Euflexxa for the Treatment of Osteoarthritis

Study Overview
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Brief Summary
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The effect of Euflexxa therapy for knee osteoarthritis on levels of inflammatory and degenerative synovial fluid bio-markers in patients with knee osteoarthritis

Detailed Description
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The FLEXX trial was the first well-controlled, randomized, double-blind, multicenter study evaluating the efficacy of Euflexxa (1% sodium hyaluronate) therapy for knee osteoarthritis. Five-hundred-and-eighty patients were randomized to receive either Euflexxa or normal saline. There were significant improvements in the Visual analogue scale score Osteoarthritis Research Society International responder index, HRQoL, and function at 26-week follow-up.1 However, the FLEXX trial did not evaluate changes in synovial fluid bio-marker levels. The present study will be a prospective pilot study of 25 subjects who will receive intra-articular Euflexxa. The primary objective of this study is to prospectively determine, at 6-weeks, and 6-months post treatment, the changes in levels of synovial fluid biomarkers from pre- to post-injection in patients who receive Euflexxa. In addition, we will assess patient reported pain and patient reported outcomes up to 2 years from initiation of study.

Official Title
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A Prospective Pilot Study to Evaluate Efficacy and Safety of Euflexxa for the Treatment of Osteoarthritis

Conditions
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Osteo Arthritis Knee

Intervention / Treatment
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* Device: Euflexxa


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: OA of the knee by American College of Rheumatology criteria Those who failed non-pharmacological measures or simple analgesics moderate to severe pain score of 41 to 90 mm recorded on 100-mm visual analog scale (VAS) immediately following a 50-foot walk bilateral standing anterior-posterior radiograph demonstrating Kellgren and Lawrence grade 2 or 3 OA of the target knee ability and willingness to use only acetaminophen as the analgesic (rescue) study medication unassisted walking 50 feet on a flat surface and going up and down stairs willingness and ability to complete efficacy and safety questionnaires Exclusion criteria: Age less than 18 years any major injury to the target knee within the prior 12 months any surgery to the target knee within the prior 12 months surgery to the contralateral knee or other weight-bearing inflammatory arthropathies gout or pseudogout within the previous 6 months radiographic acute fracture, severe loss of bone density, avascular necrosis, and/or severe bone or joint deformity in the target knee osteonecrosis of either knee fibromyalgia, pes anserine bursitis, lumbar radiculopathy, and/or neurogenic or vascular claudication target knee joint infection or skin disorder/ infection within the previous 6 months symptomatic OA of the hips, spine, or ankle; known hypersensitivity to acetaminophen, IA-BioHA, or phosphate-buffered saline solution Women of childbearing potential who are pregnant, nursing, or planning to become pregnant, and those who do not agree to remain on an acceptable method of birth control throughout the study history of immune disorders; vascular insufficiency of lower limbs or peripheral neuropathy current treatment or treatment of cancer within the previous 2 years (excluding basal cell or squamous cell carcinoma of the skin) active liver or renal disease any clinically significant abnormal laboratory value [to be defined in detail at a later point] any intercurrent chronic disease or condition that might interfere with the completion of the study participation in any experimental device study within the prior 6 months or any experimental drug study within the prior month

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Euflexxa<br>Two sets of Euflexxa injection at 0 and 6 months. Each set consists of 3 injections 1 week apart. | Device: Euflexxa<br>* Aspirations performed before each injection and at six weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in hyaluronate | The concentration of hyaluronate in the synovial fluid will be measured using Fluorophore-assisted carbohydrate electrophoresis. The mean concentration at baseline, and the change in mean concentration with the injection will be studied. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Tissue Necrosis Factor-alpha (TNF-α) | The levels of TNF-α in the synovial fluid will be measured using Enzyme-linked immunosorbent assay. The mean concentration at baseline, and the change in mean concentration with the injection will be studied. | 6 months | 
| Changes in Tumor necrosis factor-stimulated gene 6 (TSG-6) | The levels of TSG-6 in the synovial fluid will be measured using Enzyme-linked immunosorbent assay. The mean concentration at baseline, and the change in mean concentration with the injection will be studied. | 6 months | 
| VAS pain score | Change in VAS (visual analogue scale) pain score compared to baseline in the study cohort. VAS is a measure of pain with 10 being worst pain on a 10cm scale (100 mm). | 2 years | 
| Veterans Rand-12 (VR-12) physical composite score (PCS) | Change in VR-12 PCS compared to baseline in the study cohort PCS range from 0 to 100, where a zero score indicates the lowest level of health and 100 indicates the highest level of health. | 2 years | 
| Veterans Rand-12 (VR-12) mental composite score (MCS) | Change in VR-12 MCS compared to baseline in the study cohort. MCS range from 0 to 100, where a zero score indicates the lowest level of health and 100 indicates the highest level of health. | 2 years | 
| UCLA activity score | Change in UCLA activity score compared to baseline in the study cohort. UCLA activity scores range from 1 to 10, and is a measure of activity with 10 being most active. | 2 years |