Phase 1, Dose Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SM04690 in Moderate to Severe Knee Osteoarthritis (OA)

Inclusion Criteria:

- Diagnosed with primary OA in target knee by American College of Rheumatology (ACR)
criteria

- Screening pain criteria sufficient as assessed by WOMAC and VAS scores

- Ability to read and understand the informed consent

Exclusion Criteria:

- Women who are pregnant or lactating or child bearing potential, men must use a
barrier method of contraception

- Any condition, including laboratory findings, 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

- Body mass index >40

- Major knee surgery in the target knee within 12 months prior to study or planned
surgery during the study period

- History of malignancy within the last 5 years

- Participation in a clinical research trial within 12 weeks prior

- Treatment of the target knee with intra-articular steroids within 2 months or
hyaluronic acid derivatives within 6 months

- Effusion of the target knee requiring aspiration within 3 months

- Use of electrotherapy or acupuncture for OA within 4 weeks

- Significant and clinically evident misalignment of the target knee

- Any known active infections

- Any chronic condition that has not been well controlled for a minimum of 3 months