AMAZE 6: 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 6)

Efficacy and Safety of NNC0487-0111 s.c. Once-weekly in Participants With Overweight or Obesity, and Knee Osteoarthritis (AMAZE 6)

This study is being done to look at the safety and effect of NNC0487-0111 in people with excess body weight and knee osteoarthritis when compared to placebo. 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; Overweight; Osteoarthritis, Knee
• 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
  • British Columbia
    • Surrey, British Columbia, Canada, V3T 2V6
      • Not yet recruiting
      • TLC Diabetes and Endocrinology
  • Ontario
    • Niagara Falls, Ontario, Canada, L2H 1H5
      • Recruiting
      • Your Research Network
  • Quebec
    • Lévis, Quebec, Canada, G6V 0C9
      • Recruiting
      • Alpha Recherche Clinique
    • Montreal, Quebec, Canada, H4N 2W2
      • Recruiting
      • Centre Medical Acadie
    • Québec, Quebec, Canada, G3K 2P8
      • Recruiting
      • Alpha Recherche Clinique
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Recruiting
      • Centre de Recherche du CHUS
• 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, 10676
    • Recruiting
    • Evangelismos S.A. - Endocrinology department
  • 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
      • Recruiting
      • University General Hospital Attikon General Hospital Of West Attica H Agia Varvara - 2nd dept of Internal medicine
• Italy
  • 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
    • Rome, Lazio, Italy, 00128
      • Not yet recruiting
      • Casa della Salute di Ceccano - Ambulatori Campus Biomedico
  • Lombardy
    • Milan, Lombardy, Italy, 20149
      • Not yet recruiting
      • Auxologico San Luca - Endocrinologia e Malattie del Metabolismo
    • Milan, Lombardy, Italy, 20157
      • Not yet recruiting
      • Ospedale Galeazzi S.p.A. - INCO - Istituto Nazionale per la Cura dell'Obesità
    • 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
    • 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
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-351
      • Recruiting
      • "Zdrowie Osteo-Medic" s.c. Lidia i Artur Racewicz, Agnieszka i Jerzy Supronik
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Recruiting
    • Latin Clinical Trial Center Puerto Rico
• Spain
  • A Coruña, Spain, 15006
    • Not yet 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 Marques 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)
  • Bahçelievler/İstanbul, Turkey (Türkiye), 34186
    • Recruiting
    • İstanbul Fizik Tedavi ve Rehabilitasyon Eğitim ve Araştırma Hastanesi
  • Edirne, Turkey (Türkiye), 22030
    • Recruiting
    • Trakya Üniversitesi Tıp Fakültesi Hastanesi-Fizik Tedavi ve Rehabilitasyon
  • Fatih/İstanbul, Turkey (Türkiye), 34116
    • Recruiting
    • Istanbul Üniversitesi- Istanbul Tıp Fakültesi Esnaf Hastanesi Poliklinikleri Fiziksel Tıp Ve Rehabilitasyon Anabilim Dalı
  • Yuregir/Adana, Turkey (Türkiye), 01060
    • Recruiting
    • Adana Şehir Eğitim ve Araştırma Hastanesi-Fizik Tedavi ve Rehabilitasyon
  • Yıldırım/Bursa, Turkey (Türkiye), 16310
    • Recruiting
    • Bursa Yüksek İhtisas Eğitim ve Araştırma Hastanesi-Fizik Tedavi ve Rehabilitasyon
  • Çankaya/Ankara, Turkey (Türkiye), 06800
    • Recruiting
    • Ankara Bilkent Şehir Hastanesi- Fizik Tedavi ve Rehabilitasyon
  • Çankaya/Ankara, Turkey (Türkiye), 06800
    • Recruiting
    • SBÜ Ankara Gaziler Fizik Tedavi Ve Rehabilitasyon Eğitim Ve Araştırma Hastanesi
• United States
  • California
    • Escondido, California, United States, 92025
      • Recruiting
      • Neighborhood Healthcare
    • Lancaster, California, United States, 93534
      • Recruiting
      • First Valley Medical Group
    • Palm Springs, California, United States, 92262
      • Recruiting
      • Desert Oasis Healthcare
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Recruiting
      • Chase Medical Research LLC
  • Florida
    • Jacksonville, Florida, United States, 32205
      • Recruiting
      • Westside Center For Clinical Research
    • Jacksonville, Florida, United States, 32256
      • Recruiting
      • CNS Healthcare
    • Naples, Florida, United States, 34102
      • Recruiting
      • Advanced Res for Health Improve
  • Illinois
    • Gurnee, Illinois, United States, 60031
      • Recruiting
      • Clinical Investigation Spec Gurnee
    • Skokie, Illinois, United States, 60077
      • Recruiting
      • Evanston Premier Hlthcr Res
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Recruiting
      • Monroe Biomedical Research, LLC
  • Michigan
    • Troy, Michigan, United States, 48098-6368
      • Recruiting
      • Arcturus Healthcare, PLC.
  • Missouri
    • Springfield, Missouri, United States, 65807
      • Recruiting
      • Clinvest Research
  • New York
    • New York, New York, United States, 10021
      • Not yet recruiting
      • Hospital for Special Surgery
    • New York, New York, United States, 10016
      • Not yet recruiting
      • NYU Langone Orthopedic Center
  • North Carolina
    • Statesville, North Carolina, United States, 28625
      • Recruiting
      • Piedmont Healthcare/Research
  • Oregon
    • Portland, Oregon, United States, 97202
      • Recruiting
      • Northwest Research Center
  • Texas
    • Dallas, Texas, United States, 75208
      • Not yet recruiting
      • Mercy Family Clinic
  • Virginia
    • 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 (OA) (American College of Rheumatology criteria) with radiographic changes (Kellgren Lawrence [KL] grades 2 to 4 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 > 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 grams (g)/day is allowed as rescue medication up until 24 hours before those visits)

