Intervention: Adavivint
Trial phase: Phase 2
SMILES: CC(C)CC(=O)Nc1cncc(-c2ccc3[nH]nc(-c4nc5c(-c6cccc(F)c6)cncc5[nH]4)c3c2)c1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 106
Group description: Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle
Eligibility criteria:
Inclusion Criteria:

Ambulatory
Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at screening (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
Primary source of pain throughout the body is due to OA in the target knee
Willingness to use an electronic diary on a daily basis in the evening for the screening period and 24-week study duration
Negative drug test for opioids and drugs of abuse, except alcohol and marijuana, at screening
Subjects with depression or anxiety must be clinically stable for 12 weeks prior to screening, and, if on treatment for depression or anxiety, be on 12 weeks of stable therapy
Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
Subjects must have read and understood the informed consent form, and must have signed it prior to any study-related procedure being performed

Exclusion Criteria:

Women who are pregnant, lactating, or have a positive pregnancy result at screening
Women of child bearing potential who are sexually active and are not willing to use a highly effective method of birth control during the study period
Males who are sexually active and have a partner who is capable of becoming pregnant, neither of whom have had surgery to become sterilized or whom are not using a highly effective method of birth control
Body mass index (BMI) > 35
Partial or complete joint replacement in either knee
Currently requires regular use 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
Previous participation in a Samumed clinical trial investigating SM04690
Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to screening
Any planned surgery during the study period
History of malignancy within the last 5 years; however, subjects with prior history of in situ cancer or 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 any study injection
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
Any diagnosed psychiatric condition that includes, but is not limited to, a 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 or any experimental therapeutic procedure, or an observational research trial related to osteoarthritis within 8 weeks prior to any study injection, 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
Any intra-articular injection into the target knee with a therapeutic aim including, but not limited to, viscosupplementation (e.g., hyaluronic acid), platelet-rich plasma (PRP), and stem cell therapies within 24 weeks prior to screening; treatment of the target knee with intra-articular glucocorticoids greater than 12 weeks prior to screening is allowed
Treatment with systemic glucocorticoids greater than 10 mg prednisone or the equivalent per day within 4 weeks prior to screening
Effusion of the target knee clinically requiring aspiration within 12 weeks prior to screening
Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within 4 weeks prior to screening
Any known active infections, including urinary tract infection, upper respiratory tract infection, sinusitis, suspicion of intra-articular infection, hepatitis B or hepatitis C infection, and/or infections that may compromise the immune system such as human immunodeficiency virus (HIV) at study start
Use of centrally acting analgesics (e.g., duloxetine) within 12 weeks prior to screening
Use of anticonvulsants within 12 weeks prior to screening, unless used for seizure or migraine prophylaxis
Subjects requiring the usage of opioids >1x per week within 12 weeks prior to screening
Use of topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch) for the treatment of knee OA within 7 days of screening