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

Osteoarthritis, Knee Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00131352
• Other study ID #: SYNV00704
• Status: Completed
• Phase: Phase 3
• First received: August 17, 2005
• Last updated: March 17, 2015
• Start date: May 2005
• Est. completion date: September 2006

Study information

• Verified date: March 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Czech Republic: State Institute for Drug ControlBelgium: Federal Agency for Medicinal Products and Health ProductsGermany: Federal Institute for Drugs and Medical DevicesNetherlands: Ministry of Health, Welfare and SportUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 253
• Est. completion date: September 2006
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Musculoskeletal Diseases
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Device:
• hylan G-F 20
Single injection of 6 mL of hylan G-F 20 (Synvisc).

Other:
• Phosphate Buffered Saline
Single injection of 6 mL phosphate buffered saline.

Locations

Country	Name	City	State
Belgium	Hopital Erasme	Bruxelles
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitair Ziekenhuis Gastuisberg Leuven	Leuven
Belgium	CHU Liege	Liege
Czech Republic	Faculty Hospital Bohunice	Brno
Czech Republic	Faculty Hospital Motol	Prague
Czech Republic	Institute of Rheumatology	Prague 2
Czech Republic	Faculty Thomayer Hospital	Prague 4
France	Hopital Henri Mondor	Creteil Cedex
France	CHU Dupuytren	Limoges Cedex
France	Hopital de la Conception	Marseille
France	Hopital Rangueil	Toulouse Cedex 9
France	CHU Hopital Trousseau	Tours Cedex
Germany	Johanna-Etienne Krankenhaus	Neuss
Netherlands	AMC/UVA	Amsterdam
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Kings College Hospital	London
United Kingdom	Trafford General Hospital	Manchester
United Kingdom	Freeman Hospital	Newcastle-upon-Tyne
United Kingdom	Nuffield Orthopaedic Centre	Oxford

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

Belgium,  Czech Republic,  France,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No