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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: SM04690
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between 40 and 80 years of age, inclusive, in general good health Ambulatory (single assistive devices such as canes allowed if needed less than 50% of the time, subjects requiring a walker are excluded) 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 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 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) 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) Willingness to omit the following for 24 hours prior to all Study Visits, excluding the Screening Visit: Pain medications Medications or supplements for the treatment of OA 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 Subjects must have read and understood the informed consent form, and must have signed it prior to any study-related procedure being performed Subject's Day 1 visit must occur while enrollment into the study is open 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 52 weeks prior to any study injection Any planned or elective surgery during the study period Significant and clinically evident misalignment of the target knee that would impact subject function, 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 Clinically significant abnormal Screening Visit hematology values, blood chemistry values, HbA1c, or urinalysis values as determined by the investigator 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 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 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 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 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 Treatment of the target knee with systemic or intra-articular corticosteroids (e.g., methylprednisolone) within 8 weeks prior to Study Visit Day 1 Viscosupplementation (e.g., hyaluronic acid) in the target knee within 24 weeks prior to Study Visit Day 1 Effusion of the target knee clinically requiring aspiration within 12 weeks prior to Study Visit Day 1 Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within 4 weeks prior to Study Visit Day 1 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 12 weeks prior to Study Visit Day 1 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: Opioids, both oral (e.g., tramadol) or transdermal (e.g., fentanyl patches) formulations Centrally acting analgesics (e.g., duloxetine) Glucocorticoids (e.g., methylprednisolone) administered by any route, with exception of inhaled, 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 12 weeks prior to Study Visit Day 1. In addition, the following subjects will be excluded: Subjects with a baseline HbA1c >9 Subjects with uncontrolled hypertension in the opinion of the investigator Subjects with symptomatic coronary artery disease in the opinion of the investigator Subjects who have a current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment 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 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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.03 mg SM04690<br>Single intra-articular injection of SM04690 0.03 mg in 2 mL injectable suspension | Drug: SM04690<br> <br> |
| Experimental: 0.07 mg SM04690<br>Single intra-articular injection of SM04690 0.07 mg in 2 mL injectable suspension | Drug: SM04690<br> <br> |
| Experimental: 0.23 mg SM04690<br>Single intra-articular injection of SM04690 0.23 mg in 2 mL injectable suspension | Drug: SM04690<br> <br> |
| Placebo Comparator: Placebo<br>Single intra-articular injection of SM04690 0 mg in 2 mL phosphate buffered saline | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Osteoarthritis (OA) Pain in the Target Knee | Change from baseline OA pain in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 13. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Pain subscore is reported ranging from 0 to 100. | Baseline and Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline OA Pain in the Target Knee | Change from baseline OA pain in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 26. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Pain subscore is reported ranging from 0 to 100. | Baseline and Week 26 | 
| Change From Baseline OA Function in the Target Knee | Change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function) at Week 13. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore is reported ranging from 0 to 100. | Baseline and Week 13 | 
| Change From Baseline OA Function in the Target Knee | Change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function) at Week 26. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore is reported ranging from 0 to 100. | Baseline and Week 26 | 
| Change From Baseline OA Disease Activity as Assessed by the Patient | Change from baseline OA disease activity as assessed by the Patient Global Assessment at Week 13. The Patient Global Assessment was completed using a 100 mm visual analog scale (VAS) adapted from the Patient Assessment Form © 1999, American College of Rheumatology. The subject rated how well he/she was doing, considering all the ways in which illness and health conditions may affected him/her. The VAS scale was anchored by Very Well on the left (scored as 0) and Very Poorly on the right (scored as 100). Higher scores indicated poorer disease assessment by the subject. | Baseline and Week 13 | 
| Change From Baseline OA Disease Activity as Assessed by the Patient | Change from baseline OA disease activity as assessed by the Patient Global Assessment at Week 26. The Patient Global Assessment was completed using a 100 mm visual analog scale (VAS) adapted from the Patient Assessment Form © 1999, American College of Rheumatology. The subject rated how well he/she was doing, considering all the ways in which illness and health conditions may affected him/her. The VAS scale was anchored by Very Well on the left (scored as 0) and Very Poorly on the right (scored as 100). Higher scores indicated poorer disease assessment by the subject. | Baseline and Week 26 | 
| Change From Baseline in Medial Joint Space Width of Target Knee | Change from baseline in medial joint space width as documented by X-ray of the target knee at Week 26. | Baseline and Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Samumed, SM04690