Study of Safety and Efficacy of 6 mL Synvisc-One (Hylan G-F 20) in Indian Patients With Symptomatic Osteoarthritis of Knee(s) After Initial and Repeat Treatment

Study Overview
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Brief Summary
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Primary Objective: To evaluate the safety and efficacy of a single 6 mL intraarticular (IA) injection of Synvisc-One in participants in India with symptomatic osteoarthritis (OA) of the knee(s). Secondary Objective: To evaluate the safety and short-term efficacy of a repeat treatment with Synvisc-One.

Detailed Description
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A period of approximately 19 months was anticipated from the time the first participants was enrolled in the study to the completion of the study (last participant out). Individual participant participation lasted from 7 to 13 months depending on the timing of repeat treatment.

Official Title
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A Multicenter, Prospective, Open-Label Study of the Safety and Efficacy of 6 mL Synvisc-One ® (Hylan G F 20) in Indian Patients With Symptomatic Osteoarthritis of the Knee(s) After Initial and Repeat Treatment

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: Synvisc-One


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participant aged 30 years or older, with active lifestyle. The participant must be able to read, understand, and sign an informed consent form, understand requirements for followup visits, and must be willing to provide information at the scheduled evaluations. The participant had a diagnosis of OA of the target knee confirmed by recent X-ray (mild to moderate joint space narrowing and/or osteophytes (ie, Kellgren Lawrence [KL] Grade I-III), predominant in the tibiofemoral compartment. WOMAC A1 baseline 100 mm visual analog scale (VAS) score from 40-80 mm (moderate or severe walking pain) in the target knee. Participants with bilateral disease may be 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 may also be treated with Synvisc-One and does not need to meet the KL grade knee specific inclusion criteria described above. The other criteria do apply. If female, must had a negative urine pregnancy test and continue to use a medically acceptable form of contraception for the duration of the study. Otherwise, females must had been surgically sterile or postmenopausal (as documented in the medical history) for at least 1 year. Exclusion Criteria: Significant (requiring surgical correction) valgus or varus deformity of the knee, ligamentous laxity, or meniscal instability. Concomitant inflammatory or any other disease/condition which may affect joints (eg, rheumatoid arthritis, metabolic bone disease, psoriasis, gout, pseudogout, or chondrocalcinosis). History of sepsis in any joint or any clinical concern for a subacute infectious process in the target joint. History of surgery in the target knee. Planned surgery on any lower extremity joint. Clinically significant venous or lymphatic stasis present in the leg(s). Clinically apparent tense effusion or inflammation at the target knee. Skin disease or infection in the area of the injection site. Any musculoskeletal condition that would impede measurement of efficacy at the target knee. Pregnant or lactating women. Hypersensitivities to avian proteins and/or any components of hyaluronan-based injection. Treatment with any hyaluronic acid (HA) or derivatives in the previous 6 months. Treatment with IA steroids in the previous 3 months. Any contraindication to IA injection, eg, anticoagulant therapy or clinical concern for potential coagulopathy (eg, liver disease). Any significant medical condition (eg, significant psychiatric or neurological disorders or active alcohol/drug abuse), any medical condition that is unstable/poorly controlled or other factors (eg, 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.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synvisc-One<br>Single 6 mL IA injection of Synvisc-One (48 mg of cross-linked hylan polymer) at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy (no major safety concerns and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 subscore [measurement of pain while walking on flat surface] between 40-80 mm, measured on a 0-100 mm scale with 0 represents no pain and 100 represents worst possible pain) at Week 26, 39 or 52 (Repeat treatment). | Drug: Synvisc-One<br>* intraarticular injection<br>* Other names: GZ402662; hylan G-F 20;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in WOMAC A1 Subscore at Week 26 | WOMAC is health status measure questionnaire comprising 3 subscales (pain, stiffness and physical function). WOMAC A1 (measure of pain during walking on a flat surface) was measured using a visual analogue scale (100 mm line marked by participants with total score ranging from 0-100). Lower score represents lower pain. | Baseline, Week 26 (missing data imputed by Last Observation Carried Forward [LOCF]). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in WOMAC A1 Subscore at Week 52 | WOMAC is health status measure questionnaire comprising 3 subscales (pain, stiffness and physical function). WOMAC A1 (measure of pain during walking on a flat surface) was measured using a visual analogue scale (100 mm line marked by participants with total score ranging from 0-100). Lower score represents lower pain. | Baseline, Week 52 (missing data imputed by LOCF) | 
| Change From Baseline in WOMAC A Score at Week 52 | WOMAC is health status measure questionnaire comprising 3 subscales (pain, stiffness and physical function). WOMAC A (measure of pain) calculated as a mean of 5 individual components, measured using a visual analogue scale (100 mm line marked by participants with score ranging from 0-100). Total score range is 0 to 100, where higher scores indicate higher pain. | Baseline, Week 52 (missing data imputed by LOCF) | 
