A Study of the Safety and Effectiveness of Synvisc-One® (Hylan G-F 20) in Patients With Primary Osteoarthritis of the Hip

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01618708
• Collaborator: (none)
• Enrollment: 357
• Locations: 48
• Arms: 2
• Duration (Months): 33
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study was to demonstrate any changes in assessments of pain for participants receiving Synvisc-One compared to control.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Hip	Device: Synvisc-One (hylan G-F 20); Device: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 357 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pivotal, Multicenter, Double Blind Study of the Safety and Effectiveness of Synvisc-One® (Hylan G-F 20) in Patients With Mild to Moderate Primary Osteoarthritis of the Hip
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Synvisc-One Single intraarticular (IA) injection of Synvisc-One (48 mg of Hylan G-F 20 polymer) at Day 1. Participants were observed for 26 weeks in follow up period.	Device: Synvisc-One (hylan G-F 20); 6-mL IA injection
Placebo Comparator: Placebo Single IA injection of placebo matched to Synvisc-One at Day 1. Participants were observed for 26 weeks in follow up period.	Device: Placebo; 6 mL injection of phosphate buffered saline

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Subscore (Walking Pain) Over 26 Weeks [From baseline to Week 26]

   WOMAC Numerical Rating Scale (NRS) 3.1 questionnaire is a health status measure questionnaire of 24 questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A1 (measure of pain during walking on a flat surface) was measured on 11-point (NRS) ranging from 0 (none) to 10 (extreme), where lower score represents lower pain and higher score represents higher pain.

Secondary Outcome Measures

1. Change From Baseline in WOMAC A Score Over 26 Weeks [From Baseline to Week 26]

   WOMAC NRS 3.1 questionnaire is a health status measure questionnaire of 24 questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A (measure of pain) was measured on 11-point NRS ranging from 0 (none) to 10 (extreme), where lower score represents lower pain and higher score represents higher pain.

2. Change From Baseline in Patient Global Self-Assessment (PTGA) Score Over 26 Weeks [From baseline to Week 26]

   PTGA (self-assessment of target hip osteoarthritis condition) was measured using the 11-point NRS ranging from 0 (none) to 10 (extreme), where lower score represents very well condition and higher score represents very poor condition.

3. Percentage of WOMAC A1 Responder Over 26 Weeks [From Baseline to Week 26]

   WOMAC A1 responder rate defined as ≥2 point improvement on 11-point NRS Scale, generalized estimating equations modeling was used for the analysis of WOMAC A1 responders.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The participant had symptomatic osteoarthritis (OA) in the target joint

• The participant had a diagnosis of primary OA of the hip at Screening according to the American College of Rheumatology (ACR) Criteria

• The participant, if female and of childbearing potential, must had a negative pregnancy test and had taken oral contraceptives for at least 1 month prior to treatment and continued for the duration of the study (up to and including the final study visit), or agreed to use 2 forms of contraception (e.g., condoms plus spermatocide), otherwise females must be surgically sterile, or postmenopausal for at least 1 year

Exclusion Criteria:

• The participant had symptomatic OA in the contralateral hip with a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 numerical rating scale (NRS) score of ≥ 4 at Screening (symptomatic OA with a WOMAC A1 NRS score of 0-3 in the contralateral hip was allowed)

• The participant if a woman was pregnant, lactating, or unwilling to use adequate contraception

• The participant had prior viscosupplementation therapy in the target hip joint within 26 weeks of Screening

• The participant had a known history of hypersensitivity to avian protein or any components of hyaluronan-based injection devices

• The participant had a known history of hypersensitivity to steroids, lidocaine, and/or acetaminophen

• The participant had a known history of hypersensitivity to injected contrast agent at a previous radiological examination (e.g., computed tomography [CT] scan, angiogram, etc.), or known history of hypersensitivity to shellfish or iodine, or any other impediment to the hip injection procedure

• The participant had active infection in the area of the injection site

• The participant had any major surgery, arthroplasty or arthroscopy in the target hip or lower extremities within 26 weeks of Screening, or planned surgery in the lower extremities throughout the duration of the study infectious complications

