Osteoarthritis
Conditions
Brief summary
Primary Objective: * To evaluate the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 subscore (walking pain) at 26 weeks compared to the Baseline score * To evaluate the safety using the incidence, severity, seriousness, relatedness, and frequency of all treatment emergent Adverse Events (AEs) Secondary Objectives: * To evaluate the change in WOMAC A1 subscore (walking pain) between baseline and weeks 8, and 12 * To evaluate the change in WOMAC A, B and C score between baseline and weeks 8, 12 and 26 * To evaluate the change in Patient Global Assessment (PTGA) score between baseline and weeks 8, 12 and 26 * To evaluate the change in Clinical Observer Global Assessment (COGA) score between baseline and weeks 8, 12 and 26 * To evaluate the change in concomitant Osteoarthritis (OA) therapy over 26 weeks and between baseline and weeks 1, 2, 8, 12 and 26
Detailed description
Duration of study period for each participants was 26-28 weeks.
Interventions
DRUGHylan G-F 20
Intra-articular injection (pre-filled glass syringe)
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: 1. The participants had a diagnosis of OA of the Target Knee confirmed by recent X-Ray (mild to moderate joint space narrowing and/or osteophytes predominant in the tibiofemoral compartment) 2. WOMAC A1 baseline 100 mm Visual Analog Score (VAS) between 40-80 mm (moderate or severe walking pain) in the Target knee 3. Participants with bilateral disease 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 might also be treated with Synvisc® and did not need to meet the Kellgren-Lawrence (KL) grade knee specific inclusion criteria described above. The other criteria applied, and included in safety assessment 4. Pre-menopausal female participants had a negative urine pregnancy test and continue to use a medically acceptable form of contraception for the duration of the study. Otherwise, females had been surgically sterile, or postmenopausal (as documented in medical history) for at least 1 year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Subscore (Walking Pain) at Week 26 | Baseline, Week 26 (missing data imputed by Last Observation Carried Forward [LOCF]) | WOMAC is health status measure questionnaire of twenty-four questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A1 (walking pain) was measured on a scale of 0-100 mm, where lower score represents lower pain and higher score represents higher pain. |
| Overview of Adverse Events (AE) | Up to Week 26 | An AE could be any unfavorable and unintended symptom, sign, disease or condition, or test abnormality whether or not considered related to the investigational product. A serious adverse event (SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAE): AEs that developed/worsened during the 'on treatment period' (from first dose of study drug until the end of study period). Category AE included participant with both serious and non-serious AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Assessment (PTGA) Score | Baseline, Week 8, 12 and 26 (missing data imputed by LOCF) | PTGA (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. Percentage of participants with different categories of PTGA score at baseline, Week 8, 12 and 26 are reported. |
| Change From Baseline in WOMAC A1 Subscore (Walking Pain) at Week 8 and 12 | Baseline, Week 8 and Week 12 (missing data imputed by LOCF) | WOMAC is health status measure questionnaire of twenty-four questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A1 (walking pain) was measured on a scale of 0-100 mm, where lower score represents lower pain and higher score represents higher pain. |
| Percentage of Participants With Change in Concomitant Medication of Osteoarthritis Therapy at Week 26 | Baseline up to Week 26 | 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 1) state. Any change in the therapy (less use of other therapies, more use of other therapies and no change in use of other therapies) during the study was reported. |
| Clinical Observer Global Assessment (COGA) Score | Baseline, Week 8, 12 and 26 (missing data imputed by LOCF) | COGA (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. Percentage of participants with different categories of COGA score at baseline,Week 8, 12 and 26 are reported. |
| Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26 | Baseline, Week 8, 12 and 26 (missing data imputed by LOCF) | WOMAC is health status measure questionnaire of twenty-four questions comprising 3 subscales (pain, stiffness and physical function). Each question was measured on a scale of 0-100 mm where lower score represents lower pain (better condition) and higher score represents higher pain. WOMAC A (measure of pain during walking on a flat surface) was sum of first five items with total score ranging from 0-500 mm, Lower score represents lower pain and higher score represents higher pain. WOMAC B (Stiffness) is the sum of the sixth and seventh item, it is in the range of 0-200 mm. WOMAC C (function) is the sum of the eighth to twenty-forth item, the score is in the range of 0-1700 mm. |
Countries
China
Participant flow
Recruitment details
The study was conducted at 10 centers in China. A total of 237 participants were enrolled between March 09, 2012 and February 28, 2013.
