Subcutaneous Tirzepatide Once-weekly in Patients With Obesity and Knee Osteoarthritis (STOP KNEE-OA)

Obesity Clinical Trial

— STOP KNEE-OA  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06191848
• Other study ID #: 75430
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: May 2024
• Est. completion date: May 2037

Study information

• Verified date: January 2024
• Source: University of Melbourne
• Contact: Angela Cochrane
• Phone: +61392312364
• Email: angela.cochrane[@]svha.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 352
• Est. completion date: May 2037
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Obesity
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Tirzepatide
Participants will receive tirzepatide subcutaneously
• Placebo
Participants will receive placebo subcutaneously

Locations

Country	Name	City	State
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria

Sponsors (2)

Lead Sponsor	Collaborator
University of Melbourne	Eli Lilly and Company

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients who undergo knee replacement in the target joint	Percentage of patients who undergo knee replacement in the target joint	within 72 weeks of randomization
Secondary	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.	Baseline, Week 72
Secondary	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.	Baseline, Week 72
Secondary	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.	Baseline, Week 72
Secondary	Percentage change in bodyweight	Mean percentage change in body weight at 72 weeks after randomization	Baseline, Week 72
Secondary	=5% body weight reduction	Percentage of participants with =5% body weight reduction at 72 weeks after randomization	Baseline, Week 72
Secondary	=10% body weight reduction	Percentage of participants with =10% body weight reduction at 72 weeks after randomization	Baseline, Week 72
Secondary	=20% body weight reduction	Percentage of participants with =20% body weight reduction at 72 weeks after randomization	Baseline, Week 72
Secondary	Physical Health	Mean change in the 12-item Short Form (SF-12) Physical Component Summary at 72 weeks after randomization. The SF-12 Physical Component Summary has a score range of 24.00-56.58, with a lower score indicating poorer physical health.	Baseline, Week 72
Secondary	Mental Health	Mean change in the 12-item Short Form Survey (SF-12) Mental Component Summary at 72 weeks after randomization. The SF-12 Mental Component Summary has a score range of 19.06-60.76, with a lower score indicating poorer mental health.	Baseline, Week 72
Secondary	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.	Baseline, Week 72
Secondary	Non-opioid prescription pain medication use	Proportion of participants reporting use of non-opioid prescription analgesics between 68-72 weeks after randomization	Baseline, between 68-72 weeks
Secondary	Opioid prescription pain medication use	Proportion of participants reporting use of prescription opioid analgesics between 68-72 weeks after randomization	Baseline, between 68-72 weeks
Secondary	Mean change in use of prescription opioid pain medication	Mean change in prescription opioids dose at 72 weeks after randomization	Baseline, between 68-72 weeks
Secondary	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.	within the 72 weeks since randomization
Secondary	Long-term (5-year) progression to knee replacement	Percentage of patients who undergo knee replacement in the target joint within 5-years	within 260 weeks of randomization
Secondary	Long-term (10-year) progression to knee replacement	Percentage of patients who undergo knee replacement in the target joint within 10-years	within 520 weeks of randomization