Efficacy and Safety of KBP-336 in Obese Individuals with Osteoarthritis

Exclusion Criteria32

• Partial or complete joint replacement of either knee
• Target knee surgery or arthroscopy within 1 year prior to screening
• Diagnosis of OA resulting from trauma within the last 5 years
• Pain of the contralateral knee exceeding that of the target knee at the baseline visit, as measured by the WOMAC pain subscale
• Planned major surgery within the next 6 months
• Uncontrolled thyroid disease in the opinion of the Investigator based on medical history and laboratory results collected in screening
• Participant-reported weight loss >5% of body weight within the last 6 months of the screening visit
• Bariatric surgery within the last 12 months of the screening visit
• Current comorbid condition, other than OA, affecting target knee or systemic illness known to be significantly associated with arthritis or joint pathology affecting any joint, including but not necessarily limited to endocrinopathies, inflammatory, or autoimmune disease with significant joint involvement (e.g., Rheumatoid Arthritis); Seronegative Spondyloarthropathies (e.g. Ankylosing Spondylitis, Psoriasis arthritis, Reactive arthritis)
• Conditions significantly affecting joint and bone health, in the opinion of the Investigator should be excluded (including but not limited to atrophic or hypotrophic OA, subchondral insufficiency fracture, osteonecrosis, osteoporotic fractures, excessive malalignment of the knee or severe chondrocalcinosis)
• Active comorbid condition other than OA (e.g radicular back pain, bursitis, tendinitis) significantly affecting target knee pain reporting in the opinion of the investigator.
• A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15 at screening
• History of gout, or pseudogout, with high likelihood of flare up during trial participation that would require NSAID treatment, in the opinion of the investigator
• Hip dislocation and congenital hip dysplasia with degenerative joint disease should be excluded.
• Participation in any previous DACRA/amylin study
• History or presence of clinically significant neurological disease or psychiatric disorder in the opinion of the investigator
• Intra-articular injection of corticosteroids within 3 months or hyaluronic acid within 6 months of screening in the target knee or into any other major joint within 30 days prior to screening (for extended-release corticosteroid injections: within 6 months in target knee and 3 months into any other major joint).
• Systemic corticosteroid treatment for the treatment of musculoskeletal conditions of more than 14 days during the past 6 months prior to screening.
• Any pharmacological or non-pharmacological treatment primarily targeting OA started or changed during the 4 weeks prior to randomization or likely to be changed during the duration of the study
• Treatment with medication for obesity, including GLP-1 analogues, unless the dose of use has been stable for at least six months prior to screening
• Vitamin D deficiency defined as blood 25-OH D3 concentration ≤25 nmol/L. Vitamin D supplementation and subsequent rescreening is allowed
• Presence or history of clinically significant allergies, including relevant drug hypersensitivity or allergy
• Current malignancy or treatment for malignancy within the past five years, apart from resected basal cell carcinoma, squamous skin cell carcinoma, or resected cervical atypia or carcinoma in situ, unless affecting the target knee area.
• History of alcohol or drug abuse within 5 years prior to screening, in the opinion of the Investigator.
• Use of an investigational drug within 90 days prior to screening
• For women of childbearing potential:
• Pregnancy (i.e. positive serum pregnancy test at screening) or breastfeeding
• Failure to agree to practice a highly effective method of contraception (see Appendix 2), from enrolment up to at least 3 months after the study end
• For sexually active men with a female partner of childbearing potential:
• Failure to agree to ensure that their female partners use a highly effective method of contraception (see Appendix 2) from enrolment up to at least 3 months after the study end
• Failure to agree not to donate sperm throughout the study and at least 3 months after the study end
• Unsuitable for study participation for any reason in the opinion of the Investigator.