Pre-assignment details
Of 237 enrolled participants 232 participants were treated. 5 participants were excluded from total enrolled (3 participant due to informed consent filled by family, and 2 participant due to no efficacy data after treatment).
Participants by arm
| Arm | Count |
|---|---|
| Synvisc Three IA injections of Synvisc (2.25 ml glass syringe containing 16 mg hylan G-F 20) at intervals of one week. The total duration of observation was 26 weeks. | 237 |
| Total | 237 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 1 |
| Overall Study | Withdrawal by participant | 3 |
Baseline characteristics
| Characteristic | Synvisc |
|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 9.56 |
| Sex: Female, Male Female | 183 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 66 / 237 |
| serious Total, serious adverse events | 4 / 237 |
Outcome results
Primary
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Subscore (Walking Pain) at Week 26
WOMAC is health status measure questionnaire of twenty-four questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A1 (walking pain) was measured on a scale of 0-100 mm, where lower score represents lower pain and higher score represents higher pain.
Time frame: Baseline, Week 26 (missing data imputed by Last Observation Carried Forward [LOCF])
Population: Full Analysis Set (FAS) included all participants who received at least one injection of Synvisc®. 5 participants were excluded from total enrolled (3 participant due to informed consent filled by family, and 2 participant due to no efficacy data after treatment).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Synvisc | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Subscore (Walking Pain) at Week 26 | -33.0 mm | Standard Deviation 17.71 |
p-value: <0.0001Paired t-test
p-value: <0.0001Sign Rank Test
Primary
Overview of Adverse Events (AE)
An AE could be any unfavorable and unintended symptom, sign, disease or condition, or test abnormality whether or not considered related to the investigational product. A serious adverse event (SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAE): AEs that developed/worsened during the 'on treatment period' (from first dose of study drug until the end of study period). Category AE included participant with both serious and non-serious AE.
Time frame: Up to Week 26
Population: Safety Set included all participants who received at least one injection of Synvisc.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synvisc | Overview of Adverse Events (AE) | AEs | 27.8 percentage of participants |
| Synvisc | Overview of Adverse Events (AE) | Treatment-emergent AEs | 27.8 percentage of participants |
| Synvisc | Overview of Adverse Events (AE) | Treatment-emergent SAEs | 1.7 percentage of participants |
| Synvisc | Overview of Adverse Events (AE) | Treatment-emergent AEs Lead to Discontinuation | 0.4 percentage of participants |
Secondary
Change From Baseline in WOMAC A1 Subscore (Walking Pain) at Week 8 and 12
WOMAC is health status measure questionnaire of twenty-four questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A1 (walking pain) was measured on a scale of 0-100 mm, where lower score represents lower pain and higher score represents higher pain.
Time frame: Baseline, Week 8 and Week 12 (missing data imputed by LOCF)
Population: FAS population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Synvisc | Change From Baseline in WOMAC A1 Subscore (Walking Pain) at Week 8 and 12 | Change form baseline at Week 8 | -26.0 mm | Standard Deviation 17.68 |
| Synvisc | Change From Baseline in WOMAC A1 Subscore (Walking Pain) at Week 8 and 12 | Change form baseline at Week 12 | -30.0 mm | Standard Deviation 17.43 |
Secondary
Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26
WOMAC is health status measure questionnaire of twenty-four questions comprising 3 subscales (pain, stiffness and physical function). Each question was measured on a scale of 0-100 mm where lower score represents lower pain (better condition) and higher score represents higher pain. WOMAC A (measure of pain during walking on a flat surface) was sum of first five items with total score ranging from 0-500 mm, Lower score represents lower pain and higher score represents higher pain. WOMAC B (Stiffness) is the sum of the sixth and seventh item, it is in the range of 0-200 mm. WOMAC C (function) is the sum of the eighth to twenty-forth item, the score is in the range of 0-1700 mm.
