Safety and Effectiveness of Monovisc® Injection for Osteoarthritis of the Knee

Study Overview
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Brief Summary
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The purpose of this study is to determine whether intra-articular injection of Monovisc® hyaluronic acid provides symptomatic relief of osteoarthritis of the knee.

Detailed Description
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This randomized, double-blind, placebo controlled prospective study will assess the safety and effectiveness of a single intra-articular injection of Monovisc® in providing symptomatic relief of pain caused by idiopathic osteoarthritis (OA) of the knee as compared to a placebo comparator injection of sterile saline.

Official Title
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A Randomized, Double-Blind, Placebo Controlled, Multi-Center Study of a Single Injection Cross-Linked Sodium Hyaluronate to Provide Symptomatic Relief of Osteoarthritis of the Knee

Conditions
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Osteoarthritis

Intervention / Treatment
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* Device: Monovisc®
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Male or Female Age 35 to 75 years Body Mass Index (BMI) 20 to 40 kg/m2 Willing and able to provide informed consent Willing to limit analgesic use to acetaminophen 7 days prior to and 12 weeks after injection Not pregnant or lactating Previous conservative treatment regimen for osteoarthritis (OA) Diagnosis of idiopathic OA of the index knee OA symptoms for >= 6 months Index knee Kellgren-Lawrence (K-L) grade of II or III Index knee Baseline Summed WOMAC Pain Score >= 200mm and < 400mm after NSAID washout Contralateral Knee K-L grade 0, I or II Contralateral Knee Baseline WOMAC Pain Score < 150mm after NSAID washout Main Exclusion Criteria: Joint disorders which could interfere with treatment effectiveness Joint disorders which could interfere with study assessments Arthroscopy of either knee within 3 months of screening Open surgery of index knee within 12 months of screening Open surgery of contralateral knee within 3 months of screening Injection of Hyaluronic Acid (HA) in either knee within 6 months of screening Injection of steroid in index knee within 3 months of screening Any pre-treatment contraindication for injection or aspiration of the index knee, including cutaneous infection, intra-articular infection, knee deformity or condition which may jeopardize sterility or delivery of injection Synovial fluid aspirate volume > 20 milliliters (mL) Visual appearance of synovial fluid that contraindicates injection Index knee range of motion < 90 degrees Subject participation in other research study within 30 days of screening Subject unwilling to maintain active lifestyle, exercise program and body weight similar to that during 3 months prior to screening for duration of study Unwilling to maintain constant dosage of oral glucosamine or chondroitin sulfate for duration of study, if applicable Other medication or treatments that could interfere with study injection or assessments Allergy to gram positive bacterial products or intolerance of acetaminophen Active fibromyalgia Peripheral neuropathy severe enough to interfere with evaluation of either knee Vascular insufficiency severe enough to interfere with evaluation of the subject Hemiparesis involving either lower extremity Systemic bleeding disorder Other conditions which may adversely affect the success of the procedure

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 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: Monovisc®<br>Injectable Hyaluronic Acid Gel | Device: Monovisc®<br>* Intra-articular injection<br>* Other names: Hyaluronic Acid Gel;|
| Placebo Comparator: Saline<br>0.9% Sterile Saline | Other: Saline<br>* 0.9% Sterile Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score (ITT) >=40% and 15 mm From Baseline Through 12 Weeks | The primary endpoint measures the percentage of subjects (Monovisc vs. saline) who achieved >= a 40% improvement (reduction) in the WOMAC Pain Score and show at least 15 mm improvement (reduction) in the WOMAC Pain Score from baseline through 12 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score is a validated scale from 0 to 100 mm, where a higher score is equal to a higher pain level. The primary endpoint uses the ITT population that has data available for both baseline and 12 week time points. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluator Global Assessment Change From Baseline Through Week 12 (ITT) | Comparison of the change of the Evaluator Global Assessment from baseline through Week 12 between Monovisc and saline arms (ITT Population). The Evaluator Global Assessment is done by the Blinded Evaluator, and answers the question Considering all the ways the osteoarthritis in the patient's index knee affect him/her, what is your assessment of how much the patient's knee is bothering him/her today? The Evaluator Global Assessment is scored on a 0 to 100 mm Visual Analog Scale (VAS Scale), where a higher number means the patient is bothered to a higher degree. A negative number for the change from baseline indicates a reduction (improvement) in the assessment. The endpoint uses the ITT population that has data available for both baseline and 12 week time points. | 12 Weeks | 
| Patient Global Assessment Change From Baseline Through Week 12 (ITT) | Comparison of the change of the Patient Global Assessment from baseline through Week 12 between Monovisc and saline arms (ITT Population). The Patient Global Assessment is done by the patient, and answers the question Considering all the ways the osteoarthritis in your study knee affects you, what is your assessment of how much your study knee is bothering you today? The Patient Global Assessment is scored on a 0 to 100 mm Visual Analog Scale (VAS Scale), where a higher number means the patient is bothered to a higher degree. A negative number for the change from baseline indicates a reduction (improvement) in the assessment. The endpoint uses the ITT population that has data available for both baseline and 12 week time points. | 12 Weeks | 
| Range of Motion Change From Baseline Through Week 12 (ITT) | Comparison of the change of Range of Motion from baseline through Week 12 between Monovisc and saline arms (ITT Population). Range of motion is defined as the difference between flexion and extension in degrees where full extension range is 180 degrees. The endpoint uses the ITT population that has data available for both baseline and 12 week time points. | 12 Weeks | 
| WOMAC Physical Function Score Change From Baseline Through Week 12 (ITT) | This endpoint compares the change of the WOMAC Physical Function Score from baseline through Week 12 between Monovisc and saline arms (ITT Population). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Score is a validated scale from 0 to 100 mm, where a higher score is equal to a higher degree of functional limitation. A negative number for the change from baseline indicates improvement in physical function. The ITT population includes subjects with data at baseline and 12 Week time points. | 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Monovisc®, Hyaluronic Acid Gel, Injection, Knee