Clinical trial • Phase III • Endocrinology|Musculoskeletal

ZENAGAMTIDE for Overweight or obesity | Knee osteoarthritis

Phase III trial of ZENAGAMTIDE for Overweight or obesity | Knee osteoarthritis. Placebo-controlled. 180 participants.

Overview

Trial Therapeutic Area
Endocrinology|Musculoskeletal
Trial Disease
Overweight or obesity | Knee osteoarthritis
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme

Key dates

Initial CTIS Submission Date
03-12-2025
First CTIS Authorization Date
07-04-2026

Trial design

Placebo-controlled Phase III trial in Bulgaria, Denmark, Greece and others.

Comparator
Placebo
Target Sample Size
180

Eligibility

Recruits 180 No vulnerable populations selected; participants must be 18 years or older and provide informed consent..

Vulnerable Population
No vulnerable populations selected; participants must be 18 years or older and provide informed consent.

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 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.\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."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Relative change in body weight","definition_or_measurement_approach":"Relative change in body weight (measured as percent change from baseline in body weight)."}
  • {"endpoint_text":"- Change in WOMAC Osteoarthritis Index NRS 3.1 (24-hour) (WOMAC) pain score","definition_or_measurement_approach":"Measured using the WOMAC Osteoarthritis Index NRS 3.1 (24-hour) pain score (patient-reported numerical rating scale as per WOMAC instrument)."}

Secondary endpoints

  • {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
  • {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Change in WOMAC physical function score","definition_or_measurement_approach":"Measured using the WOMAC physical function subscale."}
  • {"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 (patient-reported questionnaire)."}
  • {"endpoint_text":"- Change in body weight","definition_or_measurement_approach":"Absolute change in body weight measured at study visits."}
  • {"endpoint_text":"- Change in body mass index (BMI)","definition_or_measurement_approach":"Change in BMI calculated from measured weight and height."}
  • {"endpoint_text":"- Change in WOMAC stiffness score","definition_or_measurement_approach":"Measured using the WOMAC stiffness subscale."}
  • {"endpoint_text":"- Change in WOMAC total score","definition_or_measurement_approach":"Measured using the total WOMAC score (sum of subscales)."}
  • {"endpoint_text":"- CCI","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Change in waist circumference","definition_or_measurement_approach":"Measured waist circumference at study visits."}
  • {"endpoint_text":"- Change in systolic blood pressure (SBP)","definition_or_measurement_approach":"Measured systolic blood pressure (mmHg) at study visits."}
  • {"endpoint_text":"- Change in diastolic blood pressure (DBP)","definition_or_measurement_approach":"Measured diastolic blood pressure (mmHg) at study visits."}
  • {"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 and Triglycerides","definition_or_measurement_approach":"Fasting lipid panel measured in central laboratory (total cholesterol, HDL, LDL, VLDL, non-HDL, triglycerides)."}
  • {"endpoint_text":"- Change in high-sensitivity C-reactive protein (hsCRP)","definition_or_measurement_approach":"Measured hsCRP in central laboratory."}
  • {"endpoint_text":"- Change in glycated haemoglobin (HbA1c)","definition_or_measurement_approach":"Measured HbA1c in central laboratory."}
  • {"endpoint_text":"- Change in fasting plasma glucose (FPG)","definition_or_measurement_approach":"Measured fasting plasma glucose in central laboratory."}
  • {"endpoint_text":"- Use of allowed rescue analgesics during washout period (Yes/no)","definition_or_measurement_approach":"Recorded as Yes/No per participant during washout period."}
  • {"endpoint_text":"- Amount of allowed rescue analgesics used during washout period","definition_or_measurement_approach":"Recorded quantity of rescue analgesic use during washout period."}
  • {"endpoint_text":"- Use of pain medication (Yes/No)","definition_or_measurement_approach":"Recorded as Yes/No for pain medication use."}
  • {"endpoint_text":"- Amount of pain medication used","definition_or_measurement_approach":"Recorded amount of pain medication used."}
  • {"endpoint_text":"- Change in pain medication (decrease/no change/increase)","definition_or_measurement_approach":"Categorical change recorded as decrease / no change / increase."}
  • {"endpoint_text":"- Change in knee pain intensity (NRS)","definition_or_measurement_approach":"Measured using Numerical Rating Scale (NRS) for knee pain intensity."}
  • {"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":"Safety endpoints counted as number of events (TEAEs, TESAEs, TEAEs leading to permanent discontinuation)."}

Recruitment

Registry Or Advocacy Recruitment
True, Patient association (unnamed)
Digital Remote Recruitment
True; recruitment materials include web adverts, reels, and online recruitment materials and direct-to-patient approaches (country-specific files for web/reel/online recruitment).
Planned Sample Size
180
Recruitment Window Months
26
Consent Approach
Informed consent is provided by the participant (age 18 years or above). Subject information and informed consent forms are available as documented L1 files in multiple languages (English and country-specific languages: Bulgarian, Danish/English materials, Greek, Italian, Spanish, Polish). Materials include participant information for adult participants and partner/male partner information where applicable.

