AMAZE 2: A Research Study Investigating How Well the Medicine NNC0487-0111 Helps People With Excess Body Weight and Type 2 Diabetes Lose Weight (AMAZE 2)

Efficacy and Safety of NNC0487-0111 s.c. Once-weekly in Participants With Overweight or Obesity, and Type 2 Diabetes (AMAZE 2)

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 type 2 diabetes. 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 (treatment that has no active medicine in it). Which treatment participants get is decided by chance.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Diabetes Mellitus; Overweight
• Intervention / Treatment: Drug: NNC0487-0111; Drug: Placebo (matched to NNC0487-0111)

• Study Type: Interventional
• Enrollment (Estimated): 630
• Phase: Phase 3

Contacts and Locations

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

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1119ACU
    • Recruiting
    • Kynet Recoleta
  • Córdoba, Argentina, X5008
    • Recruiting
    • Centro Medico Privado CEMAIC
  • Santa Fe, Argentina, S3000FSO
    • Recruiting
    • CEDIR - Centro de diagnóstico y rehabilitación Santa Fe
  • Buenos Aires
    • Manuel Alberti, Buenos Aires, Argentina, B1669
      • Not yet recruiting
      • MICA- Medicina e Investigación Cardiometabólica
• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 80030-480
      • Recruiting
      • Cline Research Center
  • São Paulo
    • Campinas, São Paulo, Brazil, 13060-803
      • Recruiting
      • PUCCAMP - Hospital e Maternidade Celso Pierro
    • São Paulo, São Paulo, Brazil, 05403-000
      • Not yet recruiting
      • Centro de Pesquisa Clínica do Hospital das Clínicas da Faculdade de Medicina da USP
    • São Paulo, São Paulo, Brazil, 01228-200
      • Recruiting
      • CPCLIN - Centro de Pesquisas Clínicas
• Croatia
  • Karlovac, Croatia, 47000
    • Recruiting
    • Opća bolnica Karlovac
  • Krapinske Toplice, Croatia, 49217
    • Recruiting
    • Specijalna Bolnica za medicinsku rehabilitaciju Krapinske Toplice_Endocrinology
  • Opatija, Croatia, 51 410
    • Recruiting
    • Specijalna bolnica Thalassotherapia
  • Osijek, Croatia, 31000
    • Recruiting
    • Poliklinika SLAVONIJA OSIJEK
  • Pula, Croatia, 52100
    • Recruiting
    • Opca bolnica Pula
  • Solin, Croatia, 21210
    • Recruiting
    • Poliklinika za oftalmologiju optometriju i neurologiju Lux
  • Varaždin, Croatia, 42 000
    • Recruiting
    • Opca bolnica Varazdin_Endocrinology
  • Zagreb, Croatia, 10000
    • Recruiting
    • Poliklinika Solmed
• Hungary
  • Balatonfüred, Hungary, 8230
    • Not yet recruiting
    • DRC Kft.
  • Budapest, Hungary, 1032
    • Not yet recruiting
    • Szent Margit Rendelőintézet Nonprofit Kft.
  • Budapest, Hungary, 1102
    • Not yet recruiting
    • PVN Kutató Kft.
  • Budapest, Hungary, 1083
    • Completed
    • Semmelweis Egyetem
  • Budapest, Hungary, 1134
    • Not yet recruiting
    • Észak-Pesti Centrumkórház Honvédkórház - Diabetológia Szakrendelés
  • Budapest, Hungary, H-1213
    • Not yet recruiting
    • Trantor 99 Bt
  • Kaposvár, Hungary, 7400
    • Not yet recruiting
    • Somogy Varmegyei Kaposi Mor Oktato Korhaz
  • Csongrád-Csanád
    • Szeged, Csongrád-Csanád, Hungary, 6725
      • Not yet recruiting
      • Szegedi Tudomanyegyetem St Györgyi Albert Klinikai Központ
• Italy
  • Milan, Italy, 20132
    • Not yet recruiting
    • IRCCS Ospedale San Raffaele Milano
  • Palermo, Italy, 90127
    • Not yet recruiting
    • Dip. di Medicina Interna Policlinico Universitario Palermo
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Not yet recruiting
      • Dip. Med. Chir. delle malattie digestive, epatiche ed endo-meta - UOC Endocrinologia e prevenzione e cura del diabete
  • Lazio
    • Rome, Lazio, Italy, 00161
      • Not yet recruiting
      • Universita Degli Studi Di Roma La Sapienza - Policlinico Umberto I Medicina Sperimentale
  • Lombardy
    • Milan, Lombardy, Italy, 20159
      • Not yet recruiting
      • Grande Ospedale Metropolitano Niguarda - Dipartimento Medico Polispecialistico - Diabetologia
  • Sicily
    • Palermo, Sicily, Italy, 90127
      • Not yet recruiting
      • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone - PSD Nutrizione Clinica, Obesità e Metabolismo
• Mexico
  • Puebla City, Mexico, 72190
    • Not yet recruiting
    • Consultorio de Endocrinología y Pediatría
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44670
      • Not yet recruiting
      • Centro de Investigacion Clinica Endocrinologica de Jalisco
  • Mexico City
    • Col Roma Norte, Mexico City, Mexico, 06700
      • Not yet recruiting
      • Clinstile S.A. de C.V.
  • México, D.F.
    • Distrito Federal, México, D.F., Mexico, 14080
      • Not yet recruiting
