A Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects
Condition: Osteoarthritis
MeSH terms: Osteoarthritis
Intervention: SM04690; Placebo
Intervention MeSH terms: Lorecivivint
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 455.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Osteoarthritis; Samumed; SM04690

Summary:

      The purpose of this study is to assess the efficacy, safety, and tolerability of three
      different strengths of SM04690 injected in the target knee joint of moderately to severely
      symptomatic osteoarthritis (OA) subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and females between 40 and 80 years of age, inclusive, in general good health

          2. Ambulatory (single assistive devices such as canes allowed if needed less than 50% of
             the time, subjects requiring a walker are excluded)

          3. Established diagnosis of primary femorotibial OA in the target knee by standard
             American College of Rheumatology (ACR) criteria for at least 6 months (clinical AND
             radiographic criteria); if bilateral knee OA is present, the target knee is defined as
             the knee with greater pain at screening based on the subject's evaluation and the
             Investigator's clinical judgment

          4. Radiographic disease Stage 2 or 3 in the target knee according to the
             Kellgren-Lawrence grading of knee OA as assessed by independent central readers

          5. Screening pain visual analog scale (VAS) score of 30-80 mm (on a scale of 0-100 mm)
             for the target knee while on symptomatic oral treatment at screening (if the subject
             requires oral treatment)

          6. Total WOMAC score of 72-192 (out of 240) for the target knee while on symptomatic oral
             treatment at screening (if the subject requires oral treatment)

          7. 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.)

          8. Full understanding of the requirements of the study and willingness to comply with all
             study visits and assessments

          9. Subjects must have read and understood the informed consent form, and must have signed
             it prior to any study-related procedure being performed

         10. Subject's Day 1 visit must occur while enrollment into the study is open

        Exclusion Criteria:

          1. Women who are pregnant or lactating

          2. 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)

          3. Body mass index (BMI) >40

          4. Partial or complete joint replacement in the target knee

          5. Previous exposure to SM04690

          6. Major surgery (e.g., interventional arthroscopy) in the target knee within 52 weeks
             prior to any study injection

          7. Any planned or elective surgery during the study period

          8. Significant and clinically evident misalignment of the target knee that would impact
             subject function, as determined by the Investigator

          9. 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

         10. Clinically significant abnormal Screening Visit hematology values, blood chemistry
             values, HbA1c, or urinalysis values as determined by the investigator

         11. Any condition, including laboratory findings (not included in the Screening Visit
             laboratory tests) and findings in the medical history or in the pre-study assessments,
             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

         12. 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

         13. Other conditions that, in the opinion of the Investigator, could affect pain
             assessment of the target knee, including, but not limited to, symptomatic hip
             osteoarthritis and symptomatic degenerative disc disease

         14. Any diagnosed psychiatric condition that includes, but is not limited to, a history of
             mania, bipolar disorder, psychotic disorder, schizophrenia, major depressive disorder,
             or generalized anxiety disorder

         15. 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; the last date of participation in the trial, not the
             last date of receipt of investigational product, must be at least 12 weeks prior to
             Study Visit Day 1

         16. Treatment of the target knee with systemic or intra-articular corticosteroids (e.g.,
             methylprednisolone) within 8 weeks prior to Study Visit Day 1

         17. Viscosupplementation (e.g., hyaluronic acid) in the target knee within 24 weeks prior
             to Study Visit Day 1

         18. Effusion of the target knee clinically requiring aspiration within 12 weeks prior to
             Study Visit Day 1

         19. Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within
             4 weeks prior to Study Visit Day 1

         20. 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)

         21. Subjects taking prescription medications for OA who have not maintained a stable
             therapeutic regimen for a minimum of 12 weeks prior to Study Visit Day 1

         22. Subjects requiring the chronic use (i.e., regular and consistent use for ≥ 12 weeks)
             of the medications listed below within 12 weeks prior to Study Visit Day 1:

               1. Opioids, both oral (e.g., tramadol) or 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 inhaled, intranasal, and ophthalmic solutions

         23. 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 12 weeks prior to Study Visit Day 1. In addition, the
             following subjects will be excluded:

               1. Subjects with a baseline HbA1c >9

               2. Subjects with uncontrolled hypertension in the opinion of the investigator

               3. Subjects with symptomatic coronary artery disease in the opinion of the
                  investigator

         24. Subjects who have a current or pending disability claim, workers' compensation, or
             litigation(s) that may compromise response to treatment

         25. Subjects who are immediate family members (spouse, parent, child, or sibling;
             biological or legally adopted) of personnel directly affiliated with the study at the
             investigative site, or are directly affiliated with the study at the investigative
             site

         26. Subjects employed by Samumed, LLC, or any of its affiliates or development partners
             (that is, an employee, temporary contract worker, or designee) responsible for the
             conduct of the study