OASIS: 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

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02389452
• Collaborator: (none)
• Enrollment: 394
• Arm: 1
• Duration (Months): 19

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis	Drug: Synvisc-One	Phase 4

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 394 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Synvisc-One 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; intraarticular injection; Other Names: GZ402662; hylan G-F 20

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in WOMAC A1 Subscore at Week 26 [Baseline, Week 26 (missing data imputed by Last Observation Carried Forward [LOCF]).]

   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.

Secondary Outcome Measures

1. Change From Baseline in WOMAC A1 Subscore at Week 52 [Baseline, Week 52 (missing data imputed by LOCF)]

   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.

2. Change From Baseline in WOMAC A Score at Week 52 [Baseline, Week 52 (missing data imputed by LOCF)]

   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.

3. Change From Baseline in WOMAC B Score at Week 52 [Baseline, Week 52 (missing data imputed by LOCF)]

   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.

4. Change From Baseline in WOMAC C Score at Week 52 [Baseline, Week 52 (missing data imputed by LOCF)]

   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.

5. Patient Global Assessment (PTGA) Score at Week 52 [Week 52 (missing data imputed by LOCF)]

   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.

6. Clinician Observer Global Assessment (COGA) Score at Week 52 [Week 52 (missing data imputed by LOCF).]

   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.

7. 12-Item Short Form Health Survey (SF-12) [Baseline, Week 26, 52]

   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.

8. Number of Participants With Change in Concomitant Medication of Osteoarthritis Therapy at Week 52 [Baseline up to 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.

9. Time Between Initial and Repeat Synvisc-One Treatment [Baseline up to Week 52]

   Time Between initial and repeat Synvisc-One Treatment was duration between initial and repeat injection in those participants who received repeat injection.

10. Change From Baseline in WOMAC A1 Subscore After Repeat Injection [Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF)]

    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).

11. Change From Baseline in WOMAC A Score After Repeat Injection [Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF)]

    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).

12. Change From Baseline in WOMAC B Score After Repeat Injection [Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF)]

    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).

13. Change From Baseline in WOMAC C Score After Repeat Injection [Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF)]

    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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02389452
• Other Study ID Numbers: SYNV03809; U1111-1167-6813
• First Posted: Mar 17, 2015
• Last Update Posted: Aug 7, 2017
• Last Verified: Aug 1, 2017

• Additional relevant MeSH terms: Osteoarthritis; Hylan

Study Results

Participant Flow

Recruitment Details	The study was conducted at 36 sites in India between February 16, 2010 and September 7, 2011.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL intra-articular (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 at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52 ) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Period Title: Overall Study
STARTED	394
Participants Received Repeat Injection	11
COMPLETED	369
NOT COMPLETED	25

Baseline Characteristics

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Overall Participants	394
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.6 (9.80)
Sex: Female, Male (Count of Participants)
Female	285 72.3%
Male	109 27.7%
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	70.72 (11.526)
Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	160.11 (8.836)
Body Mass Index (kilogram per square meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter]	27.66 (4.477)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in WOMAC A1 Subscore at Week 26
Description	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.
Time Frame	Baseline, Week 26 (missing data imputed by Last Observation Carried Forward [LOCF]).

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	394
Mean (Standard Deviation) [units on a scale]	-28.0 (19.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Synvisc-One
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t-test
	Comments

2. Secondary Outcome

Title	Change From Baseline in WOMAC A1 Subscore at Week 52
Description	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.
Time Frame	Baseline, Week 52 (missing data imputed by LOCF)

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed=participants with baseline and Week 52 data.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	388
Mean (Standard Deviation) [units on a scale]	-32.7 (19.95)

3. Secondary Outcome

Title	Change From Baseline in WOMAC A Score at Week 52
Description	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.
Time Frame	Baseline, Week 52 (missing data imputed by LOCF)

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed=participants with baseline and Week 52 data.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	388
Mean (Standard Deviation) [units on a scale]	-29.18 (19.158)

4. Secondary Outcome

Title	Change From Baseline in WOMAC B Score at Week 52
Description	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.
Time Frame	Baseline, Week 52 (missing data imputed by LOCF)

