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

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

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.

Study Overview

• Status: Completed
• Conditions: Musculoskeletal Diseases; Osteoarthritis, Knee
• Intervention / Treatment: Device: hylan G-F 20; Other: Phosphate Buffered Saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 253
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • Hopital Erasme
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Gastuisberg Leuven
  • Liege, Belgium, 4000
    • CHU Liège
• Czech Republic
  • Brno, Czech Republic, 62500
    • Faculty Hospital Bohunice
  • Prague, Czech Republic, 15006
    • Faculty Hospital Motol
  • Prague 2, Czech Republic, 12850
    • Institute of Rheumatology
  • Prague 4, Czech Republic, 14059
    • Faculty Thomayer Hospital
• France
  • Creteil Cedex, France, 94010
    • Hôpital Henri Mondor
  • Limoges Cedex, France, 87042
    • CHU Dupuytren
  • Marseille, France, 13005
    • Hopital de la Conception
  • Toulouse Cedex 9, France, 31059
    • Hopital Rangueil
  • Tours Cedex, France, 37044
    • CHU Hôpital Trousseau
• Germany
  • Neuss, Germany, 41462
    • Johanna-Etienne Krankenhaus
• Netherlands
  • Amsterdam, Netherlands, 1100
    • AMC/UVA
  • Maastricht, Netherlands, 6202 AZ
    • Academisch Ziekenhuis Maastricht
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • London, United Kingdom, SE5 9RJ
    • Kings College Hospital
  • Manchester, United Kingdom, M41 5SL
    • Trafford General Hospital
  • Newcastle-upon-Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
  • Oxford, United Kingdom, OX3 7LD
    • Nuffield Orthopaedic Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Synvisc; 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; Single injection of 6 mL of hylan G-F 20 (Synvisc).; Other Names: Synvisc-One
Placebo Comparator: Saline Control; 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; Single injection of 6 mL phosphate buffered saline.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Publications and helpful links

General Publications

• Chevalier X, Jerosch J, Goupille P, van Dijk N, Luyten FP, Scott DL, Bailleul F, Pavelka K. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial. Ann Rheum Dis. 2010 Jan;69(1):113-9. doi: 10.1136/ard.2008.094623.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): September 1, 2006
• Study Completion (Actual): September 1, 2006

Study Registration Dates

• First Submitted: August 17, 2005
• First Submitted That Met QC Criteria: August 17, 2005
• First Posted (Estimate): August 18, 2005

Study Record Updates

• Last Update Posted (Estimate): April 3, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Musculoskeletal; Osteoarthritis of the knee
• Additional Relevant MeSH Terms: Joint Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Musculoskeletal Diseases; Physiological Effects of Drugs; Protective Agents; Viscosupplements; Hylan
• Other Study ID Numbers: SYNV00704