ObesityPhase 4STOP KNEE-OANCT06191848
Subcutaneous Tirzepatide Once-weekly in Patients With Obesity and Knee Osteoarthritis (STOP KNEE-OA)
A Phase 4 study testing Tirzepatide in people with Obesity and Knee Osteoarthritis, run by University of Melbourne at 4 sites in Australia.
Trial summary
This is a trial of tirzepatide in people with obesity and knee osteoarthritis. The main purpose of this study is to see if tirzepatide can reduce number of these participants who require a knee replacement. Participants will be randomized to take a weekly injection of tirzepatide or a placebo for a total of 72 weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obesity, Knee Osteoarthritis, Osteoarthritis, Knee
- What is being tested?
- Tirzepatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 352 participants
- Where
- 4 sitesAustralia
- Study dates
- 19 Nov 2024to May 2037
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a body mass index of ≥ to 30 kg/m2.
- Report one or more previous unsuccessful attempt to lose body weight via lifestyle modification.
- Have been deemed eligible to enter the waiting list for primary knee replacement for the treatment of osteoarthritis in the target joint by an orthopaedic surgeon at one of the participating study sites.
- Have moderate-to-severe knee osteoarthritis in the target joint, defined as a Kellgren-Lawrence grade two or greater.
- Be willing to and capable of learning how to self-inject the study drug and follow study procedures for the duration of the trial.
- Provide informed consent to study participation in line with the requirements of the human research ethics committee of the study site.
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- Female participants must:
- Not be currently pregnant or breastfeeding AND
- Not be of reproductive potential, defined as:
- Infertile due to surgical sterilization or congenital anomaly, OR
- Post-menopausal defined as:
- A woman over the age of 40 years with spontaneous cessation of menses for at least 12 consecutive months (in the absence of medications known to induce amenorrhea), with a follicle-stimulating hormone ≥40mIU/mL, and a negative pregnancy test prior to study entry, OR
- A woman over the age of 55 years with cessation of menses for at least 12 consecutive months (in the absence of medications known to induce amenorrhea), OR
- A woman over the age of 55 years that has commenced hormone replacement therapy after a documented diagnosis of menopause.
Who cannot join
- Participant will be ineligible for inclusion if they meet any of the following criteria:
- Have been deemed eligible to enter the waiting list for knee replacement in the contralateral knee by an orthopaedic surgeon at one of the participating study sites.
- Have used any prescription medications intended to promote weight loss (e.g., tirzepatide, liraglutide, semaglutide) in the three months prior to screening.
- Have previously undergone any surgical or endoscopic procedure intended to promote weight loss.
- Have been diagnosed with type 1 diabetes mellitus (T1DM) or T2DM
- Have laboratory evidence indicative of diabetes mellitus during screening.
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- Have personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Have an active malignancy (excluding basal or squamous cell skin cancer).
- Have had a transplanted organ or awaiting an organ transplant
- Have received chronic systemic glucocorticoid therapy (for more than 14 days) in prior 3 months or have a significant, active autoimmune abnormality (e.g., lupus or rheumatoid arthritis) that the study doctor deems likely to require systemic glucocorticoid therapy during the next 18 months.
- Have any other medical conditions, abnormal laboratory tests or concomitant medications that make them unsuitable for participation:
- Have a clinically significant gastric emptying abnormality.
- Have had a history of acute or chronic pancreatitis.
- Have obesity induced by other endocrinologic disorders
- Have an unstable psychiatric disorder
- Have a Patient Health Questionnaire (PHQ-9) score of >15 during screening
- Have been deemed by the study doctor to be actively suicidal,
- Have answered "yes" to questions 4 or 5 on the "Suicidal Ideation" section of the Columbia-Suicide Severity Rating Scale (C-SSRS) during screening, OR
- Have answered yes to any questions in the "Suicidal Behaviour" section of the C-SSRS during screening. AND
- The behaviour or ideation occurred in the last month
- Have uncontrolled hypertension (systolic blood pressure above or equal to 160 mmHg and/or diastolic blood pressure above or equal to 100 mmHg)
- Have had within the past 6 months prior to randomisation any of the following: acute myocardial infarction, cerebrovascular accident, unstable angina, or hospitalisation due to congestive cardiac failure (are also exclusion criteria for elective knee replacement)
- Have severe renal impairment defined as an eGFR <30 mL/min/1.73 m2 at screening visit.
- Have thyroid-stimulating hormone outside of the range of 0.4 to 6.0 mIU/L at screening visit
- Have acute or chronic hepatitis or abnormal liver function tests as measured by either alanine aminotransferase or alkaline phosphatase >200 IU.
- Have any other known contraindication to any glucagon-like peptide-1 receptor agonists.
- Are study site personnel, or immediate family of a member of the study site.
- Have been enrolled in any other study of an investigational product within the past ninety days or are currently enrolled in such a study.
Trial locations and contacts
4 sites in 1 country.