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed=participants with baseline and Week 52 data.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	388
Mean (Standard Deviation) [units on a scale]	-25.77 (22.047)

5. Secondary Outcome

Title	Change From Baseline in WOMAC C Score at Week 52
Description	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.
Time Frame	Baseline, Week 52 (missing data imputed by LOCF)

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed=participants with baseline and Week 52 data.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	388
Mean (Standard Deviation) [units on a scale]	-25.72 (19.449)

6. Secondary Outcome

Title	Patient Global Assessment (PTGA) Score at Week 52
Description	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.
Time Frame	Week 52 (missing data imputed by LOCF)

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed=participants with baseline and Week 52 data.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	388
Very well	82 20.8%
Well	175 44.4%
Fair	90 22.8%
Poor	40 10.2%
Very poor	1 0.3%

7. Secondary Outcome

Title	Clinician Observer Global Assessment (COGA) Score at Week 52
Description	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.
Time Frame	Week 52 (missing data imputed by LOCF).

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analyzed=participants with baseline and Week 52 data.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	388
Very well	77 19.5%
Well	177 44.9%
Fair	98 24.9%
Poor	35 8.9%
Very poor	1 0.3%

8. Secondary Outcome

Title	12-Item Short Form Health Survey (SF-12)
Description	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.
Time Frame	Baseline, Week 26, 52

