A Research Study Investigating How Well the Medicine NNC0487-0111 Helps People With Excess Body Weight and Knee Osteoarthritis Lose Weight and Reduce Pain (AMAZE 5)

Efficacy and Safety of NNC0487-0111 s.c. Once-weekly in Participants With Overweight or Obesity, and Knee Osteoarthritis (AMAZE 5)

The purpose of this clinical study is to find out if NNC0487-0111 is safe and effective for treating people who have excess body weight and knee osteoarthritis. There are 2 study treatments in this study taken as injections under the skin once a week. Participants will either get NNC0487-0111 (the treatment being tested) or Placebo (a treatment that has no active medicine in it). Which treatment participants get is decided by chance.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Knee Osteoarthritis (OA)
• Intervention / Treatment: Drug: NNC0487-0111; Drug: Placebo (matched to NNC0487-0111 )

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Australia
  • New South Wales
    • Botany, New South Wales, Australia, 2019
      • Recruiting
      • Emeritus Research Sydney
    • Darlinghurst, New South Wales, Australia, 2010
      • Recruiting
      • Momentum Clinical Research Darlinghurst
    • St Leonards, New South Wales, Australia, 2065
      • Recruiting
      • Kolling Institute
  • Queensland
    • Chelmer, Queensland, Australia, 4068
      • Recruiting
      • Heart of Australia
    • Maroochydore, Queensland, Australia, 4558
      • Recruiting
      • Coastal Digestive Health
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • Recruiting
    • UMHAT Sveti Georgi EAD, Plovdiv
  • Sofia, Bulgaria, 1407
    • Recruiting
    • MC Excelsior OOD
  • Sofia, Bulgaria, 1231
    • Recruiting
    • MC Dr. Atanasov EOOD
  • Sofia, Bulgaria, 1527
    • Recruiting
    • UMHAT Tsaritsa Yoanna - ISUL EAD, Orthopaedics and Traumatology
  • Sofia, Bulgaria, 1606
    • Recruiting
    • MMA MHAT - Sofia, Rheumatology clinic
  • Sofia, Bulgaria, 1612
    • Recruiting
    • UMHAT Sveti Ivan Rilski EAD, Rheumatology
• Canada
  • Québec, Canada, G2J OC4
    • Recruiting
    • Alpha Recherche Clinique - Lebourgneuf
  • Alberta
    • Calgary, Alberta, Canada, T2W 4X9
      • Not yet recruiting
      • Laser Rejuvenation Clinics Inc.
  • Ontario
    • Guelph, Ontario, Canada, N1H 1B1
      • Recruiting
      • Dawson Clinical Research
    • Hamilton, Ontario, Canada, L8L 5G4
      • Not yet recruiting
      • Hamilton Medical Rsrch Grp
  • Quebec
    • Trois-Rivières, Quebec, Canada, G8Z 1Y2
      • Recruiting
      • Centre de Recherche Musculo
• Denmark
  • Aarhus N, Denmark, 8200
    • Recruiting
    • Aarhus Universitetshospital - Klinik for Led og bindevævssygdomme
  • Frederiksberg, Denmark, 2000
    • Recruiting
    • Frederiksberg Hospital - Parker Institutet (Artrose)
  • Herlev, Denmark, 2730
    • Recruiting
    • Sanos Clinic - Herlev
• Greece
  • Athens, Greece, 115 27
    • Recruiting
    • Laiko General Hospital Of Athens - 1st department of Internal Medicine
  • Athens, Greece, 11525
    • Recruiting
    • Athens Medical Center S.A. (Iatriko Psychicou) - Department of Internal Medicine & Metabolic Diseases
  • Athens, Greece, 11528
    • Recruiting
    • General Hospital Of Athens Alexandra - Clinical Therapeutics
  • Marousi, Greece, 15125
    • Recruiting
    • Athens Medical Center S.A. (Iatriko Athinon) - Diabetes and Obesity Unit
  • Thessaloniki, Greece, 54635
    • Recruiting
    • NextHealth S.A. - Department of Endocrinology, Metabolism & Diabetes
  • Thessaloniki, Greece, 57001
