A Study of Hyaluronate Injectable Viscosupplement for Treatment of Osteoarthritis of the Knee

Study Overview
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Brief Summary
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The study is a prospective, multi-center, randomized, three-arm, parallel group, clinical study to evaluate the superiority of 3 weekly intra-articular (IA) doses of 2 mL of Investigational hyaluronate as compared to placebo injected into the target knee for the treatment of pain in subjects with Osteoarthritis (OA).The safety and effectiveness of the investigational product will also be compared with Euflexxa.

Detailed Description
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The primary objective is to evaluate the safety and effectiveness of 3 weekly IA doses of 2 mL of hyaluronate viscosupplement as compared to placebo injected into the target knee for the treatment of pain in subjects with OA As secondary objectives, the study will evaluate the safety and effectiveness of 3 weekly IA doses of 2 mL of Viscosupplement as compared to Euflexxa injected into the target knee for the treatment of pain in subjects with OA. In addition, to assess the effect of Viscosupplement on pain, stiffness, and physical function of the target knee, as well as functional health and general well-being

Official Title
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A Double-Blind, Randomized, Study of the Effectiveness and Safety of Hyaluronate Injectable Viscosupplement for Treatment of Osteoarthritis of the Knee

Conditions
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Osteoarthritis

Intervention / Treatment
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* Device: Hyaluronate Injectable Viscosupplement
* Device: Euflexxa IA injection
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic OA of target knee confirmed by American College of Rheumatology Criteria Pain due to OA in target knee that had been present for at least 6 months, with a moderate to severe pain score of >50 mm recorded on a 100 mm Visual Analogue Scale (VAS) following a 50-foot walk Subject agrees to discontinue all pain medications for at least 7 days prior to start of study A bilateral standing anteroposterior x-ray confirming Grade 2 or 3 OA of the target knee Body mass index ≤40kg/m2 Able and willing to use only acetaminophen as the analgesic (rescue) study medication under the following conditions: acetaminophen dose is not to exceed 4 grams (4000mg)/day if the subject has known chronic liver disease, the maximum dose of acetaminophen is not to exceed 2 grams (2000 mg)/day subject must be able and willing to discontinue acetaminophen at least 24 hours prior to all study-specific visits Ability to perform procedures required of the pain index evaluations (unassisted walking for a distance of 50 feet on a flat surface and going up and down stairs) Agrees to use a highly effective contraception Able and willing to complete effectiveness and safety questionnaires and able to read and understand study instructions Exclusion Criteria: Any major injury to the target knee within the 12 months prior to the Screening and Enrollment Visit Any surgery to the target knee within the 12 months prior to the Screening and Enrollment Visit, Articular procedures such as transplants or ligament reconstruction to the target knee within 12 months prior to Screening and Enrollment Visit Inflammatory arthropathies such as rheumatoid arthritis, lupus arthropathy, or psoriatic arthritis Gout or calcium pyrophosphate diseases of the target knee that have flared within the 6 months prior to the Screening and Enrollment Visit X-ray findings of acute fractures, severe loss of bone density, avascular necrosis, and/or severe bone or joint deformity in the target knee Osteonecrosis of either knee Clinical signs and symptoms of active knee infection or crystal disease of the target knee Fibromyalgia, pes anserine bursitis, lumbar radiculopathy, and/or neurogenic or vascular claudication Significant anterior knee pain due to diagnosed isolated patella-femoral syndrome or chondromalacia in the target knee Significant target knee joint, infection or skin disorder infection within the 6 months prior to study enrollment Symptomatic OA of the hips, spine, or ankle, that interferes with the evaluation of the target knee Known hypersensitivity to acetaminophen or any of the study medications or their components Women of childbearing potential who are pregnant, nursing, or planning to become pregnant History of recurrent severe allergic or immune mediated reactions or other immune disorders Vascular insufficiency of lower limbs or peripheral neuropathy severe enough to interfere with the study evaluation Intra-arterial corticosteroid (investigational or marketed) in any joint within 3 months of Screening and Enrollment Visit Current treatment, or treatment within the 2 years prior to the Screening and Enrollment Visit, for any malignancy Active liver disease based on liver profile of aspartate aminotransferase, alanine aminotransferase, and conjugated bilirubin >2 times the upper limit of normal Renal insufficiency based on serum creatinine >2.0mg/dL Any intercurrent chronic disease or condition that might interfere with the completion of the study Current alcoholism and/or any known current addiction to pain medications Participation in any experimental device study within 6 months prior to the Screening and Enrollment Visit, or participation in an experimental drug study within 1 month prior to the Screening and Enrollment Visit.

Ages Eligible for Study
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Minimum Age: 40 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyaluronate Injectable Viscosupplement<br>Hyaluronate Injectable Viscosupplement (1% sodium hyaluronate). IA injection to the knee once weekly for 3 weeks | Device: Hyaluronate Injectable Viscosupplement<br>* Test product of a 1% sodium hyaluronate for injection<br>* Other names: 1% sodium hyaluronate;|
| Active Comparator: Euflexxa IA injection<br>Euflexxa IA injection to the knee once weekly for 3 weeks | Device: Euflexxa IA injection<br>* Brand product of a 1% sodium hyaluronate for injection<br>* Other names: 1% sodium hyaluronate;|
| Placebo Comparator: Placebo<br>Placebo (normal saline). IA injection to the knee once weekly for 3 weeks | Device: Placebo<br>* 0.9% sodium chloride, sterile<br>* Other names: Normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the WOMAC Pain Score in the Target Knee at Week 26 [Western Ontario and McMaster Universities Arthritis Index (WOMAC®)] | The primary effectiveness endpoint was the change from Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC®) pain score in the target knee at Week 26.The validated WOMAC was used to assess pain, stiffness, and physical function of the target knee.The range of pain score was 0 to 500 mm with higher scores for worse pain. | Baseline and 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pain Over Time From Baseline to Week 1, Week 6, Week 12 and Week 26 | The change from Baseline in the WOMAC pain score over time (baseline to Week 1, Week 6, Week 12 and Week 26) using Western Ontario and McMaster Universities Arthritis Index (WOMAC®)].The validated WOMAC was used to assess pain, stiffness, and physical function of the target knee.The range of pain score was 0 to 500 mm with higher scores for worse pain. | 26 weeks | 
| Change in Stiffness of the Knee After 26 Weeks as Measured by the WOMAC Pain Score in the Target Knee at Week 26 [Western Ontario and McMaster Universities Arthritis Index (WOMAC®)] | The change from baseline in the stiffness in the target knee at Week 26. The validated WOMAC was used to assess pain, stiffness, and physical function of the target knee.The range of stiffness score was 0 to 100 mm with higher scores for worse stiffness. | 26 weeks |