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants evaluable for baseline, Week 26 and Week 52 were 394, 394 and 388, respectively.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	394
Q1: Excellent/Very Good, Baseline	35 8.9%
Q1: Excellent/Very Good, Week 26	87 22.1%
Q1: Excellent/Very Good, Week 52	135 34.3%
Q1: Good, Baseline	139 35.3%
Q1: Good, Week 26	230 58.4%
Q1: Good, Week 52	189 48%
Q1: Fair/Poor, Baseline	219 55.6%
Q1: Fair/Poor, Week 26	76 19.3%
Q1: Fair/Poor, Week 52	64 16.2%
Q1: Missing, Baseline	1 0.3%
Q1: Missing, Week 26	1 0.3%
Q1: Missing, Week 52	0 0%
Q2a: Yes, Limited a Lot/a Little, Baseline	367 93.1%
Q2a: Yes, Limited a Lot/a Little, Week 26	303 76.9%
Q2a: Yes, Limited a Lot/a Little, Week 52	293 74.4%
Q2a: No Not Limited at All, Baseline	24 6.1%
Q2a: No Not Limited at All, Week 26	90 22.8%
Q2a: No Not Limited at All, Week 52	95 24.1%
Q2a: Missing, Baseline	3 0.8%
Q2a: Missing, Week 26	1 0.3%
Q2a: Missing, Week 52	0 0%
Q2b: Yes, Limited a Lot/a Little, Baseline	373 94.7%
Q2b: Yes, Limited a Lot/a Little, Week 26	338 85.8%
Q2b: Yes, Limited a Lot/a Little, Week 52	334 84.8%
Q2b: No Not Limited at All, Baseline	19 4.8%
Q2b: No Not Limited at All, Week 26	55 14%
Q2b: No Not Limited at All, Week 52	54 13.7%
Q2b: Missing, Baseline	2 0.5%
Q2b: Missing, Week 26	1 0.3%
Q2b: Missing, Week 52	0 0%
Q3a: All/Most of the Time, Baseline	152 38.6%
Q3a: All/Most of the Time, Week 26	62 15.7%
Q3a: All/Most of the Time, Week 52	76 19.3%
Q3a: Some of the Time, Baseline	163 41.4%
Q3a: Some of the Time, Week 26	170 43.1%
Q3a: Some of the Time, Week 52	142 36%
Q3a: A Little/None of the Time, Baseline	76 19.3%
Q3a: A Little/None of the Time, Week 26	159 40.4%
Q3a: A Little/None of the Time, Week 52	169 42.9%
Q3a: Missing, Baseline	3 0.8%
Q3a: Missing, Week 26	3 0.8%
Q3a: Missing, Week 52	1 0.3%
Q3b: All/Most of the Time, Baseline	137 34.8%
Q3b: All/Most of the Time, Week 26	58 14.7%
Q3b: All/Most of the Time, Week 52	57 14.5%
Q3b: Some of the Time, Baseline	158 40.1%
Q3b: Some of the Time, Week 26	147 37.3%
Q3b: Some of the Time, Week 52	148 37.6%
Q3b: A Little/None of the Time, Baseline	96 24.4%
Q3b: A Little/None of the Time, Week 26	187 47.5%
Q3b: A Little/None of the Time, Week 52	183 46.4%
Q3b: Missing, Baseline	3 0.8%
Q3b: Missing, Week 26	2 0.5%
Q3b: Missing, Week 52	0 0%
Q4a: All/Most of the Time, Baseline	114 28.9%
Q4a: All/Most of the Time, Week 26	60 15.2%
Q4a: All/Most of the Time, Week 52	58 14.7%
Q4a: Some of the Time, Baseline	149 37.8%
Q4a: Some of the Time, Week 26	115 29.2%
Q4a: Some of the Time, Week 52	132 33.5%
Q4a: A Little/None of the Time, Baseline	128 32.5%
Q4a: A Little/None of the Time, Week 26	217 55.1%
Q4a: A Little/None of the Time, Week 52	198 50.3%
Q4a: Missing, Baseline	3 0.8%
Q4a: Missing, Week 26	2 0.5%
Q4a: Missing, Week 52	0 0%
Q4b: All/Most of the Time, Baseline	88 22.3%
Q4b: All/Most of the Time, Week 26	48 12.2%
Q4b: All/Most of the Time, Week 52	56 14.2%
Q4b: Some of the Time, Baseline	166 42.1%
Q4b: Some of the Time, Week 26	131 33.2%
Q4b: Some of the Time, Week 52	128 32.5%
Q4b: A Little/None of the Time, Baseline	137 34.8%
Q4b: A Little/None of the Time, Week 26	213 54.1%
Q4b: A Little/None of the Time, Week 52	204 51.8%
Q4b: Missing, Baseline	3 0.8%
Q4b: Missing, Week 26	2 0.5%
Q4b: Missing, Week 52	0 0%
Q5: Not at All/A Little Bit, Baseline	70 17.8%
Q5: Not at All/A Little Bit, Week 26	207 52.5%
Q5: Not at All/A Little Bit, Week 52	219 55.6%
Q5: Moderately, Baseline	182 46.2%
Q5: Moderately, Week 26	122 31%
Q5: Moderately, Week 52	105 26.6%
Q5: Quite a Bit/Extremely, Baseline	140 35.5%
Q5: Quite a Bit/Extremely, Week 26	63 16%
Q5: Quite a Bit/Extremely, Week 52	64 16.2%
Q5: Missing, Baseline	2 0.5%
Q5: Missing, Week 26	2 0.5%
Q5: Missing, Week 52	0 0%
Q6a: All/Most of the Time, Baseline	188 47.7%
Q6a: All/Most of the Time, Week 26	240 60.9%
Q6a: All/Most of the Time, Week 52	244 61.9%
Q6a: Some of the Time, Baseline	112 28.4%
Q6a: Some of the Time, Week 26	106 26.9%
Q6a: Some of the Time, Week 52	121 30.7%
Q6a: A Little/None of the Time, Baseline	92 23.4%
Q6a: A Little/None of the Time, Week 26	46 11.7%
Q6a: A Little/None of the Time, Week 52	23 5.8%
Q6a: Missing, Baseline	2 0.5%
Q6a: Missing, Week 26	2 0.5%
Q6a: Missing, Week 52	0 0%
Q6b: All/Most of the Time, Baseline	122 31%
Q6b: All/Most of the Time, Week 26	190 48.2%
Q6b: All/Most of the Time, Week 52	215 54.6%
Q6b: Some of the Time, Baseline	154 39.1%
Q6b: Some of the Time, Week 26	134 34%
Q6b: Some of the Time, Week 52	132 33.5%
Q6b: A Little/None of the Time, Baseline	115 29.2%
Q6b: A Little/None of the Time, Week 26	67 17%
Q6b: A Little/None of the Time, Week 52	40 10.2%
Q6b: Missing, Baseline	3 0.8%
Q6b: Missing, Week 26	3 0.8%
Q6b: Missing, Week 52	1 0.3%
Q6c: All/Most of the Time, Baseline	67 17%
Q6c: All/Most of the Time, Week 26	28 7.1%
Q6c: All/Most of the Time, Week 52	53 13.5%
Q6c: Some of the Time, Baseline	162 41.1%
Q6c: Some of the Time, Week 26	102 25.9%
Q6c: Some of the Time, Week 52	107 27.2%
Q6c: A Little/None of the Time, Baseline	159 40.4%
Q6c: A Little/None of the Time, Week 26	261 66.2%
Q6c: A Little/None of the Time, Week 52	227 57.6%
Q6c: Missing, Baseline	6 1.5%
Q6c: Missing, Week 26	3 0.8%
Q6c: Missing, Week 52	1 0.3%
Q7: All/Most of the Time, Baseline	116 29.4%
Q7: All/Most of the Time, Week 26	35 8.9%
Q7: All/Most of the Time, Week 52	43 10.9%
Q7: Some of the Time, Baseline	166 42.1%
Q7: Some of the Time, Week 26	129 32.7%
Q7: Some of the Time, Week 52	119 30.2%
Q7: A Little/None of the Time, Baseline	110 27.9%
Q7: A Little/None of the Time, Week 26	228 57.9%
Q7: A Little/None of the Time, Week 52	226 57.4%
Q7: Missing, Baseline	2 0.5%
Q7: Missing, Week 26	2 0.5%
Q7: Missing, Week 52	0 0%