Australia4 sites
St Vincents Hospital Melbourne
Fitzroy, Victoria, 3065
Western Health
Melbourne, Victoria, 3011
Austin Health-Repatriation Hospital
Melbourne, Victoria, 3084
Eastern Health
Melbourne, Victoria, 3128
About this study
Official title: Effect of Subcutaneous Tirzepatide Once-weekly in Patients With Obesity and Knee Osteoarthritis (STOP KNEE-OA): A Randomized, Double-Blind, Placebo-Controlled Trial
This is a trial of tirzepatide in people with obesity and knee osteoarthritis. The main purpose of this study is to see if tirzepatide can reduce number of these participants who require a knee replacement. Participants will be randomized to take a weekly injection of tirzepatide or a placebo for a total of 72 weeks.
- Conditions
- Obesity, Knee Osteoarthritis, Osteoarthritis, Knee
- Being tested
- Tirzepatide, Placebo
- Keywords
- Osteoarthritis, Obesity, Total knee replacement
- Medical subject headings
- Obesity, Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
Participants will receive tirzepatide subcutaneously
PlaceboDrug
Participants will receive placebo subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| Tirzepatide | Experimental | Drug: Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1receptor (GLP1R) agonist Dose: Tirzepatide will be initiated at 2.5mg once weekly, with the dose increasing by a further 2.5mg every four weeks until the target weekly dose of 15mg is achieved (or participants reach a lower maximum tolerated dose of 5mg or 10mg).
Duration: 72-weeks Mode: subcutaneous Receives: Drug: Tirzepatide |
| Placebo | Placebo comparator | Drug: Placebo Dose: once-weekly Duration: 72 weeks Mode: subcutaneous Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients who undergo knee replacement in the target joint
Percentage of patients who undergo knee replacement in the target joint
Measured: within 72 weeks of randomization
Secondary outcomes (16)
Osteoarthritis Pain
Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. The WOMAC Pain subscale has 5-items, with a possible score range of 0-20, with higher scores indicating worse pain.
Measured: Baseline, Week 72
Osteoarthritis Function
Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Function Subscale Score. The WOMAC Function subscale has 17-items, with a possible range of 0-68, with higher scores indicating worse functional impairment.
Measured: Baseline, Week 72
Osteoarthritis Stiffness
Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score. The WOMAC Stiffness subscale has 2-items, with a possible range of 0-8, with higher score indicating worse stiffness.
Measured: Baseline, Week 72
Percentage change in bodyweight
Mean percentage change in body weight at 72 weeks after randomization
Measured: Baseline, Week 72
≥5% body weight reduction
Percentage of participants with ≥5% body weight reduction at 72 weeks after randomization
Measured: Baseline, Week 72
≥10% body weight reduction
Percentage of participants with ≥10% body weight reduction at 72 weeks after randomization
Measured: Baseline, Week 72
≥20% body weight reduction
Percentage of participants with ≥20% body weight reduction at 72 weeks after randomization
Measured: Baseline, Week 72
Physical Health
Mean change in the 36-item Short Form (SF-36) Physical Component Summary at 72 weeks after randomization. The SF-36 Physical Component Summary, a lower score indicates poorer physical health.
Measured: Baseline, Week 72
Mental Health
Mean change in the 36-item Short Form Survey (SF-36) Mental Component Summary at 72 weeks after randomization. For the SF-36 Mental Component Summary, a lower score indicates poorer mental health.
Measured: Baseline, Week 72
Physical Activity
Mean change in Physical Activity Scale for the Elderly (PASE) score at 72 weeks after randomization. The PASE has 12-items with a total score range from 0-400 or more, with higher scores indicating greater physical activity.
Measured: Baseline, Week 72
Non-opioid prescription pain medication use
Proportion of participants reporting use of non-opioid prescription analgesics between 68-72 weeks after randomization
Measured: Baseline, between 68-72 weeks
Opioid prescription pain medication use
Proportion of participants reporting use of prescription opioid analgesics between 68-72 weeks after randomization
Measured: Baseline, between 68-72 weeks
Mean change in use of prescription opioid pain medication
Mean change in prescription opioids dose at 72 weeks after randomization
Measured: Baseline, between 68-72 weeks
Participant willingness to undergo knee replacement surgery
Proportion of patients who undergo knee replacement in the target joint within 72 weeks of randomization or re-enter the waiting list within 72 weeks of randomization.
Measured: within the 72 weeks since randomization
Long-term (5-year) progression to knee replacement
Percentage of patients who undergo knee replacement in the target joint within 5-years
Measured: within 260 weeks of randomization
Long-term (10-year) progression to knee replacement
Percentage of patients who undergo knee replacement in the target joint within 10-years
Measured: within 520 weeks of randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2024
- Study start19 Nov 2024
- Primary completionMay 2027 (estimated)
- Study completionMay 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 352 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Melbourne
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- Michelle M Dowsey, Principal investigator, University of Melbourne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06191848
- Sponsor's protocol ID
- 75430
- Acronym
- STOP KNEE-OA
- Status last verified
- Jun 2026
- First submitted
- 18 Dec 2023
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval by the principal investigator of a research proposal and a signed data sharing agreement.
Publications
Ursini F, Ciaffi J, Caporali R. If the evidence is there, why are GLP-1 receptor agonists not on-label for hip and knee osteoarthritis in overweight patients? RMD Open. 2025 Sep 23;11(3):e006025. doi: 10.1136/rmdopen-2025-006025.
PubMed 40992788