Methods

  • Direct to patient (specified as a sponsor/third-party duty and in recruitment materials)
  • Posters at sites (country-specific recruitment posters listed for multiple countries)
  • Web recruitment / online adverts (recruitment-material-web and recruitment reels listed)
  • Recruitment advertisements (country-specific recruitment advertisement documents listed)
  • Patient association materials (patient-association-material-poster listed for Spain)
  • Home delivery / direct-to-patient drug delivery (documents and subject information mention home delivery / direct-to-patient)

Geography

Total Number Of Sites
47
Total Number Of Participants
220

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

Sites

Site Name
Medical Center D-R Atanasov EOOD
Contact Person Name
Lyubomir Atanasov
Contact Person Email
liubomir11@yahoo.com
Site Name
University Multiprofile Hospital For Active Treatment Saint Georgi EAD
Department Name
Clinic of rheumatology
Contact Person Name
Krasimir Iliev Kraev
Contact Person Email
dr.krasimir.kraev@gmail.com
Site Name
University Multiprofile Hospital For Active Treatment St. Ivan Rilski EAD
Department Name
Clinic of rheumatology
Contact Person Name
Vladimira Vasileva Boyadjieva
Site Name
Medical Center Excelsior OOD
Contact Person Name
Tzvetanka Petrova Petranova
Contact Person Email
dr_petranova@yahoo.com
Site Name
Uniteversity Muliprofile Hospital For Active Treatment Tsaritsa Yoanna-Isul EAD
Department Name
Clinic of orthopedics and traumatolog
Contact Person Name
Georgi Petrov Georgiev
Contact Person Email
georgievgp@yahoo.com
Site Name
Military Medical Academy
Department Name
Department of rheumatology
Contact Person Name
Boycho Alexandrov Oparanov
Contact Person Email
oparanov@abv.bg

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

Sites

Site Name
Region Hovedstaden
Contact Person Name
Henning Bliddal
Contact Person Email
Henning.Bliddal@frh.regionh.dk
Site Name
Region Midtjylland
Contact Person Name
Ellen-Margrethe Hauge
Contact Person Email
ellen.hauge@aarhus.rm.dk
Site Name
Sanos A/S
Contact Person Name
Marina Harutyunyan-Bønsager
Contact Person Email
mahau@regionsjaelland.dk

Greece

Earliest CTIS Part Ii Submission Date
18-12-2025
Latest Decision Or Authorization Date
08-04-2026
Processing Time Days
111
Number Of Sites
8
Number Of Participants
40

Sites

Site Name
University General Hospital Attikon General Hospital Of West Attica H Agia Varvara
Department Name
2nd Department of Internal medicine, research institute and Diabetes Center
Contact Person Name
Vaia Lambadiari
Contact Person Email
vlambad@otenet.gr
Site Name
NextHealth S.A.
Department Name
Department of Endocrinology, Metabolism & Diabetes
Contact Person Name
Maria Somali
Contact Person Email
somalimaria@hotmail.com
Site Name
Thermi Clinic S.A.
Department Name
Diabetes Department
Contact Person Name
Emmanouil Pagkalos
Contact Person Email
epagkalos@gmail.com
Site Name
Athens Medical Center S.A.
Department Name
Department of Internal Medicine & Metabolic Diseases
Contact Person Name
Gerasimos Karousos
Contact Person Email
gkarousosmd@gmail.com
Site Name
Laiko General Hospital Of Athens
Department Name
First Department of Propaedeutic Internal Medicine
Contact Person Name
Alexandros Kokkinos
Contact Person Email
rjd@otenet.gr
Site Name
Athens Medical Center S.A.
Department Name
Diabetes and Obesity Unit
Contact Person Name
Georgia Argyrakopoulou
Contact Person Email
gargyrakopoulou@gmail.com
Site Name
General Hospital Of Athens Alexandra
Department Name
Clinical Therapeutics
Contact Person Name
Theodora Psaltopoulou
Contact Person Email
tpsaltop@gmail.com
Site Name
Thermi Clinic S.A. (other site listed)

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
9
Number Of Participants
30

Sites

Site Name
Universita' Campus Bio-medico Di Roma
Contact Person Name
Dario Tuccinardi
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Contact Person Name
Fabrizio Pasanisi
Contact Person Email
pasanisi@unina.it
Site Name
Azienda Ospedaliero Universitaria Di Modena
Contact Person Name
Vincenzo Rochira
Contact Person Email
vincenzo.rochira@unimore.it
Site Name
Azienda Ospedaliero Universitaria Integrata Verona
Contact Person Name
Davide Gatti
Contact Person Email
davide.gatti@univr.it
Site Name
Azienda Sanitaria Universitaria Friuli Centrale
Contact Person Name
Fabio Vescini
Site Name
Istituto Auxologico Italiano
Contact Person Name
Simona Bertoli
Contact Person Email
simona.bertoli@unimi.it
Site Name
Policlinico San Donato S.p.A.
Contact Person Name
Alexis Malavazos
Site Name
Azienda Sanitaria Universitaria Friuli Centrale (other site listed)
Site Name
Additional Italian listed site

