AMAZE 5

RecruitingPhase 3

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

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

Lead sponsor

Novo Nordisk A/S

Asset

Amycretin / zenagamtide

Oral · GLP-1 / amylin

Listed sites

Recruiting sites

Enrollment

400

estimated

Study population

Obesity / overweight, Osteoarthritis

Key I/E criterion

—

Primary endpoints

•Body weight, % change•WOMAC pain

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07481630

Org study IDNN9490-8026

Secondary ID2024-520444-42European Medical Agency (EMA)

Secondary IDU1111-1313-6585World Health Organization (WHO)

Timeline

Milestones

Study first posted2026-03-19actual

Study start2026-04-13actual

Last update posted2026-06-02actual

Primary completion2028-08-14estimated

Study completion2028-08-14estimated

Assets

Investigational agents

Amycretin / zenagamtide

Study populations

Who this study enrolls

Obesity / overweightOsteoarthritis

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

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.

Endpoints (29)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Cardiometabolic biomarkers

Other clinical outcomes

Weight & body composition

Safety / tolerability / PK

Glycemic / diabetes

Patient-reported / QoL

Weight & body composition

4 endpoints

Primary/protocol endpoint

Relative change in body weight

Time frame:From baseline (week 0) to (week 80)

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in body weight

Time frame:From baseline (week 0) to (week 80)

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in body mass index (BMI)

Time frame:From baseline (week 0) to (week 80)

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Change in waist circumference

Time frame:From baseline (week 0) to (week 80)

Waist circumference, change

change from baseline, improvement

Glycemic / diabetes

2 endpoints

Secondary/protocol endpoint

Change in glycated haemoglobin (HbA1c)

Time frame:From baseline (week 0) to (week 80)

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in fasting plasma glucose (FPG)

Time frame:From baseline (week 0) to (week 80)

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Cardiometabolic biomarkers

9 endpoints

Secondary/protocol endpoint

Change in systolic blood pressure (SBP)

Time frame:From baseline (week 0) to (week 80)

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Change in diastolic blood pressure (DBP)

Time frame:From baseline (week 0) to (week 80)

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Secondary/protocol endpoint

Change in total cholesterol

Time frame:From baseline (week 0) to (week 80)

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Secondary/protocol endpoint

Change in high-density lipoprotein (HDL) cholesterol

Time frame:From baseline (week 0) to (week 80)

HDL-C, change

ratio, improvement

LOINC 2085-9

Secondary/protocol endpoint

Change in low-density lipoprotein (LDL) cholesterol

Time frame:From baseline (week 0) to (week 80)

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in very low-density lipoprotein (VLDL) cholesterol

Time frame:From baseline (week 0) to (week 80)

VLDL, change

ratio, improvement

Secondary/protocol endpoint

Change in non-HDL cholesterol

Time frame:From baseline (week 0) to (week 80)

Non-HDL cholesterol, change

ratio, improvement

Secondary/protocol endpoint

Change in triglycerides

Time frame:From baseline (week 0) to (week 80)

Triglycerides, change

ratio, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change in high-sensitivity C-reactive protein (hsCRP)

Time frame:From baseline (week 0) to (week 80)

hs-CRP, change

ratio, improvement

LOINC 30522-7

Patient-reported / QoL

1 endpoint

Secondary/protocol endpoint

Change in SF-36v2® Health Survey Acute (SF-36v2 Acute) physical functioning score

Time frame:From baseline (week 0) to (week 80)

SF-36 physical

change from baseline, improvement

Safety / tolerability / PK

4 endpoints

Secondary/protocol endpoint

Number of participants allowed using rescue analgesics during washout period (Yes/no)

Time frame:From baseline (week 0) to (week 80)

threshold achievement, descriptive

Secondary/protocol endpoint

Number of treatment Emergent Adverse Events (TEAEs)

Time frame:From baseline (week 0) to week 84

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

Number of treatment Emergent Serious Adverse Events (TESAEs)

Time frame:From baseline (week 0) to week 84

Serious AEs (any)

event count, event

Secondary/protocol endpoint

Number of TEAEs leading to permanent treatment discontinuation

Time frame:From baseline (week 0) to week 84

Discontinuation due to AE

event count, event

Other clinical outcomes

9 endpoints

Primary/protocol endpoint

Change in WOMAC Osteoarthritis Index NRS 3.1 (24-hour) (WOMAC) pain score

Time frame:From baseline (week 0) to (week 80)

WOMAC pain

change from baseline, improvement

Secondary/protocol endpoint

Change in WOMAC physical function score

Time frame:From baseline (week 0) to (week 80)

WOMAC function

change from baseline, improvement

Secondary/protocol endpoint

Change in WOMAC stiffness score

Time frame:From baseline (week 0) to (week 80)

change from baseline, improvement

Secondary/protocol endpoint

Change in WOMAC total score

Time frame:From baseline (week 0) to (week 80)

change from baseline, improvement

Secondary/protocol endpoint

Amount of allowed rescue analgesics used during washout period

Time frame:From baseline (week 0) to (week 80)

descriptive

Secondary/protocol endpoint

Use of pain medication (Yes/No)

Time frame:From baseline (week 0) to (week 80)

categorical status, descriptive

Secondary/protocol endpoint

Amount of pain medication used

Time frame:From baseline (week 0) to (week 80)

change from baseline, improvement

Secondary/protocol endpoint

Number of participants with change in pain medication (decrease/no change/increase)

Time frame:From baseline (week 0) to (week 80)

categorical status, descriptive

Secondary/protocol endpoint

Change in knee pain intensity (NRS)

Time frame:From baseline (week 0) to (week 80)

change from baseline, improvement

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.