Osteoarthritis, Hip
Conditions
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.
Interventions
DEVICEPlacebo
6 mL injection of phosphate buffered saline
DEVICESynvisc-One (hylan G-F 20)
6-mL IA injection
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
Canada, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 175 |
| 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. | 182 |
| Total | 357 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 10 |
| Overall Study | Lack of Efficacy | 8 | 8 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Other than specified above | 1 | 1 |
| Overall Study | Randomized but not treated | 3 | 2 |
| Overall Study | Technical problems | 2 | 0 |
| Overall Study | Withdrawal by Subject | 17 | 22 |
Baseline characteristics
| Characteristic | Placebo | Synvisc-One | Total |
|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 8.8 | 60.8 years STANDARD_DEVIATION 10 | 60.3 years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 105 Participants | 106 Participants | 211 Participants |
| Sex: Female, Male Male | 70 Participants | 76 Participants | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 172 | 43 / 180 |
| serious Total, serious adverse events | 15 / 172 | 10 / 180 |
Outcome results
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.
Time frame: From baseline to Week 26
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Subscore (Walking Pain) Over 26 Weeks | -2.26 units on a scale | Standard Error 0.17 |
| Synvisc-One | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Subscore (Walking Pain) Over 26 Weeks | -2.19 units on a scale | Standard Error 0.16 |
Comparison: Synvisc-One group was compared to placebo group using mixed model for repeated measures (MMRM) approach assuming missing data at random (MAR).p-value: =0.746295% CI: [-0.38, 0.52]Mixed Models Analysis
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.
Time frame: From baseline to Week 26
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient Global Self-Assessment (PTGA) Score Over 26 Weeks | -2.06 units on a scale | Standard Error 0.17 |
| Synvisc-One | Change From Baseline in Patient Global Self-Assessment (PTGA) Score Over 26 Weeks | -2.00 units on a scale | Standard Error 0.16 |
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.
Time frame: From Baseline to Week 26
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in WOMAC A Score Over 26 Weeks | -2.26 units on a scale | Standard Error 0.16 |
| Synvisc-One | Change From Baseline in WOMAC A Score Over 26 Weeks | -2.19 units on a scale | Standard Error 0.16 |
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.
Time frame: From Baseline to Week 26
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of WOMAC A1 Responder Over 26 Weeks | 45.71 Percentage of participants |
| Synvisc-One | Percentage of WOMAC A1 Responder Over 26 Weeks | 45.05 Percentage of participants |