| Change From Baseline in WOMAC B Score at Week 52 | WOMAC is health status measure questionnaire comprising 3 subscales (pain, stiffness and physical function). WOMAC B (measure of stiffness) calculated as a mean of 2 individual components, measured using a visual analogue scale (100 mm line marked by participants with score ranging from 0-100). Total score range is 0 to 100, where higher scores indicate higher stiffness. Stiffness is defined as a sensation of decreased ease in movement of joint. | Baseline, Week 52 (missing data imputed by LOCF) | 
| Change From Baseline in WOMAC C Score at Week 52 | WOMAC is health status measure questionnaire comprising 3 subscales (pain, stiffness and physical function). WOMAC C (measure of physical function) calculated as a mean of 17 individual components, measured using a visual analogue scale (100 mm line marked by participants with score ranging from 0-100). Total score range is 0 to 100, where higher scores indicate higher worse function. Physical function refers to participant's ability to move around and perform usual activities of daily living. | Baseline, Week 52 (missing data imputed by LOCF) | 
| Patient Global Assessment (PTGA) Score at Week 52 | PTGA (global 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. Number of participants with different categories of PTGA score at Week 52 are reported. | Week 52 (missing data imputed by LOCF) | 
| Clinician Observer Global Assessment (COGA) Score at Week 52 | COGA (global 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 the physician to rate participant's osteoarthritis condition. Number of participants with different categories of PTGA score at Week 52 are reported. | Week 52 (missing data imputed by LOCF). | 
| 12-Item Short Form Health Survey (SF-12) | SF-12 health survey is a self-reported questionnaire to measure participant's profile of functional health and well-being. It includes following 12 questions (Q): Q1 In general, health status; Q2a Limitation of moderate activities; Q2b Limitation of climbing; Q3a Less accomplishment due to physical health; Q3b Limited in the kind of work or other activities due to physical health; Q4a Less accomplishment due to emotional problems; Q4b Did work or other activities less carefully than usual due to emotional problems; Q5 Pain interfere with normal work; Q6a Felt calm and peaceful; Q6b Had lot of energy; Q6c Felt downhearted and low; and Q7 Physical health or emotional problems interfered with social activities. Number of participants with response to each Q are reported. | Baseline, Week 26, 52 | 
| Number of Participants With Change in Concomitant Medication of Osteoarthritis Therapy at Week 52 | 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 0) state. Any change in the therapy (increased therapy, decrease therapy, no change in therapy) during the study was reported. | Baseline up to Week 52 | 
| Time Between Initial and Repeat Synvisc-One Treatment | Time Between initial and repeat Synvisc-One Treatment was duration between initial and repeat injection in those participants who received repeat injection. | Baseline up to Week 52 | 
| Change From Baseline in WOMAC A1 Subscore After Repeat Injection | WOMAC is health status measure questionnaire comprising 3 subscales (pain, stiffness and physical function). WOMAC A1 (measure of pain during walking on a flat surface) was measured using a visual analogue scale (100 mm line marked by participants with total score ranging from 0-100). Lower score represents lower pain. Data are reported for those participants who received repeat injection. Here, baseline represents the day at which a participant received repeat injection (Week 26, 39 or 52). | Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF) | 
| Change From Baseline in WOMAC A Score After Repeat Injection | WOMAC is health status measure questionnaire comprising 3 subscales (pain, stiffness and physical function). WOMAC A (measure of pain) calculated as a mean of 5 individual components, measured using a visual analogue scale (100 mm line marked by participants with score ranging from 0-100). Total score range is 0 to 100, where higher scores indicate higher pain. Data are reported for those participants who received repeat injection. Here, baseline represents the day at which a participant received repeat injection (Week 26, 39 or 52). | Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF) | 
| Change From Baseline in WOMAC B Score After Repeat Injection | WOMAC is health status measure questionnaire comprising 3 subscales (pain, stiffness and physical function). WOMAC B (measure of stiffness) calculated as a mean of 2 individual components, measured using a visual analogue scale (100 mm line marked by participants with score ranging from 0-100). Total score range is 0 to 100, where higher scores indicate higher stiffness. Stiffness is defined as a sensation of decreased ease in movement of joint. Data are reported for those participants who received repeat injection. Here, baseline represents the day at which a participant received repeat injection (Week 26, 39 or 52). | Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF) | 
| Change From Baseline in WOMAC C Score After Repeat Injection | WOMAC is health status measure questionnaire comprising 3 subscales (pain, stiffness and physical function). WOMAC C (measure of physical function) calculated as a mean of 17 individual components, measured using a visual analogue scale (100 mm line marked by participants with score ranging from 0-100). Total score range is 0 to 100, where higher scores indicate higher worse function. Physical function refers to participant's ability to move around and perform usual activities of daily living. Data are reported for those participants who received repeat injection. Here, baseline represents the day at which a participant received repeat injection (Week 26, 39 or 52). | Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF) |