ZENAGAMTIDE for Overweight or obesity | Knee osteoarthritis

Inclusion criteria

• {"criterion_text":"- 1. Male or female (sex at birth).\n- 2. Age 18 years or above at the time of signing the informed consent.\n- 3. Body mass index (BMI) CCI kg/m2 at screening.\n- 4. CCI\n- 5. 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 kneea. 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.\n- 6. 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.\n- 7. 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 g/day is allowed as rescue medication up until 24 hours before those visits)."}

Exclusion criteria

• {"criterion_text":"- 1. Glycated haemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol) as measured by the central laboratory at screening.\n- 2. History of type 1 or type 2 diabetes mellitus as declared by the participant or reported in the medical records.\n- 3. 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 within CCI before screening.\n- 4. Any joint prosthesis or joint replacement in target knee.\n- 5. Arthroscopy or injections into target knee within the last 90 days prior to screening.\n- 6. Any other joint disease in target knee including gout and pseudogout."}

Primary endpoints

• {"endpoint_text":"- Relative change in body weight","definition_or_measurement_approach":"Relative change in body weight (endpoint text as provided); measurement approach not further specified in the record."}
• {"endpoint_text":"- Change in WOMAC Osteoarthritis Index NRS 3.1 (24-hour) (WOMAC) pain score","definition_or_measurement_approach":"Change in WOMAC Osteoarthritis Index NRS 3.1 (24-hour) pain score (measured using the WOMAC NRS 3.1 24-hour pain instrument as specified in the endpoint text)."}

Secondary endpoints

• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change in WOMAC physical function scorea","definition_or_measurement_approach":"Measured using the WOMAC physical function score (as specified in endpoint text)."}
• {"endpoint_text":"- Change in SF-36v2® Health Survey Acute (SF-36v2 Acute) physical functioning score","definition_or_measurement_approach":"Measured using the SF-36v2 Acute physical functioning score (as specified in endpoint text)."}
• {"endpoint_text":"- Change in body weight","definition_or_measurement_approach":"Change in body weight (endpoint text as provided); specific measurement details not provided in the record."}
• {"endpoint_text":"- Change in body mass index (BMI)","definition_or_measurement_approach":"Change in BMI (endpoint text as provided)."}
• {"endpoint_text":"- Change in WOMAC stiffness score","definition_or_measurement_approach":"Measured using the WOMAC stiffness score (as specified in endpoint text)."}
• {"endpoint_text":"- Change in WOMAC total score","definition_or_measurement_approach":"Measured using the WOMAC total score (as specified in endpoint text)."}
• {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change in waist circumference","definition_or_measurement_approach":"Change in waist circumference (endpoint text as provided)."}
• {"endpoint_text":"- Change in systolic blood pressure (SBP)","definition_or_measurement_approach":"Change in systolic blood pressure (SBP) (endpoint text as provided)."}
• {"endpoint_text":"- Change in diastolic blood pressure (DBP)","definition_or_measurement_approach":"Change in diastolic blood pressure (DBP) (endpoint text as provided)."}
• {"endpoint_text":"- Change in lipids: Total cholesterol High-density lipoprotein (HDL) cholesterol Low-density lipoprotein (LDL) cholesterol Very low-density lipoprotein (VLDL) cholesterol Non-HDL cholesterol Triglycerides","definition_or_measurement_approach":"Change in specified lipid parameters (total cholesterol, HDL, LDL, VLDL, non-HDL, triglycerides) as listed in the endpoint text."}
• {"endpoint_text":"- Change in high-sensitivity C-reactive protein (hsCRP)","definition_or_measurement_approach":"Change in hsCRP (endpoint text as provided)."}
• {"endpoint_text":"- Change in glycated haemoglobin (HbA1c)","definition_or_measurement_approach":"Change in HbA1c (endpoint text as provided)."}
• {"endpoint_text":"- Change in fasting plasma glucose (FPG)","definition_or_measurement_approach":"Change in fasting plasma glucose (FPG) (endpoint text as provided)."}
• {"endpoint_text":"- Use of allowed rescue analgesics during washout period (Yes/no)","definition_or_measurement_approach":"Yes/no use of allowed rescue analgesics during washout period (binary as specified)."}
• {"endpoint_text":"- Amount of allowed rescue analgesics used during washout period","definition_or_measurement_approach":"Amount of allowed rescue analgesics used during the washout period (endpoint text as provided)."}
• {"endpoint_text":"- Use of pain medication (Yes/No)","definition_or_measurement_approach":"Yes/No use of pain medication (endpoint text as provided)."}
• {"endpoint_text":"- Amount of pain medication used","definition_or_measurement_approach":"Amount of pain medication used (endpoint text as provided)."}
• {"endpoint_text":"- Change in pain medication (decrease/no change/increase)","definition_or_measurement_approach":"Change in pain medication categorized as decrease/no change/increase (endpoint text as provided)."}
• {"endpoint_text":"- Change in knee pain intensity (NRS)","definition_or_measurement_approach":"Change in knee pain intensity measured by NRS (endpoint text as provided)."}
• {"endpoint_text":"- Number of: Treatment Emergent Adverse Events (TEAEs) Treatment Emergent Serious Adverse Events (TESAEs) TEAEs leading to permanent treatment discontinuation","definition_or_measurement_approach":"Counts of TEAEs, TESAEs, and TEAEs leading to permanent treatment discontinuation (endpoint text as provided)."}