9. Secondary Outcome

Title	Number of Participants With Change in Concomitant Medication of Osteoarthritis Therapy at Week 52
Description	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.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analysed = participants with baseline and Week 52 data.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	369
Increased Therapy	5 1.3%
Decreased Therapy	2 0.5%
No Change in Therapy	362 91.9%

10. Secondary Outcome

Title	Time Between Initial and Repeat Synvisc-One Treatment
Description	Time Between initial and repeat Synvisc-One Treatment was duration between initial and repeat injection in those participants who received repeat injection.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

ITT population. Number of participants analysed = participants from ITT population who received repeat injection.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	11
Mean (Standard Deviation) [weeks]	38.31 (13.403)

11. Secondary Outcome

Title	Change From Baseline in WOMAC A1 Subscore After Repeat Injection
Description	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).
Time Frame	Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF)

Outcome Measure Data

Analysis Population Description

Repeat Intent to treat population included all participants who were eligible for repeat treatment and received at least one repeat dose of study medication.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	11
Week 1 After Repeat Injection	-12.4 (15.32)
Week 4 After Repeat Injection	-10.1 (13.05)

12. Secondary Outcome

Title	Change From Baseline in WOMAC A Score After Repeat Injection
Description	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).
Time Frame	Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF)

Outcome Measure Data

Analysis Population Description

Repeat Intent to treat population included all participants who were eligible for repeat treatment and received at least one repeat dose of study medication.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	11
Week 1 After Repeat Injection	-4.04 (10.571)
Week 4 After Repeat Injection	-3.05 (13.473)

13. Secondary Outcome

Title	Change From Baseline in WOMAC B Score After Repeat Injection
Description	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).
Time Frame	Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF)

Outcome Measure Data

Analysis Population Description

Repeat intent to treat population.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	11
Week 1 After Repeat Injection	-6.14 (6.034)
Week 4 After Repeat Injection	-3.23 (12.009)

14. Secondary Outcome

Title	Change From Baseline in WOMAC C Score After Repeat Injection
Description	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).
Time Frame	Baseline; Weeks 1, 4 after repeat injection (missing data imputed by LOCF)

Outcome Measure Data

Analysis Population Description

Repeat intent to treat population.