• The participant used an investigational drug, device or biologic within 12 weeks of Screening

• The participant had any significant medical condition that the Investigator feels would interfere with study evaluations and study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840025	Burmingham	Alabama	United States	35216
2	Investigational Site Number 840042	Phoenix	Arizona	United States	85016
3	Investigational Site Number 840056	Phoenix	Arizona	United States	85027
4	Investigational Site Number 840004	Tucson	Arizona	United States	85712
5	Investigational Site Number 840023	Covina	California	United States	91723
6	Investigational Site Number 840058	La Mesa	California	United States	91942
7	Investigational Site Number 840022	Santa Monica	California	United States	90904
8	Investigational Site Number 840050	Farmington	Connecticut	United States	06033
9	Investigational Site Number 840027	Stamford	Connecticut	United States	06905
10	Investigational Site Number 840051	Waterbury	Connecticut	United States	06708
11	Investigational Site Number 840011	Bradenton	Florida	United States	84020
12	Investigational Site Number 840036	Fort Lauderdale	Florida	United States	33316
13	Investigational Site Number 840017	Jupiter	Florida	United States	33458
14	Investigational Site Number 840038	New Port Richey	Florida	United States	34652
15	Investigational Site Number 840041	Pensacola	Florida	United States	32504
16	Investigational Site Number 840047	Sarasota	Florida	United States	34232
17	Investigational Site Number 840049	South Miami	Florida	United States	33134
18	Investigational Site Number 840039	Marietta	Georgia	United States	30060
19	Investigational Site Number 840005	Meridian	Idaho	United States	83642
20	Investigational Site Number 840002	Chicago	Illinois	United States	60611
21	Investigational Site Number 840043	Wichita	Kansas	United States	67203
22	Investigational Site Number 840012	Lexington	Kentucky	United States	40509
23	Investigational Site Number 840033	Traverse City	Michigan	United States	49648
24	Investigational Site Number 840037	St. Louis	Missouri	United States	63128
25	Investigational Site Number 840007	Reno	Nevada	United States	89502
26	Investigational Site Number 840048	Egg Harbor Township	New Jersey	United States	08234
27	Investigational Site Number 840024	Amherst	New York	United States	14226
28	Investigational Site Number 840029	Hartsdale	New York	United States	10530
29	Investigational Site Number 840014	Rochester	New York	United States	14609
30	Investigational Site Number 840044	Asheville	North Carolina	United States	28801
31	Investigational Site Number 840028	Raleigh	North Carolina	United States	27612
32	Investigational Site Number 840045	Wilmington	North Carolina	United States	28401
33	Investigational Site Number 840046	Columbus	Ohio	United States	43213
34	Investigational Site Number 840013	Altoona	Pennsylvania	United States	16635
35	Investigational Site Number 840055	Philadelphia	Pennsylvania	United States	19107
36	Investigational Site Number 840018	Reading	Pennsylvania	United States	19611
37	Investigational Site Number 840026	Mt. Pleasant	South Carolina	United States	29464
38	Investigational Site Number 840052	Memphis	Tennessee	United States	38163
39	Investigational Site Number 840054	Austin	Texas	United States	78751
40	Investigational Site Number 840040	Bedford	Texas	United States	76021
41	Investigational Site Number 840010	Dallas	Texas	United States	75235
42	Investigational Site Number 840009	Draper	Utah	United States	84020
43	Investigational Site Number 840032	Salt Lake City	Utah	United States	84107
44	Investigational Site Number 840016	Charlottesville	Virginia	United States	22901
45	Investigational Site Number 840003	Seattle	Washington	United States	98166
46	Investigational Site Number 124091	London		Canada	N6C 4R3
47	Investigational Site Number 124093	Montreal		Canada	H4N 3C5
48	Investigational Site Number 124092	Sherbrooke		Canada	J1H 1Z1