Time frame: Baseline, Week 8, 12 and 26 (missing data imputed by LOCF)
Population: FAS population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Synvisc | Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26 | WOMAC A: Change from baseline at Week 8 | -92.7 mm | Standard Deviation 71.77 |
| Synvisc | Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26 | WOMAC A: Change from baseline at Week 12 | -109.8 mm | Standard Deviation 73.68 |
| Synvisc | Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26 | WOMAC A: Change from baseline at Week 26 | -121.5 mm | Standard Deviation 77.18 |
| Synvisc | Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26 | WOMAC B: Change from baseline at Week 8 | -28.9 mm | Standard Deviation 37.53 |
| Synvisc | Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26 | WOMAC B: Change from baseline at Week 12 | -34.6 mm | Standard Deviation 38.44 |
| Synvisc | Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26 | WOMAC B: Change from baseline at Week 26 | -36.6 mm | Standard Deviation 39.75 |
| Synvisc | Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26 | WOMAC C: Change from baseline at Week 8 | -270.0 mm | Standard Deviation 252.86 |
| Synvisc | Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26 | WOMAC C: Change from baseline at Week 12 | -325.9 mm | Standard Deviation 258.57 |
| Synvisc | Change From Baseline in WOMAC A, B and C Score at Weeks 8, 12 and 26 | WOMAC C: Change from baseline at Week 26 | -358.4 mm | Standard Deviation 270.48 |
Secondary
Clinical Observer Global Assessment (COGA) Score
COGA (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. Percentage of participants with different categories of COGA score at baseline,Week 8, 12 and 26 are reported.
Time frame: Baseline, Week 8, 12 and 26 (missing data imputed by LOCF)
Population: FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Baseline: Very Poor | 5.6 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 8: Very Well | 5.2 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 26: Poor | 7.8 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 12: Very Well | 7.3 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Baseline: Very Well | 0.0 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Baseline: Well | 1.7 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Baseline: Fair | 35.3 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Baseline: Poor | 57.3 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 8: Well | 42.7 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 8: Fair | 41.8 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 8: Poor | 9.9 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 8: Very Poor | 0.4 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 12: Well | 44.4 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 12: Fair | 41.8 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 12: Poor | 6.0 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 12: Very Poor | 0.4 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 26: Very Well | 9.5 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 26: Well | 47.4 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 26: Fair | 35.3 percentage of participants |
| Synvisc | Clinical Observer Global Assessment (COGA) Score | Week 26: Very Poor | 0.0 percentage of participants |
Secondary
Patient Global Assessment (PTGA) Score
PTGA (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. Percentage of participants with different categories of PTGA score at baseline, Week 8, 12 and 26 are reported.
Time frame: Baseline, Week 8, 12 and 26 (missing data imputed by LOCF)
Population: FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synvisc | Patient Global Assessment (PTGA) Score | Week 8: Very Poor | 0.9 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 12: Very Well | 5.2 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Baseline: Very Well | 0.0 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Baseline: Well | 1.3 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Baseline: Fair | 29.3 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Baseline: Poor | 60.3 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Baseline: Very Poor | 9.1 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 8: Very Well | 4.3 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 8: Well | 41.8 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 8: Fair | 46.1 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 8 : Poor | 6.9 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 12: Well | 44.4 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 12: Fair | 44.0 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 12: Poor | 6.0 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 12: Very Poor | 0.4 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 26: Very Well | 8.2 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 26: Well | 46.6 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 26: Fair | 37.1 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 26: Poor | 7.8 percentage of participants |
| Synvisc | Patient Global Assessment (PTGA) Score | Week 26: Very Poor | 0.4 percentage of participants |
Secondary
Percentage of Participants With Change in Concomitant Medication of Osteoarthritis Therapy at Week 26
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 1) state. Any change in the therapy (less use of other therapies, more use of other therapies and no change in use of other therapies) during the study was reported.
Time frame: Baseline up to Week 26
Population: FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Synvisc | Percentage of Participants With Change in Concomitant Medication of Osteoarthritis Therapy at Week 26 | Required Less Use of Other Therapies | 2.2 percentage participants |
| Synvisc | Percentage of Participants With Change in Concomitant Medication of Osteoarthritis Therapy at Week 26 | Required More Use of Other Therapies | 3.0 percentage participants |
| Synvisc | Percentage of Participants With Change in Concomitant Medication of Osteoarthritis Therapy at Week 26 | Required No Change in Use of Other Therapies | 93.1 percentage participants |
| Synvisc | Percentage of Participants With Change in Concomitant Medication of Osteoarthritis Therapy at Week 26 | Missing | 1.7 percentage participants |