A Study of the Safety and Efficacy of Hylan G-F 20 (Synvisc) in Patients With Symptomatic Osteoarthritis of the Knee

Study Overview
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Brief Summary
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This clinical study is to evaluate the safety and efficacy of hylan G-F 20 (Synvisc) in patients with symptomatic knee osteoarthritis (OA). Patients will be given 6 mL of hylan G-F 20 (Synvisc) (or a phosphate buffered saline control), with a possible repeat treatment with Synvisc after the week 26 visit.

Detailed Description
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The trial included an initial 26 week treatment with 6 mL of hylan G-F 20 (Synvisc) (or a phosphate buffered saline control) followed by a 4 week repeat treatment of Synvisc.

Official Title
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A Multi-Centre, Parallel, Double-Blind, Blinded Evaluator, Randomised, Placebo-Controlled Evaluation of the Efficacy and Safety of a Single Dose of 6 mL of Synvisc in Patients With Symptomatic Osteoarthritis of the Knee

Conditions
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Osteoarthritis, Knee, Musculoskeletal Diseases

Intervention / Treatment
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* Device: hylan G-F 20
* Other: Phosphate Buffered Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with documented diagnosis of primary osteoarthritis (OA) of the target knee made at least 3 months prior to Screening, Has radiographic evidence of OA in the tibio-femoral compartment of the target, knee with at least 1 definite osteophyte and a measureable joint space, as diagnosed by standard X-rays taken not longer than 3 months prior to Screening, and before any baseline assessment, Has continued target knee pain despite conservative treatment (e.g. weight reduction, physical therapy, analgesics), Has pain in the target knee as demonstrated by a score of 2 or 3 on the Western Ontario and McMaster Universities Osteoarthritis Index Likert Scale Version 3.1 (WOMAC LK 3.1) A1 (Walking Pain) Subscale , Has a mean score of 1.5 to 3.5 on the Western Ontario and McMaster Universities Osteoarthritis Index Likert Scale Version 3.1 (WOMAC LK 3.1) A (Pain) Subscale. Inclusion Criteria for Repeat Phase: Must have no major safety concerns during the first course of treatment as assessed by the Investigator; Must have a WOMAC LK 3.1 A score of at least 1. Exclusion criteria: Has modified Kellgren-Lawrence Numerical Grading System of grade IV in the patello-femoral compartment of the target knee confirmed by standard X-rays taken not longer than 3 months prior to Screening, and before any baseline assessment, Has clinically apparent tense effusion of the target knee, Has had viscosupplementation in any joint including the target knee within 9 months prior to Screening, Has concomitant inflammatory disease or other condition that affects the joints (e.g. rheumatoid arthritis, metabolic bone disease, psoriasis, gout, symptomatic chondrocalcinosis and active infection, etc.,) Symptomatic OA of the contralateral knee or of either hip that is not responsive to paracetamol and requires other therapy, Has related hypersensitivities to avian proteins and/or any components of hyaluronan-based injection devices,

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synvisc<br>Participants with symptomatic primary osteoarthritis (OA) of the knee received a single injection of 6 mL hylan G-F 20 (Synvisc). | Device: hylan G-F 20<br>* Single injection of 6 mL of hylan G-F 20 (Synvisc).<br>* Other names: Synvisc-One;|
| Placebo Comparator: Saline Control<br>Participants (control group) with symptomatic primary osteoarthritis (OA) of the knee received a single injection of 6 mL phosphate buffered saline. | Other: Phosphate Buffered Saline<br>* Single injection of 6 mL phosphate buffered saline.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Knee Pain Over the Course of the 26-week Initial Treatment Period As Measured by Participants Using the Western Ontario and McMaster Universities Osteoarthritis Index Likert Scale Version 3.1 (WOMAC LK 3.1) A (Pain) Subscale | The change from baseline over the course of the 26-week initial treatment period using participants' assessment of pain. Mean scores were used for baseline (day 0) and for all visits up to week 26 (weeks 4, 8, 12, 18 and 26). The WOMAC Pain Subscale has a score range of 0-4, where 0=no pain and 4=extreme pain. | Day 0, up to week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Knee Pain at Week 26 As Measured by Participants Using the Western Ontario and McMaster Universities Osteoarthritis Index Likert Scale Version 3.1 (WOMAC LK 3.1) A (Pain) Subscale | The change from baseline to week 26 using participants' assessment of pain. The WOMAC Pain Subscale has a score range of 0-4, where 0=no pain and 4=extreme pain. | Day 0, Week 26 | 
| Participants Level of Pain While Walking at Week 26 As Measured by Participants Using the Western Ontario and McMaster Universities Osteoarthritis Index Likert Scale Version 3.1 (WOMAC LK 3.1) A1 (Walking Pain) Subscale | Participants categorized the pain they felt while walking using the WOMAC LK 3.1) A1 (Walking Pain) Subscale. The scale rates pain as none, mild, moderate, severe and extreme. | Week 26 | 
| Change From Baseline Over the Course of the 26-week Initial Treatment Period in Physical Function Measured by Participants Using the Western Ontario and McMaster Universities Osteoarthritis Index Likert Scale (WOMAC LK Version 3.1) C (Function) Subscale | The change from baseline over the course of the 26-week initial treatment period using participants' assessment of physical function. Mean scores were used for baseline (day 0) and for all visits up to week 26 (weeks 4, 8, 12, 18 and 26). The WOMAC Function Subscale has a score range of 0-4 to assess the degree of difficulty completing tasks within the past 48 hours, where 0=no difficulty and 4=extreme difficulty. | Day 0, up to week 26 | 
| Change From Baseline at Week 26 in Physical Function Measured by Participants Using the Western Ontario and McMaster Universities Osteoarthritis Index Likert Scale (WOMAC LK Version 3.1) C (Function) Subscale | The change from baseline to week 26 using participants' assessment of physical function. The WOMAC Function Subscale has a score range of 0-4 to assess the degree of difficulty completing tasks within the past 48 hours, where 0=no difficulty and 4=extreme difficulty. | Day 0, Week 26 | 
| Participant Global Assessment (PTGA) of the Target Knee Osteoarthritis Condition at Week 26 | The Participant Global Assessment (PTGA) was used by participants to rate their osteoarthritis (OA). PTGA uses 5 scoring levels: Very well=0, Well=1, Fair=2, Poor=3, Very poor=4. | Week 26 | 
| Clinical Observer Global Assessment (COGA) of the Target Knee Osteoarthritis (OA) Condition at Week 26 | The Blinded Clinical Observer gave a global assessment (COGA) of the target knee OA. COGA uses 5 scoring levels: Very well=0, Well=1, Fair=2, Poor=3, Very poor=4. | Week 26 | 
| Participants Classified as Responders Per the Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Criteria at Week 26 | Participants were classified as a positive responder if at least one of the following two conditions were met: A significant improvement in either the pain (WOMAC A) or physical function (WOMAC C) subscales, defined as both a ≥ 50% improvement from Baseline and an absolute change from Baseline of ≥ 20 normalised units (NU), OR Improvement in at least 2 of 3 subscales - pain (WOMAC A), physical function (WOMAC C) or Participant Global Assessment (PTGA). Improvement for all three scales is defined as ≥ 20% improvement from Baseline and an absolute change from Baseline of ≥ 10 NU | Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis of the knee, Musculoskeletal