    • Recruiting
    • Thermi Clinic S.A. - Diabetes and Internal Medicine Department
  • Attica
    • Chaïdári, Attica, Greece, 12461
      • Not yet recruiting
      • University General Hospital Attikon General Hospital Of West Attica H Agia Varvara - 2nd dept of Internal medicine
• Italy
  • Campania
    • Naples, Campania, Italy, 80131
      • Not yet recruiting
      • AOU Federico II Di Napoli - DAI Endocr. Diab. Andro. e Nutr. - UOC Medicina Interna e Nutrizione Clinica
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41126
      • Not yet recruiting
      • Ospedale Civile di Baggiovara - UOC Endocrinologia
  • Friuli Venezia Giulia
    • Udine, Friuli Venezia Giulia, Italy, 33100
      • Not yet recruiting
      • Ospedale S. Maria della Misericordia - Reparto Endocrinologia e Malattie del Metabolismo
  • Lazio
    • Rome, Lazio, Italy, 00128
      • Not yet recruiting
      • Pol. Uni. Campus Biomedico - UOC Endocrinologia e Diabetologia
  • Lombardy
    • Milan, Lombardy, Italy, 20149
      • Not yet recruiting
      • Auxologico San Luca - Endocrinologia e Malattie del Metabolismo
    • San Donato Milanese, Lombardy, Italy, 20097
      • Not yet recruiting
      • Policlinico San Donato di Milano S.p.A - UOS Endocrinologia e del Servizio di Nutrizione Clinica e Prevenzione Cardiometabolica
  • Veneto
    • Verona, Veneto, Italy, 37126
      • Not yet recruiting
      • Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Civile Maggiore Borgo Trento - U.O. Reumatologia
• Poland
  • Bialystok, Poland, 15-879
    • Not yet recruiting
    • ClinicMed Daniluk, Nowak Spółka Komandytowa
  • Bialystok, Poland, 15-879
    • Recruiting
    • ClinicMed Daniluk, Nowak Spółka Komandytowa
  • Bydgoszcz, Poland, 85-605
    • Recruiting
    • Centrum Medyczne Intercor Sp. z o.o.
  • Bydgoszcz, Poland, 85-605
    • Not yet recruiting
    • Centrum Medyczne Intercor Sp. z o.o.
  • Krakow, Poland, 31-530
    • Recruiting
    • Centermed Kraków Sp. Z o.o.
  • Krakow, Poland, 31-826
    • Recruiting
    • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o.
  • Krakow, Poland, 31-530
    • Not yet recruiting
    • Centermed Kraków Sp. Z o.o.
  • Krakow, Poland, 31-826
    • Not yet recruiting
    • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o.
  • Warsaw, Poland, 02-637
    • Recruiting
    • Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. prof. dr hab. med. Eleonory Reicher
  • Warsaw, Poland, 02-637
    • Not yet recruiting
    • Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. prof. dr hab. med. Eleonory Reicher
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-351
      • Not yet recruiting
      • "Zdrowie Osteo-Medic" s.c. Lidia i Artur Racewicz, Agnieszka i Jerzy Supronik
    • Bialystok, Podlaskie Voivodeship, Poland, 15-351
      • Recruiting
      • "Zdrowie Osteo-Medic" s.c. Lidia i Artur Racewicz, Agnieszka i Jerzy Supronik
• Spain
  • A Coruña, Spain, 15006
    • Recruiting
    • Instituto Medico Quirurgico San Rafael
  • Badalona, Spain, 08916
    • Not yet recruiting
    • Hospital Germans Trias I Pujol
  • Ferrol, Spain, 15405
    • Recruiting
    • Hospital Naval Ferrol
  • Madrid, Spain, 28038
    • Not yet recruiting
    • Centro Especialidades Hermanos Sangro
  • Málaga, Spain, 29004
    • Recruiting
    • Hospital QuironSalud Malaga
  • San Sebastián de Los Reyes (Madrid), Spain, 28702
    • Recruiting
    • Hospital Infanta Sofía
  • Santander, Spain, 39008
    • Recruiting
    • Hospital Universitario Marqués de Valdecilla
