A Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects

Inclusion Criteria:

- Established diagnosis of primary femorotibial OA in the target knee for at least 6
months (clinical and radiographic [x-ray] criteria)

- Radiographic [x-ray] disease Stage 2 or 3 in the target knee according to the
Kellgren-Lawrence grading of knee OA

- Screening pain visual analog scale (VAS) score in the required range for the target
knee while on oral symptomatic treatment (if required) at study start

- Total WOMAC score in the required range for the target knee while on symptomatic oral
treatment (if required) at study start

- Willingness to omit the following for 24 hours prior to all Study Visits, excluding
the Screening Visit:

1. Pain medications

2. Medications or supplements for the treatment of OA

3. Participation in a formalized in-office and/or supervised OA disease program
(e.g., a prescribed patient education program, physiotherapy, etc.)

- Full understanding of the requirements of the study and willingness to comply with all
study visits and assessments

Exclusion Criteria:

- Women who are pregnant or lactating

- Women of childbearing potential (i.e., who are not surgically sterile or
postmenopausal as defined by no menstrual periods for 12 consecutive months and no
other biological or physiological cause for amenorrhea can be identified); males who
are sexually active and have a partner who is capable of becoming pregnant, neither of
which have had surgery to become sterilized, who are not using an effective method of
birth control (e.g., surgically-implanted hormonal therapy, intrauterine devices or
oral birth control with barrier method)

- Body mass index (BMI) >40

- Partial or complete joint replacement in the target knee

- Previous exposure to SM04690

- Major surgery (e.g., interventional arthroscopy) in the target knee within 12 months
prior to any study injection

- Any planned or elective surgery during the study period

- Significant and clinically evident misalignment of the target knee, as determined by
the Investigator

- 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. 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 pain assessment of the target knee, including,
but not limited to, inflammatory rheumatic conditions such as rheumatoid arthritis,
psoriatic arthritis, systemic lupus erythematosus, diabetic neuropathy, pseudogout,
gout, and fibromyalgia

- Participation in a clinical research trial that included the receipt of an
investigational product or any experimental therapeutic procedure within 12 weeks
prior to any study injection

- Treatment of the target knee with systemic or intra-articular corticosteroids (e.g.,
methylprednisolone) within 2 months prior to study start

- Viscosupplementation (e.g., hyaluronic acid) in the target knee within 6 months prior
to study start

- Effusion of the target knee requiring aspiration within 3 months prior to study start

- Use of electrotherapy or acupuncture for OA within 4 weeks prior to study start

- Any known active infections, including 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)

- Subjects taking prescription medications for OA who have not maintained a stable
therapeutic regimen for a minimum of 3 months prior to study start

- Subjects requiring the chronic use of the following medications:

1. Opioids, both oral (e.g., tramadol) and transdermal (e.g., fentanyl patches)
formulations

2. Centrally acting analgesics (e.g., duloxetine)

3. Glucocorticoids (e.g., methylprednisolone) administered by any route, with
exception of intranasal and ophthalmic solutions

- Any chronic condition that has not been well controlled or subjects with a chronic
condition who have not maintained a stable therapeutic regimen of a prescription
therapy for a minimum of 3 months prior to study start