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Medical Monitor, Genzyme, a Sanofi Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01618708
• Other Study ID Numbers: SYNV04910; EFC12791
• First Posted: Jun 13, 2012
• Last Update Posted: Jul 11, 2016
• Last Verified: May 1, 2016

• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Hip; Hylan

Study Results

Participant Flow

Recruitment Details	The study was conducted at 42 centers in the US and Canada. A total of 1113 participants were screened between 05 September 2012 and 21 November 2014.
Pre-assignment Detail	Of 1113 screened participants, 33 were re-screened, 357 were randomized and 741 were screen failures. Screen failures were mainly due to inclusion criteria not met and exclusion criteria met.

Arm/Group Title	Placebo	Synvisc-One
Arm/Group Description	Single 6 mL intraarticular (IA) injection of placebo matched to Synvisc-One (phosphate buffered saline) at Day 1. Participants were observed for 26 weeks in follow up period.	Single 6 mL IA injection of Synvisc-One (48 mg of Hylan G-F 20 polymer) at Day 1. Participants were observed for 26 weeks in follow up period.
Period Title: Overall Study
STARTED	175	182
Treated	172	180
COMPLETED	131	136
NOT COMPLETED	44	46

Baseline Characteristics

Arm/Group Title	Placebo	Synvisc-One	Total
Arm/Group Description	Single 6 mL IA injection of placebo matched to Synvisc-One (phosphate buffered saline) at Day 1. Participants were observed for 26 weeks in follow up period.	Single 6 mL IA injection of Synvisc-One (48 mg of Hylan G-F 20 polymer) at Day 1. Participants were observed for 26 weeks in follow up period.	Total of all reporting groups
Overall Participants	175	182	357
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.8 (8.8)	60.8 (10.0)	60.3 (9.4)
Sex: Female, Male (Count of Participants)
Female	105 60%	106 58.2%	211 59.1%
Male	70 40%	76 41.8%	146 40.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Subscore (Walking Pain) Over 26 Weeks
Description	WOMAC Numerical Rating Scale (NRS) 3.1 questionnaire is a health status measure questionnaire of 24 questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A1 (measure of pain during walking on a flat surface) was measured on 11-point (NRS) ranging from 0 (none) to 10 (extreme), where lower score represents lower pain and higher score represents higher pain.
Time Frame	From baseline to Week 26

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of placebo matched to Synvisc-One (phosphate buffered saline) at Day 1. Participants were observed for 26 weeks in follow up period.	Single 6 mL IA injection of Synvisc-One (48 mg of Hylan G-F 20 polymer) at Day 1. Participants were observed for 26 weeks in follow up period.
Measure Participants	175	182
Least Squares Mean (Standard Error) [units on a scale]	-2.26 (0.17)	-2.19 (0.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Synvisc-One
	Comments	Synvisc-One group was compared to placebo group using mixed model for repeated measures (MMRM) approach assuming missing data at random (MAR).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	= 0.7462
	Comments	Threshold for significance at 0.05 level
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean difference
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; -0.38 to 0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo vs Synvisc-One

2. Secondary Outcome

Title	Change From Baseline in WOMAC A Score Over 26 Weeks
Description	WOMAC NRS 3.1 questionnaire is a health status measure questionnaire of 24 questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A (measure of pain) was measured on 11-point NRS ranging from 0 (none) to 10 (extreme), where lower score represents lower pain and higher score represents higher pain.
Time Frame	From Baseline to Week 26

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of placebo matched to Synvisc-One at Day 1. Participants were observed for 26 weeks in follow up period.	Single 6 mL IA injection of Synvisc-One (48 mg of Hylan G-F 20 polymer) at Day 1. Participants were observed for 26 weeks in follow up period.
Measure Participants	175	182
Least Squares Mean (Standard Error) [units on a scale]	-2.26 (0.16)	-2.19 (0.16)

3. Secondary Outcome

Title	Change From Baseline in Patient Global Self-Assessment (PTGA) Score Over 26 Weeks
Description	PTGA (self-assessment of target hip osteoarthritis condition) was measured using the 11-point NRS ranging from 0 (none) to 10 (extreme), where lower score represents very well condition and higher score represents very poor condition.
Time Frame	From baseline to Week 26

