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

This study has been completed.
Sponsor:
Information provided by:
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00131352
First received: August 17, 2005
Last updated: December 15, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Osteoarthritis, Knee
Musculoskeletal Diseases
Device: hylan G-F 20
Other: Phosphate Buffered Saline
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • 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 [ Time Frame: Day 0, up to week 26 ] [ Designated as safety issue: No ]
    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:
  • 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 [ Time Frame: Day 0, Week 26 ] [ Designated as safety issue: No ]
    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 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 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 0, up to week 26 ] [ Designated as safety issue: No ]
    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 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 [ Time Frame: Day 0, Week 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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 Classified as Responders Per the Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Criteria at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]

    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


Enrollment: 253
Study Start Date: May 2005
Study Completion Date: September 2006
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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,
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00131352

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

No publications provided by Genzyme, a Sanofi Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT00131352     History of Changes
Other Study ID Numbers: SYNV00704
Study First Received: August 17, 2005
Results First Received: August 3, 2009
Last Updated: December 15, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Czech Republic: State Institute for Drug Control
Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: Ministry of Health, Welfare and Sport
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Genzyme, a Sanofi Company:
Osteoarthritis of the knee
Musculoskeletal

Additional relevant MeSH terms:
Musculoskeletal Diseases
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Rheumatic Diseases
Hyaluronic Acid
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Viscosupplements
Protective Agents

ClinicalTrials.gov processed this record on August 25, 2014