  • Santiago de Compostela, Spain, 15705
    • Recruiting
    • Hospital HM La Esperanza
  • Seville, Spain, 41003
    • Recruiting
    • Clínica Nuevas Tecnologías en Diabetes y Endocrinología
  • Seville, Spain, 41010
    • Recruiting
    • H. Infanta Luisa_Endocrino y Obesidad
  • Valencia, Spain, 46014
    • Recruiting
    • Hospital General de Valencia
• Turkey (Türkiye)
  • Altındağ/Ankara, Turkey (Türkiye), 06230
    • Recruiting
    • Ankara Üniversitesi Sağlık Uygulama ve Araştırma Hastaneleri- Fiziksel Tıp ve Rehabilitasyon
  • Bahçelievler/İstanbul, Turkey (Türkiye), 34186
    • Recruiting
    • İstanbul Fizik Tedavi ve Rehabilitasyon Eğitim ve Araştırma Hastanesi
  • Kepez/Çanakkale Merkez/Çanakkale, Turkey (Türkiye), 17110
    • Not yet recruiting
    • Çanakkale Onsekiz Mart Üniversitesi Sağlık Araştırma ve Uygulama Hastanesi-Fiziksel Tıp ve Rehabilitasyon
  • Merkez/Battalgazi/Malatya, Turkey (Türkiye), 44280
    • Not yet recruiting
    • İnönü Üniversitesi Turgut Özal Tıp Merkezi Hastanesi-Fiziksel Tıp ve Rehabilitasyon
  • Trabzon Merkez/Ortahisar/Trabzon, Turkey (Türkiye), 61080
    • Recruiting
    • Karadeniz Teknik Üniversitesi Farabi Hastanesi- Fiziksel Tıp ve Rehabilitasyon
  • Yuregir/Adana, Turkey (Türkiye), 01060
    • Recruiting
    • Adana Şehir Eğitim ve Araştırma Hastanesi-Fizik Tedavi ve Rehabilitasyon
  • Çankaya/Ankara, Turkey (Türkiye), 06800
    • Recruiting
    • Ankara Bilkent Şehir Hastanesi- Fizik Tedavi ve Rehabilitasyon
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Recruiting
      • Arizona Research Center, Inc.
  • California
    • Walnut Creek, California, United States, 94598
      • Recruiting
      • Diablo Clinical Research, Inc.
  • Connecticut
    • Hamden, Connecticut, United States, 06517
      • Recruiting
      • Chase Medical Research LLC
    • Waterbury, Connecticut, United States, 06708
      • Recruiting
      • Chase Medical Research LLC
  • Florida
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • Zenith Clinical Research
    • Jacksonville, Florida, United States, 32256
      • Recruiting
      • CNS Healthcare
    • Miami Lakes, Florida, United States, 33016
      • Recruiting
      • Angels Clinical Research Institute
  • Georgia
    • Conyers, Georgia, United States, 30094
      • Recruiting
      • Hope Clin Res & Wellness
    • Decatur, Georgia, United States, 30030
      • Recruiting
      • CenExel iResearch, LLC
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Recruiting
      • Elite Clinical Trials
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • Recruiting
      • MedVadis Research Watertown
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Recruiting
      • Jubilee Clinical Research, Inc.
  • New York
    • Westfield, New York, United States, 14787
      • Recruiting
      • Great Lakes Medical Research
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Recruiting
      • Accellacare and KDCILM, LLC
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Recruiting
      • Coastal Carolina Res Ctr
  • Texas
    • San Antonio, Texas, United States, 78230
      • Recruiting
      • VIP Trials_San Antonio
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Recruiting
      • Charlottesville Med Research
    • Newport News, Virginia, United States, 23606
      • Recruiting
      • Health Res of Hampton Roads
  • Washington
    • Bellevue, Washington, United States, 98007
      • Recruiting
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key inclusion Criteria:

