Obesity or Overweight
Conditions
Interventions
Orforglipron MTD:Maximum tolerated dose of Orforglipron
Placebo:Placebo
Sponsors
Huashan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Participant must be>=18 years of age or the legal age of consent in the jurisdiction in which the study is taking place at the time of screening (Visit 1). 2.Have a BMI>=27 kg/m^2 at screening (Visit 1). 3.Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight. 4.Have a WOMAC pain subscale (NRS 0 to10) score of>=4 and 12 weeks prior to screening (Visit 1), and presence of index knee pain for >15 days over the previous month based on participant report or medical history at screening (Visit 1). 6.Have an index knee X-ray at screening (between Visit 1 and Visit 2) read by the central radiology reviewer consistent with a diagnosis of knee OA based on American College of Rheumatology criteria with moderate radiographic changes (Kellgren-Lawrence Grade 2 or 3). 7.Have at least 1 of the following: Age >50 years ; Morning stiffness in the index knee less than 30 minutes in duration, and Crepitus in the index knee. 8.Are willing to discontinue all medications taken for chronic pain conditions, except allowed concomitant pain medication permitted per protocol in Section 6.9.2.2, for the duration of the study. 9.Individuals assigned male at birth and assigned female at birth may participate in this study.Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. For the contraception requirements of this protocol, see Section 10.4. 10.Capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 11.Are reliable and willing to make themselves available for the duration of the study, attend required study visits, and are willing and able to follow study procedures as required, such as maintain an electronic study diary, and complete required questionnaires.
Exclusion criteria
Exclusion criteria: 1.Have a self-reported or documented change in body weight >5 kg (11 pounds) within 90 days prior to screening (Visit 1). 2.Have a prior or planned surgical treatment for obesity Exception: The following are allowed if performed >1 year before screening (Visit 1) liposuction; cryolipolysis, or abdominoplasty. 3.Have a prior or planned endoscopic, for example, mucosal ablation or gastric artery embolization, and/or device-based, for example, lap band, intragastric balloon, or duodenal-jejunal endoluminal liner, therapy for obesity. Exception: Prior device-based therapy is acceptable if device removal was more than 6 months prior to screening (Visit 1). 4.Have obesity induced by other endocrinologic disorders (for example, Cushing Syndrome) or diagnosed monogenetic or syndromic forms of obesity, for example, Melanocortin 4 Receptor deficiency or Prader-Willi Syndrome. 5.In the judgment of the investigator, there is a condition that could confound the participant’s assessment of their index knee pain, including, but not limited to, pain in any other area of the lower extremities or back that is equal to or greater than the index knee pain, and pain from another location with radiation to the knee, for example, hip pain referred to the knee, radicular pain. 6.Have clinical signs and symptoms of active knee infection or crystal disease of the index knee within 30 days of screening (Visit 1), or any other active joint disease in the target knee other than OA that may confound assessment. 7.Have a history of other potentially causative and/or confounding conditions, including Reiter’s Syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis, amyloidosis, or fibromyalgia. 8.Have radiographic evidence of any potentially causative and/or confounding conditions at screening as determined by the central radiology reviewer, including, but not limited to, excessive malalignment of the knee, other arthropathies, systemic metabolic bone disease, tumor lesions, joint infection, and fracture. 9.Have an unstable joint such as a torn anterior cruciate ligament or recent trauma in either knee, within 12 months of screening (Visit 1). 10.Intramuscular or oral corticosteroids (investigational or marketed) within 30 days of screening (Visit 1). 11.Intra-articular corticosteroid (investigational or marketed) in any joint within 90 days of screening (Visit 1). 12.Intra-articular hyaluronic acid (investigational or marketed) in the index knee within 6 months of screening (Visit 1). 13.Procedure intended to produce sustained sensory loss in the index knee, for example ablation techniques, within 6 months of screening (Visit 1). 14.Any other intra-articular investigational drug or biologic use within 6 months of screening (Visit 1). 15.Prior arthroscopy of the index knee within 12 months of screening (Visit 1). 16.Prior joint replacement in the index knee. 17.Planned or anticipated surgery of the index knee or any other surgery that would require use of a restricted medication during the study period. 18.Have an intolerance, hypersensitivity, or contraindication to both acetaminophen/paracetamol and ibuprofen or any of their excipients. 19.Have T1D, T2D or any other type of diabetes, history of ketoacidosis, or hyperosmolar state/coma. 20.Have central laboratory evidence diagnostic of diabetes at screening (Visit 1), indicated by 1 or more of the following criteria: HbA1c >=6.5%
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| From baseline to Week 72:change in the WOMAC Pain subscale score; | — |
Countries
China
Contacts
Public ContactWeiguo Wan
Huashan Hospital, Fudan University
Outcome results
None listed