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

NCT06191848 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 75430
• Study Type: interventional
• Target: 352
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Obesity; Knee Osteoarthritis; Osteoarthritis, Knee

Keywords

Osteoarthritis; Obesity; Total knee replacement

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (16)

• Osteoarthritis Pain

  Baseline, Week 72

• Osteoarthritis Function

  Baseline, Week 72

• Osteoarthritis Stiffness

  Baseline, Week 72

• Percentage change in bodyweight

  Baseline, Week 72

• ≥5% body weight reduction

  Baseline, Week 72

Study Arms (2)

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

Drug: Tirzepatide

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Tirzepatide DRUG

Participants will receive tirzepatide subcutaneously

Tirzepatide

Placebo DRUG

Participants will receive placebo subcutaneously

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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 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

Sponsors & Collaborators

• University of Melbourne: lead
• Eli Lilly and Company: collaborator

Study Sites (4)

St Vincents Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

RECRUITING

Western Health

Melbourne, Victoria, 3011, Australia

RECRUITING

Austin Health-Repatriation Hospital

Melbourne, Victoria, 3084, Australia

RECRUITING

Eastern Health

Melbourne, Victoria, 3128, Australia

RECRUITING

MeSH Terms

Conditions

Obesity; Osteoarthritis, Knee; Osteoarthritis

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Michelle M Dowsey

  University of Melbourne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angela Cochrane

CONTACT

+61392312364; angela.cochrane@svha.org.au

Michelle M Dowsey

CONTACT

+61392313955; mmdowsey@unimelb.edu.au

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: January 5, 2024
• Study Start: November 19, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2037
• Last Updated: April 30, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary results publication. Data will be indefinitely available for requesting
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

AU (4)