Key Exclusion Criteria:

• Glycated haemoglobin (HbA1c) ≥ 6.5% (48 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

2

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; Participants will be randomized to receive 1 of the 2 dose levels of NNC0487-0111 subcutaneously once weekly as an adjunct to a reduced-calorie diet and increased physical activity.	Drug: NNC0487-0111; NNC0487-0111 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 change in body weight.	From baseline (week 0) to week 80
Change in Western Ontario and McMaster Universities Osteoarthritis Index Numerical Rating Scale (NRS) 3.1 (24-hour) (WOMAC) pain score	WOMAC is a participant reported outcome (PRO) measures symptoms in the areas of pain, stiffness, and physical function in participants with osteoarthritis of the hip and/or knee. 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. Subscale score for pain ranges 0-100, where higher score indicates worse pain. Measured as score on a scale.	From baseline (week 0) to week 80

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in WOMAC physical function score	WOMAC is a PRO measures symptoms in the areas of pain, stiffness, and physical function in participants with osteoarthritis of the hip and/or knee. 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. Subscale score for physical function ranges 0-100, where higher score indicates worse physical function. Measured as score on a scale.	From baseline (week 0) to week 80
Change in SF-36v2® Health Survey Acute (SF-36v2 Acute) physical functioning score	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, i.e. 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. Measured as score on a scale.	From baseline (week 0) to week 80
Change in body weight	Measured as kilograms (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	WOMAC is a PRO measures symptoms in the areas of pain, stiffness, and physical function in participants with osteoarthritis of the hip and/or knee. 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. Subscale score for stiffness ranges 0-100, where higher score indicates worse stiffness. Measured as score on a scale.	From baseline (week 0) to week 80
Change in WOMAC total score	WOMAC is a PRO measures symptoms in the areas of pain, stiffness, and physical function in participants with osteoarthritis of the hip and/or knee. 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. Total score ranges 0-100, where higher score indicates worse pain, stiffness, physical function and overall osteoarthritis related disability. Measured as score on a scale.	From baseline (week 0) to week 80
Change in waist circumference	Measured as centimetres (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
Ratio to baseline: change in total cholesterol	Measured as ratio.	From baseline (week 0) to week 80
Ratio to baseline: change in high-density lipoprotein (HDL) cholesterol	Measured as ratio.	From baseline (week 0) to week 80
Ratio to baseline: change in low-density lipoprotein (LDL) cholesterol	Measured as ratio.	From baseline (week 0) to week 80
Ratio to baseline: change in very low-density lipoprotein (VLDL) cholesterol	Measured as ratio.	From baseline (week 0) to week 80
Ratio to baseline: change in non-HDL cholesterol	Measured as ratio.	From baseline (week 0) to week 80
Ratio to baseline: change in triglycerides	Measured as ratio.	From baseline (week 0) to week 80
Ratio to baseline: change in high-sensitivity C-reactive protein (hsCRP)	Measured as ratio.	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 litre (mmol/L).	From baseline (week 0) to week 80
Number of participants with use of allowed rescue analgesics during washout period (yes/no)	Measured as count 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
Number of participants with use of pain medication (yes/no)	Measured as count 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 count of participants.	From baseline (week 0) to week 80
Change in knee pain intensity score (NRS)	NRS item is PRO measures knee pain at its worst. 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. Measured as score on a scale.	From baseline (week 0) to week 80
Number of treatment emergent adverse events (TEAEs)	Measured as events.	From baseline (week 0) to week 84
Number of treatment emergent serious adverse events (TESAEs)	Measured as events.	From baseline (week 0) to week 84
Number of TEAEs leading to permanent treatment discontinuation	Measured as 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 20, 2026
• Primary Completion (Estimated): August 14, 2028
• Study Completion (Estimated): August 14, 2028

Study Registration Dates

• First Submitted: March 29, 2026
• First Submitted That Met QC Criteria: March 29, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 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; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Osteoarthritis, Knee
• Other Study ID Numbers: NN9490-8294; U1111-1313-6954 (Other Identifier: World Health Organization (WHO)); 2024-520445-23 (Other Identifier: European Medicines Agency)

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