      • Instituto Nacional de Nutricion - Unidad de Inv de Enf Metab
  • Nuevo León
    • San Nicolás de los Garza, Nuevo León, Mexico, 66465
      • Not yet recruiting
      • Unidad Medica para la Salud Integral (UMSI)
  • Oaxaca
    • Oaxaca City, Oaxaca, Mexico, 68020
      • Not yet recruiting
      • Centro de Investigacion Clinica de Oaxaca (CICLO)
• Romania
  • Bacau, Romania, 600154
    • Recruiting
    • CMI Dr. Pletea Noemi SRL
  • Bucharest, Romania, 013764
    • Recruiting
    • SC Nutrilife SRL
  • Bucharest, Romania, 050913
    • Recruiting
    • Diabet Med SRL
  • Bucharest, Romania, 020359
    • Recruiting
    • SC Clinica Diabnutrimed S.R.L.
  • Constanța, Romania, 900512
    • Recruiting
    • Cmi Dr. Cojocaru Cristina
  • Craiova, Romania, 200692
    • Not yet recruiting
    • A&C Medical Prime S.R.L.
  • Satu Mare, Romania, 440055
    • Recruiting
    • Spital Judetean De Urgenta Satu Mare
  • Dolj
    • Craiova, Dolj, Romania, 200515
      • Recruiting
      • S.C. Top Diabet Srl
  • Mureș County
    • Reghin, Mureș County, Romania, 545300
      • Recruiting
      • Poli Cardinal Med Srl
• Slovakia
  • Levice, Slovakia, 93401
    • Recruiting
    • DIA - KONTROL s.r.o.
  • Rimavská Sobota, Slovakia, 979 01
    • Recruiting
    • OLIVER - MED s.r.o.
  • Trebišov, Slovakia, 075 01
    • Recruiting
    • Areteus s.r.o.
  • Trebišov, Slovakia, 075 01
    • Not yet recruiting
    • Areteus s.r.o.
  • Ľubochňa, Slovakia, 03491
    • Recruiting
    • Narodny Endokrinologicky a diabetologicky ustav
  • Šahy, Slovakia, 93601
    • Recruiting
    • Peter Farkas MD, s.r.o.
  • Šurany, Slovakia, 942 01
    • Recruiting
    • DEImedi, s. r. o.
• South Korea
  • Gwangju, South Korea, 61469
    • Recruiting
    • Chonnam National University Hospital_Endocrinology
  • Seoul, South Korea, 02447
    • Recruiting
    • Kyunghee University Medical Center_Endocrinology
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital_Endocrinology
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System_Endocrinology
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center_Endocrinology
  • Seoul, South Korea, 07345
    • Recruiting
    • The Catholic University of Korea, Yeouido ST. Mary's Hospital_Endocrinology
  • Gyeonggi-do
    • Seoungnam-si, Gyeonggi-do, South Korea, 13620
      • Recruiting
      • Seoul National University Bundang Hospital_Endocrinology
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • Univ of Alabama Birmingham
  • California
    • Escondido, California, United States, 92025
      • Recruiting
      • Headlands Research California, LLC
    • Lomita, California, United States, 90717
      • Recruiting
      • Torrance Clinical Research Institute, Inc.
    • Walnut Creek, California, United States, 94598
      • Recruiting
      • Diablo Clinical Research, Inc.
  • Florida
    • Fleming Island, Florida, United States, 32003
      • Recruiting
      • Northeast Research Institute
    • Jacksonville, Florida, United States, 32216
      • Recruiting
      • Jacksonville Ctr Clin Res
    • Orlando, Florida, United States, 32825
      • Recruiting
      • Florida Institute for Clinical Research, LLC
    • Oviedo, Florida, United States, 32765
      • Recruiting
      • Oviedo Medical Research, LLC
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Recruiting
      • International Diabetes Center
  • New York
    • West Seneca, New York, United States, 14224
      • Recruiting
      • Southgate Medical Group, LLP
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Recruiting
      • Spartanburg Medical Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Recruiting
      • M3 Wake Research Chattanooga
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center - Lingvay
    • Houston, Texas, United States, 77079
      • Recruiting
      • PlanIt Research, PLLC
  • Virginia
    • Richmond, Virginia, United States, 23294
      • Recruiting
      • National Clin Res Inc.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female (sex at birth).
• Age 18 years or above at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus more than equal to (≥) 180 days before screening.
• Treatment with lifestyle intervention, and/or 0-3 marketed oral antidiabetic drugs (OAD)s (metformin, α-glucosidase inhibitors (AGI), glinides, sodium-glucose cotransporter 2 inhibitor (SGLT2i), thiazolidinediones, or sulfonylureas (SU) as a single agent or in combination) according to local label. Treatment with oral antidiabetic drugs should be stable (same drug(s), dose and dosing frequency) before screening.
• Haemoglobin A1c (HbA1c) 7-10% [53-86 (millimoles per mole) mmol/mol] (both inclusive) as measured by the central laboratory at screening.