Arm/Group Title	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.
Measure Participants	11
Week 1 After Repeat Injection	-4.08 (7.578)
Week 4 After Repeat Injection	-4.66 (6.005)

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form up to the final follow up visit (up to Week 56) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (From First dose of study drug until the end of study period). Analysis performed on safety population included all participants treated in the study. Data was planned to be reported for systemic and local adverse events separately.
Arm/Group Title	Synvisc-One: Systemic Adverse Event		Synvisc-One: Local Adverse Event
Arm/Group Description	Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain.Systemic adverse events were defined as any adverse event which occurred anywhere other than in the treated joint.		Single 6 mL IA injection of Synvisc-One at Day 0 (Initial Treatment). Participants received repeat injection based on physician's discretion of safety and efficacy at Week 26, 39 or 52 (Repeat treatment). Repeat injection was given if there was no major safety concerns and WOMAC A1 subscore (measurement of pain while walking on flat surface) was between 40-80 mm (at Week 26, 39 or 52) when measured on a 0-100 mm scale, where higher score indicate higher pain. Local adverse events were defined as any adverse event which occurred in the treated joint.
All Cause Mortality
	Synvisc-One: Systemic Adverse Event		Synvisc-One: Local Adverse Event
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Synvisc-One: Systemic Adverse Event		Synvisc-One: Local Adverse Event
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/394 (1.3%)		1/394 (0.3%)
Cardiac disorders
Cardiac arrest	1/394 (0.3%)		0/394 (0%)
Coronary artery disease	1/394 (0.3%)		0/394 (0%)
Infections and infestations
Influenza	1/394 (0.3%)		0/394 (0%)
Urinary tract infection	1/394 (0.3%)		0/394 (0%)
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis	1/394 (0.3%)		0/394 (0%)
Intervertebral disc protrusion	1/394 (0.3%)		0/394 (0%)
Arthritis	0/394 (0%)		1/394 (0.3%)
Nervous system disorders
Cervical myelopathy	1/394 (0.3%)		0/394 (0%)
Myelomalacia	1/394 (0.3%)		0/394 (0%)
Other (Not Including Serious) Adverse Events
	Synvisc-One: Systemic Adverse Event		Synvisc-One: Local Adverse Event
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/394 (5.8%)		22/394 (5.6%)
Gastrointestinal disorders
Constipation	1/394 (0.3%)		0/394 (0%)
Vomiting	1/394 (0.3%)		0/394 (0%)
General disorders
Oedema peripheral	4/394 (1%)		0/394 (0%)
Pain	2/394 (0.5%)		0/394 (0%)
Pyrexia	2/394 (0.5%)		0/394 (0%)
Injection site pain	0/394 (0%)		1/394 (0.3%)
Injection site pruritus	0/394 (0%)		1/394 (0.3%)
Infections and infestations
Cellulitis	1/394 (0.3%)		0/394 (0%)
Influenza	3/394 (0.8%)		0/394 (0%)
Injury, poisoning and procedural complications
Ligament sprain	1/394 (0.3%)		0/394 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/394 (0.5%)		16/394 (4.1%)
Back pain	3/394 (0.8%)		0/394 (0%)
Myalgia	2/394 (0.5%)		0/394 (0%)
Neck pain	1/394 (0.3%)		0/394 (0%)
Pain in extremity	4/394 (1%)		0/394 (0%)
Synovitis	0/394 (0%)		4/394 (1%)
Bursitis	0/394 (0%)		1/394 (0.3%)
Musculoskeletal stiffness	0/394 (0%)		1/394 (0.3%)
Nervous system disorders
Head discomfort	1/394 (0.3%)		0/394 (0%)
Headache	1/394 (0.3%)		0/394 (0%)
Radiculopathy	1/394 (0.3%)		0/394 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/394 (0.3%)		0/394 (0%)
Skin and subcutaneous tissue disorders
Rash	1/394 (0.3%)		0/394 (0%)
Skin hyperpigmentation	1/394 (0.3%)		0/394 (0%)
Swelling face	1/394 (0.3%)		0/394 (0%)
Urticaria	1/394 (0.3%)		0/394 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.