• Male or female (sex at birth).
• Age 18 years or above at the time of signing the informed consent.
• Clinical diagnosis of knee osteoarthritis (American College of Rheumatology criteria) with radiographic changes (Kellgren Lawrence (KL) grades 2 to 3 as per central reading) in target knee. Target knee joint is defined as most symptomatic knee at screening. If pain in knees is equal, the target knee joint will be the dominant leg.
• Symptomatic knee OA with first appearance of pain in the target knee more than (>) 90 days prior to screening and pain in the target knee for > 15 days over the prior 30 days.
• Willingness to complete a 72-hour washout period of analgesics before all visits involving WOMAC Osteoarthritis Index NRS 3.1 (24-hour) (WOMAC) questionnaire (acetaminophen 4 gram (g)/day is allowed as rescue medication up until 24 hours before those visits).

Exclusion Criteria:

• Glycated haemoglobin more than or equal to (≥) 6.5% [(48 millimoles per mole (mmol/mol)] as measured by the central laboratory at screening.
• History of type 1 or type 2 diabetes mellitus as declared by the participant or reported in the medical records.
• Treatment with glucagon-like-peptide-1 (GLP-1) receptor agonists (RA), dual GLP-1/gastric inhibitory peptide (GIP) RAs (or any other GLP-1 based treatment), or amylin analogues before screening.
• Any joint prosthesis or joint replacement in target knee.
• Arthroscopy or injections into target knee within the last 90 days prior to screening.
• Any other joint disease in target knee including gout and pseudogout.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive placebo matched to NNC0487-0111 subcutaneously once weekly as an adjunct to a reduced-calorie diet and increased physical activity.	Drug: Placebo (matched to NNC0487-0111 ); Placebo matched to NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to one of the body parts: thigh, abdomen or upper arm.
Experimental: NNC0487-0111 dose level 1; Participants will be randomized to receive NNC0487-0111 dose level 1 subcutaneously once weekly as an adjunct to a reduced-calorie diet and increased physical activity.	Drug: NNC0487-0111; NNC0487-0111 dose level 1 and dose level 2 will be administered subcutaneously using PDS290 pre-filled pen-injectors to one of the body parts: thigh, abdomen or upper arm.
Experimental: NNC0487-0111 dose level 2; Participants will be randomized to receive NNC0487-0111 dose level 2 subcutaneously once weekly as an adjunct to a reduced-calorie diet and increased physical activity.	Drug: NNC0487-0111; NNC0487-0111 dose level 1 and dose level 2 will be administered subcutaneously using PDS290 pre-filled pen-injectors to one of the body parts: thigh, abdomen or upper arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change in body weight	Measured as percentage (%) of body weight.	From baseline (week 0) to (week 80)
Change in WOMAC Osteoarthritis Index NRS 3.1 (24-hour) (WOMAC) pain score	Measured as score on a scale. Western Ontario and McMaster Universities Arthritis Index (WOMAC) measures symptoms in the areas of pain, stiffness, and physical function. The measure consists of 24 items yielding 3 subscale scores and 1 total score. WOMAC raw scores are transformed to a standardised 0 to 100 score range. Higher scores indicate worse pain, stiffness, physical function, and overall osteoarthritis- related disability.	From baseline (week 0) to (week 80)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in WOMAC physical function score	Measured as score on a scale. Physical function score will be calculated according to the guidelines provided in the WOMAC User Guide XI. Score ranges from 0-100 and higher scores indicate worse physical function.	From baseline (week 0) to (week 80)
Change in SF-36v2® Health Survey Acute (SF-36v2 Acute) physical functioning score	Measured as score on a scale. SF-36v2 Acute measures Health-Related Quality of Life (HRQOL). The measure consists of 36 items yielding 8 health domain scores and 2 component summary scores. SF-36v2 Acute scores are norm-based scores, that is transformed to a scale where the 2009 US general population has a mean of 50 and a standard deviation (SD) of 10. Higher scores indicate better functional health and well-being. The physical functioning ranges from 19.0 to 57.6.	From baseline (week 0) to (week 80)