Methods

• Denmark: recruitment arrangements and recruitment posters (documents: k1_dk_nn9490-8294-recruitment-arrangements-english; recruitment posters and site materials) - channels include site posters and recruitment posters (Danish/English).
• Spain: recruitment arrangements including patient association poster, recruitment advertisement posters, social media campaign (reel), web design and online carousel materials (documents: k1_es_nn9490-8294-recruitment-arrangements; k2_es... patient association poster; reel-social-media-campaign; web-design). Channels include patient association posters, social media (reels), website/web design, and printed posters.
• Greece: recruitment arrangements and Greek recruitment advertisement (documents: k1_gr_nn9490-8294-recruitment-arrangements; k2-gr-nn9490-8294-recruitment-advertisement-greek) - channel: local recruitment advertisement/poster.
• Italy: recruitment and informed consent procedure and Italian recruitment advertisement (documents: k1_it_nn9490-8294-recruitment-and-informed-consent-procedure; k2-it-nn9490-8294-recruitment-advertisement-italian) - channel: recruitment advertisement/poster.
• Poland: recruitment arrangements and recruitment advertisement Polish (documents: k1_pl_nn9490-8294-recruitment-arrangements-polish; k2-pl-nn9490-8294-recruitment-advertisement-polish) - channel: recruitment advertisement/poster.
• Bulgaria: recruitment arrangements and recruitment advertisement Bulgarian (documents: k1_bg_nn9490-8294-recruitment-arrangements-bulgarian; k2-bg-nn9490-8294-recruitment-advertisement-bulgarian) - channel: recruitment advertisement/poster.
• Multiple countries: direct-to-patient materials and direct-to-patient/home-delivery subject information forms available (documents: l1_es-nn9490-8294-piic-direct-to-patient; l1_it-nn9490-8294-piic-home-delivery; direct-to-patient roles noted among third parties).

Bulgaria

Earliest CTIS Part Ii Submission Date

30-03-2026

Latest Decision Or Authorization Date

14-04-2026

Processing Time Days

15

Number Of Sites

6

Number Of Participants

35

Denmark

Earliest CTIS Part Ii Submission Date

26-03-2026

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

12

Number Of Sites

3

Number Of Participants

30

Greece

Earliest CTIS Part Ii Submission Date

22-01-2026

Latest Decision Or Authorization Date

08-04-2026

Processing Time Days

76

Number Of Sites

7

Number Of Participants

40

Italy

Earliest CTIS Part Ii Submission Date

18-12-2025

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

113

Number Of Sites

7

Number Of Participants

30

Spain

Earliest CTIS Part Ii Submission Date

03-03-2026

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

39

Number Of Sites

11

Number Of Participants

40

Poland

Earliest CTIS Part Ii Submission Date

18-12-2025

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

112

Number Of Sites

6

Number Of Participants

45

Primary sponsor

Full Name

Novo Nordisk A/S

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Imaging; Central Laboratory

Name

Iqvia Biotech Limited

Responsibilities

eCOA

Third parties

• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"eCOA","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Central Laboratory","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Marken Limited","duties_or_roles":"Direct to patient","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Roche Diabetes Care Inc.","duties_or_roles":"Blood Glucose Meter","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"Acquire and submit for central reading the Xray images of the target knee.","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Actigraph LLC","duties_or_roles":"Physical Activity Monitoring","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"CRF supplier and Global Safety Database supplier","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Greece","full_name":"Athens Medical Center S.A.","duties_or_roles":"Acquire and submit for central reading the Xray images of the target knee.","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Colorado Prevention Center","duties_or_roles":"Performance Test: 6-minute walk test (6MWT) and Performance Test: Sit to Stand","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"RTSM/IWRS supplier and RTSM/IWRS helpdesk","organisation_type":"Non-Pharmaceutical company"}