Safety and Bone Health Study of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

Inclusion Criteria

• Males and females between 40 and 80 years of age, inclusive, in general good health
• Ambulatory
• Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at Screening Visit 1 (clinical AND radiographic criteria); OA of the knee is not to be secondary to any rheumatologic conditions (e.g., rheumatoid arthritis)
• Pain compatible with OA of the knee(s) for at least 26 weeks prior to Screening Visit 1
• Primary source of pain throughout the body is due to OA in the target knee
• Daily OA knee pain diary average NRS intensity score ≥ 4 and ≤ 8 in the target knee on the 11-point (0-10) NRS scale for the 7 days immediately preceding Day 1
• Pain NRS scores recorded for the target knee on at least 4 out of the 7 days immediately preceding Day 1
• Daily OA knee pain diary average NRS intensity score 35
• Partial or complete joint replacement in either knee
• Currently requires:
• regular use (in the opinion of the Investigator) of ambulatory assistive devices (e.g., wheelchair, parallel bars, walker, canes, or crutches), or
• use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)
• Radiographic disease Stage 0, 1, or 4 in the target knee at Screening Visit 1 according to the Kellgren-Lawrence grading of knee OA as assessed by independent central readers
• Previous enrollment in a Samumed clinical trial investigating SM04690
• Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Screening Visit 1
• Any bone fracture(s) within 26 weeks prior to Screening Visit 1
• Any surgery scheduled during the study period. Non-surgical invasive procedures conducted for a diagnostic or therapeutic purpose scheduled during the study period are not prohibited.(refer to section 7.6)
• Significant and clinically evident misalignment of either knee that would impact subject function, as determined by the Investigator
• History of malignancy within the last 5 years; however, subjects with prior history of in situ basal or squamous cell skin cancer are eligible if completely excised. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years prior to Screening Visit 1
• Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator
• Any condition, including laboratory findings not included in the Screening Visit 2 laboratory tests and findings in the medical history or in the pre-study assessments, that, in the opinion of the Investigator, constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
• Comorbid conditions that could affect study endpoint assessments of the target knee, including, but not limited to, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, gout or pseudogout, and fibromyalgia
• Other conditions that, in the opinion of the Investigator, could affect study endpoint assessments of either knee, including, but not limited to, peripheral neuropathy (e.g., diabetic neuropathy), symptomatic hip osteoarthritis, symptomatic degenerative disc disease, and patellofemoral syndrome
• History of mania, bipolar disorder, psychotic disorder, schizophrenia, schizoaffective disorder, major depressive disorder, or generalized anxiety disorder
• Participation in a clinical research trial that included the receipt of an investigational product (IP) or any experimental therapeutic procedure within 26 weeks prior to Screening Visit 1, or planned participation in any such trial
• Treatment of the target knee with intra-articular glucocorticoids (e.g., methylprednisolone) within 12 weeks prior to Screening Visit 1
• Any intra-articular injection into the target knee with a therapeutic aim including, but not limited to, viscosupplementatio