Patient-Reported and Radiographic Outcomes in Evaluating Lorecivivint (SM04690) for the Treatment of Knee Osteoarthritis

Inclusion Criteria

• Males and females between 40 and 80 years of age, inclusive, in general good health apart from their knee OA
• Ambulatory (single assistive devices such as canes allowed if needed less than 50% of the time, subjects requiring a walker are excluded)
• Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at the Screening Visit (clinical AND radiographic criteria); OA of the knee is not to be secondary to any rheumatologic conditions (e.g., rheumatoid arthritis)
• mJSW by radiograph between 1.5 and 4 mm, inclusive, in the target knee within 12 weeks of the Screening Visit as assessed by independent central readers
• Radiographic disease Stage 2 or 3 in the target knee within 12 weeks of the Screening Visit according to the Kellgren-Lawrence (KL) grading of knee OA as assessed by independent central readers
• Pain compatible with OA of the knee(s) for at least 26 weeks prior to the Screening Visit
• Primary source of pain throughout the body is due to OA in the target knee
• Body mass index (BMI) ≤ 40 kg/m2 at the Screening Visit
• Widespread Pain Index (WPI) score of ≤ 4 and a Symptom Severity Question 2 (SSQ2) score of ≤ 2 at the Screening Visit and Day 1
• Pain NRS scores recorded for the target knee on at least 4 out of the 7 days immediately preceding Day 1
• Pain NRS scores recorded for the nontarget knee on at least 4 out of the 7 days immediately preceding Day 1
• 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
• Daily OA knee pain diary average NRS intensity score 10°, valgus > 10°) by radiograph within 12 weeks of the Screening Visit as assessed by independent central readers
• Partial or complete joint replacement in either knee
• Currently requires use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)
• Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Day 1
• Intra-articular (IA) injection into the target knee with a therapeutic aim including, but not limited to, hyaluronic acid, platelet-rich plasma (PRP),and stem cell therapies within 26 weeks prior to Day 1, or IA glucocorticoids within 12 weeks prior to Day 1
• Effusion of the target knee clinically requiring aspiration within 12 weeks prior to Day 1
• Use of electrotherapy, acupuncture, physical therapy, therapeutic ultrasound, and/or chiropractic treatments for knee OA within 4 weeks prior to Day 1
• Any bone fracture(s) within 26 weeks prior to the Screening Visit
• Previous treatment with SM04690
• Subjects who have previously failed screening on this protocol and fail to meet rescreening criteria
• 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 the Screening Visit, or planned participation in any such trial
• Treatment with systemic (oral, intramuscular, or intravenous) glucocorticoids ≥10 mg prednisone or the equivalent per day within 4 weeks prior to Day 1, or subjects on 1x per week within 12 weeks prior to Day 1
• Topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch) used for the treatment of knee OA within 7 days of Day 1
• Planned surgery scheduled during the study period, not including non-surgical invasive procedures conducted for a diagnostic or therapeutic purpose scheduled during the study period
• History of malignancy within the last 5 years, not including subjects with prior history of adequately treated in situ cervical cancer or basal or squamous cell skin cancer
• Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator
• Any condition, that, in the opinion of the Investigator, constitutes a risk or