A Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

This phase 2 study is a placebo-controlled, double-blind, parallel group study of four concentrations of SM04690 (0.03, 0.07, 0.15, and 0.23 mg per 2 mL injection) injected intraarticularly (IA) into the target knee joint of subjects with moderately to severely symptomatic osteoarthritis (OA). Based on previous studies of SM04690, key phenotypes of laterality (unilateral vs bilateral) as well as chronic pain (as measured by the Widespread Pain Index) were identified as confounding variables impacting the overall assessment of both radiologic and clinical efficacy outcomes. The design of SM04690-OA-04 is based upon previous study designs while assessing strategies to combat the confounding impact of laterality and chronic pain. To evaluate the effect of IA vehicle injection on patient-reported outcomes (PRO) such as pain, stiffness, and function in OA, this study also includes one cohort that receives a 2 mL IA injection of vehicle (placebo), and one cohort that receives a sham injection (i.e., a needle stick with 0 mL vehicle injected).


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