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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06191848




Registration number
NCT06191848
Ethics application status
Date submitted
18/12/2023
Date registered
5/01/2024

Titles & IDs
Public title
Subcutaneous Tirzepatide Once-weekly in Patients With Obesity and Knee Osteoarthritis (STOP KNEE-OA)
Scientific title
Effect of Subcutaneous Tirzepatide Once-weekly in Patients With Obesity and Knee Osteoarthritis (STOP KNEE-OA): A Randomized, Double-Blind, Placebo-Controlled Trial
Secondary ID [1] 0 0
75430
Universal Trial Number (UTN)
Trial acronym
STOP KNEE-OA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 0 0
Knee Osteoarthritis 0 0
Osteoarthritis, Knee 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Diet and Nutrition 0 0 0 0
Obesity
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tirzepatide
Treatment: Drugs - Placebo

Experimental: Tirzepatide - 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

Placebo comparator: Placebo - Drug: Placebo Dose: once-weekly Duration: 72 weeks Mode: subcutaneous


Treatment: Drugs: Tirzepatide
Participants will receive tirzepatide subcutaneously

Treatment: Drugs: Placebo
Participants will receive placebo subcutaneously
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of patients who undergo knee replacement in the target joint
Timepoint [1] 0 0
within 72 weeks of randomization
Secondary outcome [1] 0 0
Osteoarthritis Pain
Timepoint [1] 0 0
Baseline, Week 72
Secondary outcome [2] 0 0
Osteoarthritis Function
Timepoint [2] 0 0
Baseline, Week 72
Secondary outcome [3] 0 0
Osteoarthritis Stiffness
Timepoint [3] 0 0
Baseline, Week 72
Secondary outcome [4] 0 0
Percentage change in bodyweight
Timepoint [4] 0 0
Baseline, Week 72
Secondary outcome [5] 0 0
=5% body weight reduction
Timepoint [5] 0 0
Baseline, Week 72
Secondary outcome [6] 0 0
=10% body weight reduction
Timepoint [6] 0 0
Baseline, Week 72
Secondary outcome [7] 0 0
=20% body weight reduction
Timepoint [7] 0 0
Baseline, Week 72
Secondary outcome [8] 0 0
Physical Health
Timepoint [8] 0 0
Baseline, Week 72
Secondary outcome [9] 0 0
Mental Health
Timepoint [9] 0 0
Baseline, Week 72
Secondary outcome [10] 0 0
Physical Activity
Timepoint [10] 0 0
Baseline, Week 72
Secondary outcome [11] 0 0
Non-opioid prescription pain medication use
Timepoint [11] 0 0
Baseline, between 68-72 weeks
Secondary outcome [12] 0 0
Opioid prescription pain medication use
Timepoint [12] 0 0
Baseline, between 68-72 weeks
Secondary outcome [13] 0 0
Mean change in use of prescription opioid pain medication
Timepoint [13] 0 0
Baseline, between 68-72 weeks
Secondary outcome [14] 0 0
Participant willingness to undergo knee replacement surgery
Timepoint [14] 0 0
within the 72 weeks since randomization
Secondary outcome [15] 0 0
Long-term (5-year) progression to knee replacement
Timepoint [15] 0 0
within 260 weeks of randomization
Secondary outcome [16] 0 0
Long-term (10-year) progression to knee replacement
Timepoint [16] 0 0
within 520 weeks of randomization

Eligibility
Key inclusion criteria
* Have a body mass index of = 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.
* 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.

Female participants must either:

• 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.

OR

• Be of reproductive potential, and:

* Test negative for pregnancy on the initial screening visit via a serum pregnancy test, AND
* Use at least two effective forms of contraception, if sexually active, for the duration of the trial and until one month after the last injection of the study drug AND
* Not be breastfeeding.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion 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.
* 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 evidence of a significant, active autoimmune abnormality (e.g., lupus or rheumatoid arthritis)
* 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 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 renal impairment as measured by a serum Creatinine of =0.3 mg/dL (=26.5 µmol/L) 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 a calcitonin level at Visit 1 of: =20 ng/L with eGFR =60 mL/min/1.73 m2, or =35 ng/L with eGFR <60 mL/min/1.73 m2.
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/05/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2037
Actual
Sample size
Target
352
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy

Funding & Sponsors
Primary sponsor type
Other
Name
University of Melbourne
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michelle M Dowsey
Address 0 0
University of Melbourne
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Angela Cochrane
Address 0 0
Country 0 0
Phone 0 0
+61392312364
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Data are available 6 months after the primary results publication. Data will be indefinitely available for requesting
Available to whom?
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06191848