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of placebo matched to Synvisc-One (phosphate buffered saline) at Day 1. Participants were observed for 26 weeks in follow up period.	Single 6 mL IA injection of Synvisc-One (48 mg of Hylan G-F 20 polymer) at Day 1. Participants were observed for 26 weeks in follow up period.
Measure Participants	175	182
Least Squares Mean (Standard Error) [units on a scale]	-2.06 (0.17)	-2.00 (0.16)

4. Secondary Outcome

Title	Percentage of WOMAC A1 Responder Over 26 Weeks
Description	WOMAC A1 responder rate defined as ≥2 point improvement on 11-point NRS Scale, generalized estimating equations modeling was used for the analysis of WOMAC A1 responders.
Time Frame	From Baseline to Week 26

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo	Synvisc-One
Arm/Group Description	Single 6 mL IA injection of placebo matched to Synvisc-One (phosphate buffered saline) at Day 1. Participants were observed for 26 weeks in follow up period.	Single 6 mL IA injection of Synvisc-One (48 mg of Hylan G-F 20 polymer) at Day 1. Participants were observed for 26 weeks in follow up period.
Measure Participants	175	182
Number [Percentage of participants]	45.71 26.1%	45.05 24.8%

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 26) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported adverse events are treatment-emergent adverse events that is any AE that started during or after the first dose of study drug. Safety population defined as all randomized participants who received any study drug or part of treatment administration.
Arm/Group Title	Placebo		Synvisc-One
Arm/Group Description	Single 6 mL IA injection of placebo matched to Synvisc-One (phosphate buffered saline) at Day 1. Participants were observed for 26 weeks in follow up period.		Single 6 mL IA injection of Synvisc-One (48 mg of Hylan G-F 20 polymer) at Day 1. Participants were observed for 26 weeks in follow up period.
All Cause Mortality
	Placebo		Synvisc-One
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Synvisc-One
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/172 (8.7%)		10/180 (5.6%)
Cardiac disorders
Atrial fibrillation	0/172 (0%)		1/180 (0.6%)
Cardiac failure congestive	0/172 (0%)		1/180 (0.6%)
Myocardial infarction	0/172 (0%)		1/180 (0.6%)
Congenital, familial and genetic disorders
Intracranial lipoma	1/172 (0.6%)		0/180 (0%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	0/172 (0%)		1/180 (0.6%)
General disorders
Non-cardiac chest pain	1/172 (0.6%)		0/180 (0%)
Hepatobiliary disorders
Bile duct stone	1/172 (0.6%)		0/180 (0%)
Cholecystitis acute	1/172 (0.6%)		0/180 (0%)
Injury, poisoning and procedural complications
Humerus fracture	0/172 (0%)		1/180 (0.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/172 (2.3%)		0/180 (0%)
Back pain	0/172 (0%)		1/180 (0.6%)
Joint stiffness	1/172 (0.6%)		0/180 (0%)
Osteoarthritis	4/172 (2.3%)		2/180 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	0/172 (0%)		1/180 (0.6%)
Pancreatic carcinoma	1/172 (0.6%)		0/180 (0%)
Prostate cancer	0/172 (0%)		1/180 (0.6%)
Psychiatric disorders
Anxiety	0/172 (0%)		1/180 (0.6%)
Confusional state	1/172 (0.6%)		0/180 (0%)
Disorientation	1/172 (0.6%)		0/180 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/172 (0.6%)		0/180 (0%)
Pulmonary mass	1/172 (0.6%)		0/180 (0%)
Surgical and medical procedures
Obesity surgery	1/172 (0.6%)		0/180 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Synvisc-One
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/172 (19.2%)		43/180 (23.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	20/172 (11.6%)		32/180 (17.8%)
Nervous system disorders
Headache	14/172 (8.1%)		13/180 (7.2%)

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.