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

Phase 3

Completed

Conditions: Osteoarthritis, Knee
Musculoskeletal Diseases

Interventions: Other: Phosphate Buffered Saline
Device: hylan G-F 20

Registration Number: NCT00131352

Lead Sponsor: Genzyme, a Sanofi Company

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 253

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,

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saline Control	Phosphate Buffered Saline	Participants (control group) with symptomatic primary osteoarthritis (OA) of the knee received a single injection of 6 mL phosphate buffered saline.
Synvisc	hylan G-F 20	Participants with symptomatic primary osteoarthritis (OA) of the knee received a single injection of 6 mL hylan G-F 20 (Synvisc).

Primary Outcome Measures

Name	Time	Method
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	Day 0, up to week 26	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.

Secondary Outcome Measures

Name	Time	Method
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	Day 0, Week 26	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.
Participant Global Assessment (PTGA) of the Target Knee Osteoarthritis Condition at Week 26	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.
Clinical Observer Global Assessment (COGA) of the Target Knee Osteoarthritis (OA) Condition at Week 26	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.
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	Week 26	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.
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	Day 0, up to week 26	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.
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	Day 0, Week 26	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.
Participants Classified as Responders Per the Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Criteria at Week 26	Week 26	Participants were classified as a positive responder if at least one of the following two conditions were met: 1. 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 2. 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

Trial Locations

Locations (21): Hopital Henri Mondor
🇫🇷
Creteil Cedex, France
Faculty Hospital Motol
🇨🇿
Prague, Czech Republic
CHU Dupuytren
🇫🇷
Limoges Cedex, France
Hopital de la Conception
🇫🇷
Marseille, France
Johanna-Etienne Krankenhaus
🇩🇪
Neuss, Germany
Hopital Rangueil
🇫🇷
Toulouse Cedex 9, France
Trafford General Hospital
🇬🇧
Manchester, United Kingdom
Kings College Hospital
🇬🇧
London, United Kingdom
Nuffield Orthopaedic Centre
🇬🇧
Oxford, United Kingdom
Freeman Hospital
🇬🇧
Newcastle-upon-Tyne, United Kingdom
Hopital Erasme
🇧🇪
Bruxelles, Belgium
Faculty Hospital Bohunice
🇨🇿
Brno, Czech Republic
AMC/UVA
🇳🇱
Amsterdam, Netherlands
CHU Hopital Trousseau
🇫🇷
Tours Cedex, France
University Hospital of Wales
🇬🇧
Cardiff, United Kingdom
Universitair Ziekenhuis Gent
🇧🇪
Gent, Belgium
CHU Liege
🇧🇪
Liege, Belgium
Institute of Rheumatology
🇨🇿
Prague 2, Czech Republic
Academisch Ziekenhuis Maastricht
🇳🇱
Maastricht, Netherlands
Universitair Ziekenhuis Gastuisberg Leuven
🇧🇪
Leuven, Belgium
Faculty Thomayer Hospital
🇨🇿
Prague 4, Czech Republic