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

• ClinicalTrials.gov Identifier: NCT01586338
• Recruitment Status: Completed
• First Posted: April 26, 2012
• Results First Posted: February 24, 2016
• Last Update Posted: February 24, 2016
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Osteoarthritis	Drug: Hylan G-F 20	Phase 4

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 237 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: March 2012
• Actual Primary Completion Date: September 2013
• Actual Study Completion Date: September 2013

Arms and Interventions

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 Name: Synvisc®

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Subscore (Walking Pain) at Week 26 [ Time Frame: Baseline, Week 26 (missing data imputed by Last Observation Carried Forward [LOCF]) ]
   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.
2. Overview of Adverse Events (AE) [ Time Frame: Up to Week 26 ]
   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.

Secondary Outcome Measures :

1. Change From Baseline in WOMAC A1 Subscore (Walking Pain) at Week 8 and 12 [ Time Frame: Baseline, Week 8 and Week 12 (missing data imputed by LOCF) ]
   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.
2. Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26 [ Time Frame: Baseline, Week 8, 12 and 26 (missing data imputed by LOCF) ]
   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.
3. Patient Global Assessment (PTGA) Score [ Time Frame: Baseline, Week 8, 12 and 26 (missing data imputed by LOCF) ]
   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.
4. Clinical Observer Global Assessment (COGA) Score [ Time Frame: Baseline, Week 8, 12 and 26 (missing data imputed by LOCF) ]
   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.
5. Percentage of Participants With Change in Concomitant Medication of Osteoarthritis Therapy at Week 26 [ Time Frame: Baseline up to 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.

Eligibility Criteria

• Ages Eligible for Study: 30 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

China

Sanofi-Aventis Administrative Office

Shangai, China

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT01586338
• Other Study ID Numbers: SYNVIL06244; U1111-1129-3321 ( Other Identifier: UTN ); EFC13912 ( Other Identifier: Sanofi )
• First Posted: April 26, 2012
• Results First Posted: February 24, 2016
• Last Update Posted: February 24, 2016
• Last Verified: January 2016

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Hylan; Viscosupplements; Protective Agents; Physiological Effects of Drugs