Exclusion Criteria:

• Renal impairment with estimated Glomerular Filtration Rate (eGFR) less than (<) 30 milliliter per minute per meter square (mL/min/1.73 m^2) [2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula], at screening.
• Participant with diabetic retinopathy or maculopathy who received treatment with retinal photocoagulation, vitrectomy or anti-Vascular Endothelial Growth Factor (anti-VEGF) before screening or are expected to require treatment after screening. Diabetic retinopathy or maculopathy must be verified by an eye examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
• Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire question 8.
• Recurrent severe hypoglycaemic episodes within the last year as judged by the investigator.
• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

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 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 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 3; Participants will be randomized to receive NNC0487-0111 dose level 3 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.
Experimental: NNC0487-0111 dose level 4; Participants will be randomized to receive NNC0487-0111 dose level 4 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 (%) of body weight.	From baseline (week 0) to (week 84)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in waist circumference	Measured as centimetre (cm).	From baseline (week 0) to (week 84)
Change in glycated haemoglobin (HbA1c)	Measured as percentage (%) of HbA1c.	From baseline (week 0) to (week 84)
Change in systolic blood pressure (SBP)	Measured as millimetre of mercury (mmHg).	From baseline (week 0) to (week 84)
Change in Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) physical function score	Measured as score on a scale. IWQOL-Lite-CT measures weight-related physical functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. The physical function score ranges from 0-100. Higher scores indicate better levels of functioning.	From baseline (week 0) to (week 84)
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. The physical functioning ranges from 19.0 to 57.6. Higher scores indicate better functional health and well-being.	From baseline (week 0) to (week 84)
Change in body weight	Measured as kilogram (kg).	From baseline (week 0) to (week 84)
Change in body mass index (BMI)	Measured as kilograms per meter squared (kg/m^2).	From baseline (week 0) to (week 84)
Change in IWQOL-Lite-CT: Physical, Psychosocial, Total score	Measured as score on a scale. IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. The physical function score ranges from 0-100. Higher scores indicate better levels of functioning.	From baseline (week 0) to (week 84)
Achievement of HbA1c < 7.0% (Yes/No)	Measured as number of participants	From baseline (week 0) to (week 84)
Achievement of HbA1c ≤ 6.5% (Yes/No)	Measured as number of participants	From baseline (week 0) to (week 84)
Achievement of HbA1c < 5.7% (Yes/No)	Measured as number of participants	From baseline (week 0) to (week 84)
Change in fasting plasma glucose (FPG) (mmol/L)	Measured as millimoles per liter (mmol/L)	From baseline (week 0) to (week 84)
Change in fasting plasma glucose (FPG) (mg/dL)	Measured as milligram per deciliter (mg/dL)	From baseline (week 0) to (week 84)
Change in fasting insulin	Measured as ratio to baseline.	From baseline (week 0) to (week 84)
Change in urinary albumin-to-creatinine ratio (UACR)	Measured as ratio to baseline.	From baseline (week 0) to (week 84)
Change in diastolic blood pressure	Measured as mmHg.	From baseline (week 0) to (week 84)
Change in high-sensitivity C-reactive protein (hsCRP)	Measured as ratio to baseline.	From baseline (week 0) to (week 84)
Number of Treatment Emergent Adverse Events (TEAEs)	Measured as count of events.	From baseline (week 0) to week 88
Number of Treatment Emergent Serious Adverse Events (TESAEs)	Measured as count of events.	From baseline (week 0) to week 88
Number of Treatment Emergent Adverse Events (TEAEs) leading to permanent treatment discontinuation	Measured as count of events.	From baseline (week 0) to week 88
Number of treatment emergent clinically significant hypoglycaemic episodes (level 2) (< 3.0 mmol/L (54 mg/dL), confirmed by a blood glucose (BG) meter)	Measured as number of episodes	From baseline (week 0) to week 88
Number of treatment emergent severe hypoglycaemic episodes (level 3): hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold	Measured as number of episodes	From baseline (week 0) to week 88
Change in Total cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 84)
Change in High-density lipoprotein (HDL) cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 84)
Change in Low-density lipoprotein (LDL) cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 84)
Change in Very low-density lipoprotein (VLDL) cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 84)
Change in Non-HDL cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 84)
Change in Triglycerides	Measured as ratio to baseline.	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 7, 2028
• Study Completion (Estimated): August 7, 2028

Study Registration Dates

• First Submitted: April 9, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 16, 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: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Diabetes Mellitus
• Other Study ID Numbers: NN9490-8024; U1111-1313-6325 (Other Identifier: World Health Organization (WHO)); 2024-520441-23 (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