Spain

Earliest CTIS Part Ii Submission Date
03-03-2026
Latest Decision Or Authorization Date
10-04-2026
Processing Time Days
38
Number Of Sites
13
Number Of Participants
40

Sites

Site Name
Nuevas Tecnologias En Diabetes Y En Endocrinologia S.L. Profesional
Contact Person Name
Alberto Aliaga Verdugo
Contact Person Email
a.aliaga@ntde.es
Site Name
Hospital Quironsalud Malaga
Contact Person Name
José Manuel García Almeida
Contact Person Email
jgarciaalmeida@quironsalud.es
Site Name
Instituto Medico Quirurgico San Rafael S.A.
Contact Person Name
Alfonso Soto González
Contact Person Email
asotog30@outlook.es
Site Name
Consorcio Hospital General Universitario De Valencia
Contact Person Name
Carlos Sánchez Juan
Contact Person Email
carlos.sanchez@uv.es
Site Name
Hospital Hm Rosaleda Hm La Esperanza
Contact Person Name
Manuel Pombo Suárez
Contact Person Email
Manuel.pombo.suarez@cicec.es
Site Name
Hospital Universitario Infanta Sofía
Contact Person Name
José Antonio Balsa
Contact Person Email
jbalsa@salud.madrid.org
Site Name
Hospital Quironsalud Infanta Luisa
Contact Person Name
Margarita Rivas Fernández
Site Name
Hospital Universitario Marques De Valdecilla
Contact Person Name
Luis Alberto Vázquez Salvi
Contact Person Email
luisalberto.vazquez@scsalud.es
Site Name
Centro de Especialidades Hermanos Sangro/Hospital Gregorio Marañón
Contact Person Name
Marta Supervía
Site Name
Hospital Germans Trias I Pujol
Contact Person Name
Ana Silvia Pellitero Rodriguez
Site Name
Area Sanitaria De Ferrol
Contact Person Name
Diego Bellido Guerrero
Site Name
Additional Spanish listed site
Site Name
Additional Spanish listed site 2

Poland

Earliest CTIS Part Ii Submission Date
06-03-2026
Latest Decision Or Authorization Date
09-04-2026
Processing Time Days
34
Number Of Sites
8
Number Of Participants
45

Sites

Site Name
Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher
Department Name
Centrum Wsparcia Badań Klinicznych
Contact Person Name
Jakub Wroński
Contact Person Email
jakub.wronski@spartanska.pl
Site Name
Centermed Krakow Sp. z o.o.
Contact Person Name
Artur Gadek
Contact Person Email
drgadek@poczta.onet.pl
Site Name
Szpital Specjalistyczny Im. Ludwika Rydygiera W Krakowie Sp. z o.o.
Department Name
Oddział Ortopedii i Traumatologii Narządu Ruchu
Contact Person Name
Grzegorz Kwiatkowski
Site Name
Centrum Medyczne Intercor Sp. z o.o.
Contact Person Name
Roman Junik
Contact Person Email
intercor@farmepo.com
Site Name
Zdrowie Osteo-Medic S.C. Lidia i Artur Racewicz, Agnieszka i Jerzy Supronik
Contact Person Name
Jerzy Supronik
Contact Person Email
jerzy_supronik@op.pl
Site Name
Clinicmed Daniluk Nowak Sp. k.
Contact Person Name
Stefan Daniluk
Contact Person Email
daniluk@clinicmed.pl
Site Name
Additional Polish listed site 1
Site Name
Additional Polish listed site 2

Sponsor

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 (separate entries for imaging and central laboratory support)
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":"Marken Limited","duties_or_roles":"Direct to patient","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"RTSM/IWRS supplier and RTSM/IWRS helpdesk","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Central Laboratory","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"CRF supplier Global Safety Database supplier","organisation_type":"Non-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":"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 Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"eCOA","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Celerion Switzerland AG","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Roche Diabetes Care Inc.","duties_or_roles":"Blood Glucose Meter","organisation_type":"Pharmaceutical company"}
  • {"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"}

Investigational products

Investigational Product Name
NNC0487-0111 B 10141
Active Substance
ZENAGAMTIDE
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS
Route
SUBCUTANEOUS
Frequency
once-weekly
Investigational Product Name
NNC0487-0111 B 10142
Active Substance
ZENAGAMTIDE
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS
Route
SUBCUTANEOUS
Frequency
once-weekly
Investigational Product Name
NNC0487-0111 B 10143
Active Substance
ZENAGAMTIDE
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS
Route
SUBCUTANEOUS
Frequency
once-weekly
Investigational Product Name
NNC0487-0111 B 10144
Active Substance
ZENAGAMTIDE
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS
Route
SUBCUTANEOUS
Frequency
once-weekly
Investigational Product Name
NNC0487-0111 B 10145
Active Substance
ZENAGAMTIDE
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS
Route
SUBCUTANEOUS
Frequency
once-weekly
Investigational Product Name
NNC0487-0111 B 10146
Active Substance
ZENAGAMTIDE
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS
Route
SUBCUTANEOUS
Frequency
once-weekly
Investigational Product Name
Placebo
Modality
Other

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