Change in body weight	Measured as kilogram (kg).	From baseline (week 0) to (week 80)
Change in body mass index (BMI)	Measured as kilograms per meter squared (kg/m^2).	From baseline (week 0) to (week 80)
Change in WOMAC stiffness score	Measured as score on a scale. Stiffness score will be calculated according to the guidelines provided in the WOMAC User Guide XI. Score ranges from 0-100 and higher scores indicate worse stiffness.	From baseline (week 0) to (week 80)
Change in WOMAC total score	Measured as score on a scale. Total score will be calculated according to the guidelines provided in the WOMAC User Guide XI. Total score ranges from 0-100 and higher scores indicate worse overall osteoarthritis- related disability.	From baseline (week 0) to (week 80)
Change in waist circumference	Measured as centimetre (cm).	From baseline (week 0) to (week 80)
Change in systolic blood pressure (SBP)	Measured as millimetre of mercury (mmHg).	From baseline (week 0) to (week 80)
Change in diastolic blood pressure (DBP)	Measured as mmHg.	From baseline (week 0) to (week 80)
Change in total cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in high-density lipoprotein (HDL) cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in low-density lipoprotein (LDL) cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in very low-density lipoprotein (VLDL) cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in non-HDL cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in triglycerides	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in high-sensitivity C-reactive protein (hsCRP)	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in glycated haemoglobin (HbA1c)	Measured as percentage (%) of HbA1c.	From baseline (week 0) to (week 80)
Change in fasting plasma glucose (FPG)	Measured as millimole per liter (mmol/L).	From baseline (week 0) to (week 80)
Number of participants allowed using rescue analgesics during washout period (Yes/no)	Measured as number of participants	From baseline (week 0) to (week 80)
Amount of allowed rescue analgesics used during washout period	Measured as dose of analgesics.	From baseline (week 0) to (week 80)
Use of pain medication (Yes/No)	Measured as number of participants.	From baseline (week 0) to (week 80)
Amount of pain medication used	Measured as dose of pain medication.	From baseline (week 0) to (week 80)
Number of participants with change in pain medication (decrease/no change/increase)	Measured as number of participants.	From baseline (week 0) to (week 80)
Change in knee pain intensity (NRS)	Measured as score on a scale. Knee pain numerical rating scale (NRS) measures knee pain at its worst in the last 24 hours. The measure consists of 1 item. The response scale is an 11-point numeric rating scale from 0 (No knee pain) to 10 (Worst possible knee pain). Higher scores indicate worse pain.	From baseline (week 0) to (week 80)
Number of treatment Emergent Adverse Events (TEAEs)	Measured as number of events.	From baseline (week 0) to week 84
Number of treatment Emergent Serious Adverse Events (TESAEs)	Measured as number of events.	From baseline (week 0) to week 84
Number of TEAEs leading to permanent treatment discontinuation	Measured as number of events.	From baseline (week 0) to week 84

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2026
• Primary Completion (Estimated): August 14, 2028
• Study Completion (Estimated): August 14, 2028

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nutrition Disorders; Arthritis; Joint Diseases; Rheumatic Diseases; Overnutrition; Body Weight; Osteoarthritis; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Osteoarthritis, Knee
• Other Study ID Numbers: NN9490-8026; U1111-1313-6585 (Other Identifier: World Health Organization (WHO)); 2024-520444-42 (Other Identifier: European Medical Agency (EMA))

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