 68)
Change in SF-36 Physical Component Summary	Change in SF-36 physical component summary is presented. It is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: physical component summary and mental component summary. Physical component summary contains physical functioning, role-physical, bodily pain and general health. Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.	Baseline (week 0), end of treatment (week 68)
Change in SF-36 Mental Component Summary	Change in SF-36 mental component summary is presented. SF-36 is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: mental component summary and physical component summary. Mental component summary contain vitality, social functioning, role-emotional and mental health. Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.	Baseline (week 0), end of treatment (week 68)
Percentage of Participants Using Allowed Rescue Analgesics During Wash Out (Yes/No)	Percentage of participants using allowed rescue analgesics during wash out at end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have used allowed rescue analgesics during wash out whereas 'No' infers percentage of participants who have not used allowed rescue analgesics during wash out. Use of allowed rescue analgesics is evaluated based on use of acetaminophen reported in the pain medication diary from one up to 3 days prior to WOMAC assessment. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	At end of treatment (week 68)
Amount of Allowed Rescue Analgesics Used During Wash Out	Amount of allowed rescue analgesics used during wash out at end of treatment (week 68) is presented. Allowed rescue analgesic during washout is defined as acetaminophen taken 24-72 hour before the visit. The outcome measure is approximated by a total dose of acetaminophen reported in the pain medication diary from one and up to 3 days prior to WOMAC assessment. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	At end of treatment (week 68)
Percentage of Participants With Use of Pain Medication	Percentage of participants with use of pain medication from baseline (week 0) to end of treatment (week 68) is presented. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)
Change in Pain Intensity (Numerical Rating Scale [NRS])	Pain intensity was assessed on an 11-point NRS over the past 24 hours (before each specified visit), where a score of 0 indicated "no pain" and a score of 10 indicated "worst possible pain", where higher the score, greater the pain intensity. Response at visit was derived from the pain diary data as an average score over 4 days interval leading up to visit-related washout period for pain medication. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	Baseline (week 0), end of treatment (week 68)
Percentage of Participants Achieving Body Weight Reduction ≥ 15% (Yes/No)	Percentage of participants who achieved ≥15% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥15% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥15% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)
Percentage of Participants Achieving Body Weight Reduction ≥ 20% (Yes/No)	Percentage of participants who achieved ≥20% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥20% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥20% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)
Percentage of Participants Achieving WOMAC Pain Reduction ≥ 30% (Yes/No)	Percentage of participants who achieved ≥30% WOMAC pain reduction (yes/no) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥30% WOMAC pain reduction whereas 'No' infers percentage of participants who have not achieved ≥30% WOMAC pain reduction. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)
Percentage of Participants Achieving WOMAC Pain Reduction ≥ 50% (Yes/No)	Percentage of participants who achieved ≥50% WOMAC pain reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥50% WOMAC pain reduction whereas 'No' infers percentage of participants who have not achieved ≥50% WOMAC pain reduction. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)
Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Pain Score (Yes/No)	Percentage of participants who achieved threshold for clinically meaningful within-participant change in WOMAC pain score from baseline (week 0) to end of treatment (week 68) is presented. The threshold refers to the decrease of at least 37.3 in the WOMAC pain score and it is derived based on 1-category improvement on patient global impression of status (PGI-S) scale. In reported data, 'Yes' infers percentage of participants who have achieved threshold whereas 'No' infers percentage of participants who have not achieved threshold. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores=worse outcome. Outcome measure was evaluated based on data from in-trial period and it was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)
Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Physical Function Score (Yes/No)	Percentage of participants who achieved threshold for clinically meaningful within-participant change in WOMAC physical function score from baseline (week 0) to end of treatment (week 68) is presented. The threshold refers to the decrease of at least 41.2 in the WOMAC physical function score and it is derived based on 1-category improvement on PGI-S scale. In reported data, 'Yes' infers percentage of participants who have achieved threshold whereas 'No' infers percentage of participants who have not achieved threshold. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. Outcome measure was evaluated based on data from in-trial period and it was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)
Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in SF-36 Physical Functioning Score (Yes/No)	Percentage of participants who achieved threshold for clinically meaningful within-participant change in SF-36 physical function score is presented. Threshold refers to increase of at least 11.4 in SF-36 physical functioning score & it is derived based on 1-category improvement on PGI-S scale. 'Yes' infers percentage of participants who achieved threshold; 'No' infers percentage of participants who have not achieved threshold. SF-36: self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, & general health perception. Each SF-36 domain and component summary score ranges from 0-100, higher scores mean better participant health status. Outcome measure was evaluated based on data from in-trial period: uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)
Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 30% (Yes/No)	Percentage of participants who achieved ≥30% pain intensity reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥30% pain intensity reduction whereas 'No' infers percentage of participants who have not achieved ≥30% pain intensity reduction. Response at visit was derived from the pain diary data as an average score over 4 days interval leading up to visit-related washout period for pain medication. Pain intensity was assessed on an 11-point NRS over the past 24 hours (before each specified visit), where a score of 0 indicated "no pain" and a score of 10 indicated "worst possible pain", where higher the score, greater the pain intensity. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)
Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 50% (Yes/No)	Percentage of participants who achieved ≥50% pain intensity reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥50% pain intensity reduction whereas 'No' infers percentage of participants who have not achieved ≥50% pain intensity reduction. Response at visit was derived from the pain diary data as an average score over 4 days interval leading up to visit-related washout period for pain medication. Pain intensity was assessed on an 11-point NRS over the past 24 hours (before each specified visit), where a score of 0 indicated "no pain" and a score of 10 indicated "worst possible pain", where higher the score, greater the pain intensity. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.	From baseline (week 0) to end of treatment (week 68)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Publications and helpful links

General Publications

• Bliddal H, Bays H, Czernichow S, Udden Hemmingsson J, Hjelmesaeth J, Hoffmann Morville T, Koroleva A, Skov Neergaard J, Velez Sanchez P, Wharton S, Wizert A, Kristensen LE; STEP 9 Study Group. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. N Engl J Med. 2024 Oct 31;391(17):1573-1583. doi: 10.1056/NEJMoa2403664.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Actual): July 24, 2023
• Study Completion (Actual): September 8, 2023

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Estimated): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 10, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide
• Other Study ID Numbers: NN9536-4578; U1111-1246-5824 (Other Identifier: WHO); 2020-000204-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No