A Study of the Safety and Effectiveness of Synvisc-One® (... | NCT01618708

ID	Type	Description	Link
EFC12791	Other Identifier	Sanofi

Status Module

Label	Type	Description	Intervention Names
Synvisc-One	Experimental	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)
Placebo	Placebo Comparator	Single IA injection of placebo matched to Synvisc-One at Day 1. Participants were observed for 26 weeks in follow up period.	Device: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Synvisc-One (hylan G-F 20)	Device	6-mL IA injection	Synvisc-One
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Subscore (Walking Pain) Over 26 Weeks	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.	From baseline to Week 26

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in WOMAC A Score Over 26 Weeks	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.	From Baseline to Week 26

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Medical Monitor	Genzyme, a Sanofi Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 840025		Burmingham	Alabama	35216	United States
Investigational Site Number 840042

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	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.
FG001	Synvisc-One

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Subscore (Walking Pain) Over 26 Weeks

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.

ITT population.

Posted

Least Squares Mean

Standard Error

units on a scale

From baseline to Week 26

ID	Title	Description
OG000	Placebo	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.
OG001	Synvisc-One	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.

Units	Counts
Participants	OG000175 OG001182

Title

Denominators

Categories

Title	Measurements
	OG000-2.26± 0.17 OG001-2.19± 0.16

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Synvisc-One group was compared to placebo group using mixed model for repeated measures (MMRM) approach assuming missing data at random (MAR).	Mixed Models Analysis		= 0.7462	Threshold for significance at 0.05 level	Least Squares (LS) Mean difference	0.07			2-Sided	95	-0.38	0.52			Placebo vs Synvisc-One	No	Superiority or Other

Secondary

Change From Baseline in WOMAC A Score Over 26 Weeks

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.

ITT population.

Posted

Least Squares Mean

Standard Error

units on a scale

From Baseline to Week 26

ID	Title	Description
OG000	Placebo	Single 6 mL IA injection of placebo matched to Synvisc-One at Day 1. Participants were observed for 26 weeks in follow up period.
OG001	Synvisc-One	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.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Patient Global Self-Assessment (PTGA) Score Over 26 Weeks

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.

ITT population.

Posted

Least Squares Mean

Standard Error

units on a scale

From baseline to Week 26

ID	Title	Description
OG000	Placebo	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.
OG001	Synvisc-One	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.

Units	Counts
Participants	OG000

Secondary

Percentage of WOMAC A1 Responder Over 26 Weeks

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.

ITT population.

Posted

Number

Percentage of participants

From Baseline to Week 26

ID	Title	Description
OG000	Placebo	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.
OG001	Synvisc-One	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.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected172 at risk EG0011 affected180 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected172 at risk EG0011 affected180 at risk
Myocardial infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected172 at risk EG0011 affected180 at risk
Intracranial lipoma	Congenital, familial and genetic disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected172 at risk EG0010 affected180 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected172 at risk EG0011 affected180 at risk
Non-cardiac chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected172 at risk EG0010 affected180 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected172 at risk EG0010 affected180 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected172 at risk EG0010 affected180 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected172 at risk EG0011 affected180 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected172 at risk EG0010 affected180 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected172 at risk EG0011 affected180 at risk
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected172 at risk EG0010 affected180 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected172 at risk EG0012 affected180 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected172 at risk EG0011 affected180 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected172 at risk EG0010 affected180 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected172 at risk EG0011 affected180 at risk
Anxiety	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected172 at risk EG0011 affected180 at risk
Confusional state	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected172 at risk EG0010 affected180 at risk
Disorientation	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected172 at risk EG0010 affected180 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected172 at risk EG0010 affected180 at risk
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected172 at risk EG0010 affected180 at risk
Obesity surgery	Surgical and medical procedures	MedDRA 18.0	Systematic Assessment	EG0001 affected172 at risk EG0010 affected180 at risk

ID	Term
D010003	Osteoarthritis
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases

ID	Title	Description
BG000	Placebo	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.
BG001	Synvisc-One	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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	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.			15	172	33	172
EG001	Synvisc-One	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.			10	180	43	180