A Study of the Efficacy and Safety of Synvisc® in Chinese Subjects With Symptomatic Osteoarthritis of the Knee(s)

A Multicenter, Prospective, Open-label, Single Arm Study of the Efficacy and Safety of Synvisc® (Hylan G-F 20) in Chinese Subjects With Symptomatic Osteoarthritis of the Knee(s)

Primary Objective:

• To evaluate the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 subscore (walking pain) at 26 weeks compared to the Baseline score
• To evaluate the safety using the incidence, severity, seriousness, relatedness, and frequency of all treatment emergent Adverse Events (AEs)

Secondary Objectives:

• To evaluate the change in WOMAC A1 subscore (walking pain) between baseline and weeks 8, and 12
• To evaluate the change in WOMAC A, B and C score between baseline and weeks 8, 12 and 26
• To evaluate the change in Patient Global Assessment (PTGA) score between baseline and weeks 8, 12 and 26
• To evaluate the change in Clinical Observer Global Assessment (COGA) score between baseline and weeks 8, 12 and 26
• To evaluate the change in concomitant Osteoarthritis (OA) therapy over 26 weeks and between baseline and weeks 1, 2, 8, 12 and 26

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: Hylan G-F 20

Detailed Description

Duration of study period for each participants was 26-28 weeks.

• Study Type: Interventional
• Enrollment (Actual): 237
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shangai, China
    • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

1. The participants had a diagnosis of OA of the Target Knee confirmed by recent X-Ray (mild to moderate joint space narrowing and/or osteophytes predominant in the tibiofemoral compartment)
2. WOMAC A1 baseline 100 mm Visual Analog Score (VAS) between 40-80 mm (moderate or severe walking pain) in the Target knee

3. Participants with bilateral disease included in the study with the below strict conditions:

   • Only one knee included in the efficacy assessment and considered the Target Knee (The worst knee by the WOMAC A1 pain scale should be selected). The selected knee must meet the inclusion and exclusion criteria
   • The non-target knee might also be treated with Synvisc® and did not need to meet the Kellgren-Lawrence (KL) grade knee specific inclusion criteria described above. The other criteria applied, and included in safety assessment
4. Pre-menopausal female participants had a negative urine pregnancy test and continue to use a medically acceptable form of contraception for the duration of the study. Otherwise, females had been surgically sterile, or postmenopausal (as documented in medical history) for at least 1 year

Exclusion criteria:

1. Significant (requiring surgical correction) valgus or varus deformity of the knee, ligamentous laxity, or meniscal instability
2. Concomitant inflammatory or any other disease/condition which might affect joints (e.g., rheumatoid arthritis, metabolic bone disease, psoriasis, gout, pseudogout, chondrocalcinosis etc)
3. History of sepsis in any joint or any clinical concern for a sub-acute infectious process in the target joint
4. History of surgery in the target knee (if done < 6 months)
5. Planned surgery on any lower extremity joint
6. Presence of clinically significant venous or lymphatic stasis in the leg(s)
7. Clinically apparent tense effusion or inflammation at the target knee
8. Skin disease or infection in the area of the injection site
9. Any musculoskeletal condition that would impede measurement of efficacy at the target knee
10. Pregnant or lactating women
11. Hypersensitivities to avian proteins and/or any components of hyaluronan-based injection
12. Treatment with any Hyaluronic Acid (HA) or derivatives in the previous 6 months.
13. Treatment with Intra-Articular (IA) steroid in the previous 3 months
14. Any contra-indication to IA injection e.g., anticoagulant therapy or clinical concern for potential coagulopathy (e.g. liver disease)
15. Any significant medical condition (e.g., significant psychiatric or neurological disorders, active alcohol/drug abuse, etc), any medical condition that is unstable/poorly controlled or other factor (e.g., planned relocation) that the Investigator felt would interfere with study evaluations and study participation

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Synvisc; Three intra-articular (IA) injections of Synvisc (2.25 ml glass syringe containing 16 mg hylan G-F 20) at intervals of one week. The total duration of observation was 26 weeks.	Drug: Hylan G-F 20; Intra-articular injection (pre-filled glass syringe); Other Names: Synvisc®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Subscore (Walking Pain) at Week 26	WOMAC is health status measure questionnaire of twenty-four questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A1 (walking pain) was measured on a scale of 0-100 mm, where lower score represents lower pain and higher score represents higher pain.	Baseline, Week 26 (missing data imputed by Last Observation Carried Forward [LOCF])
Overview of Adverse Events (AE)	An AE could be any unfavorable and unintended symptom, sign, disease or condition, or test abnormality whether or not considered related to the investigational product. A serious adverse event (SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAE): AEs that developed/worsened during the 'on treatment period' (from first dose of study drug until the end of study period). Category "AE" included participant with both serious and non-serious AE.	Up to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in WOMAC A1 Subscore (Walking Pain) at Week 8 and 12	WOMAC is health status measure questionnaire of twenty-four questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A1 (walking pain) was measured on a scale of 0-100 mm, where lower score represents lower pain and higher score represents higher pain.	Baseline, Week 8 and Week 12 (missing data imputed by LOCF)
Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26	WOMAC is health status measure questionnaire of twenty-four questions comprising 3 subscales (pain, stiffness and physical function). Each question was measured on a scale of 0-100 mm where lower score represents lower pain (better condition) and higher score represents higher pain. WOMAC A (measure of pain during walking on a flat surface) was sum of first five items with total score ranging from 0-500 mm, Lower score represents lower pain and higher score represents higher pain. WOMAC B (Stiffness) is the sum of the sixth and seventh item, it is in the range of 0-200 mm. WOMAC C (function) is the sum of the eighth to twenty-forth item, the score is in the range of 0-1700 mm.	Baseline, Week 8, 12 and 26 (missing data imputed by LOCF)
Patient Global Assessment (PTGA) Score	PTGA (self-assessment of target knee osteoarthritis condition) was measured using the 5 point Likert scale (0=very well, 1=well, 2=fair, 3=poor, 4=very poor) by participants to rate the osteoarthritis condition. Percentage of participants with different categories of PTGA score at baseline, Week 8, 12 and 26 are reported.	Baseline, Week 8, 12 and 26 (missing data imputed by LOCF)
Clinical Observer Global Assessment (COGA) Score	COGA (assessment of target knee osteoarthritis condition) was measured using the 5 point Likert scale (0=very well, 1=well, 2=fair, 3=poor, 4=very poor) by the physician to rate participant's osteoarthritis condition. Percentage of participants with different categories of COGA score at baseline,Week 8, 12 and 26 are reported.	Baseline, Week 8, 12 and 26 (missing data imputed by LOCF)
Percentage of Participants With Change in Concomitant Medication of Osteoarthritis Therapy at Week 26	Participants were asked about their perception regarding any additional Osteoarthritis medications or treatments or any changes in regimen or dosages compared to their baseline (Day 1) state. Any change in the therapy (less use of other therapies, more use of other therapies and no change in use of other therapies) during the study was reported.	Baseline up to Week 26

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): September 1, 2013

Study Registration Dates

• First Submitted: April 23, 2012
• First Submitted That Met QC Criteria: April 24, 2012
• First Posted (ESTIMATE): April 26, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): February 24, 2016
• Last Update Submitted That Met QC Criteria: January 27, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Protective Agents; Viscosupplements; Hylan
• Other Study ID Numbers: SYNVIL06244; U1111-1129-3321 (OTHER: UTN); EFC13912 (OTHER: Sanofi)