Osteoarthritis of the Knee
Conditions
Brief summary
The purpose of this study is to determine if a single or repeat intra-articular injection of Gel-200 is safe and effective in subjects with symptomatic osteoarthritis of the knee and to determine if original SI-6606/01 Gel-200 therapy is durable beyond the original study.
Interventions
DEVICEGel-200
Single Intra-articular Injection
Sponsors
Seikagaku Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Previous participation in study SI-6606/01.
Exclusion criteria
* Female subjects who are pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Systemic and Local Adverse Events Following a Single or Repeat Intra-articular Injection of Gel-200 | 13 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Visual Analog Scale (VAS) (Pain Subscore) | Baseline and Week 13 | Observed WOMAC pain subscore on VAS of 100 mm.; 0 mm meaning no pain; 100 mm meaning extreme pain. Improved score from baseline to week 13 were calculated as baseline minus week 13. |
| Improvement From Baseline in WOMAC VAS (Stiffness Subscore) | Baseline and Week 13 | Observed WOMAC stiffness subscore on Visual Analog Scale (VAS) of 100 mm; 0 mm meaning no stiffness; 100 mm meaning extreme stiffness. Improved score from baseline to week 13 were calculated as baseline minus week 13. |
| Improvement From Baseline in WOMAC VAS (Physical Function Subscore) | Baseline and Week 13 | Observed WOMAC physical function subscore on Visual Analog Scale (VAS) of 100 mm; 0 mm meaning no difficulty; 100 mm meaning extreme difficulty. Improved score from baseline to week 13 were calculated as baseline minus week 13. |
| Improvement From Baseline in WOMAC VAS (Total Score) | Baseline and Week 13 | Observed all WOMAC mean scores on Visual Analog Scale (VAS) of 100 mm; a total of WOMAC pain, stiffness, and physical function subscores. Improved score from baseline to week 13 were calculated as baseline minus week 13. |
| Outcome Measures in Rheumatology Artthritis Clinical Trials (OMERACT) - and the Osteoarthritis Research Society International (OARSI) Response | Weeks 13 | Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) strict responses defined by improvements from baseline in WOMAC pain or physical function subscore ≥50% with absolute changes ≥20 mm (termed strict responders), or ≥20% with absolute changes ≥10mm in 2 of 3 measures of WOMAC pain or physical function subscore or subject global evaluations (termed responders). |
| Improvement From Baseline in Subject Global Evaluations | Baseline and Week 13 | Observed subject evaluations on Visual Analog Scale (VAS) of 100 mm; 0 mm meaning excellent feeling in knee joint; 100 mm meaning poor feeling in knee joint. Improved score from baseline to week 13 were calculated as baseline minus week 13. |
| Improvement From Baseline in Physician Global Evaluations | Baseline and Week 13 | Observed physician evaluations on Visual Analog Scale (VAS) of 100 mm; 0 mm meaning excellent feeling in knee joint; 100 mm meaning poor feeling in knee joint. Improved score from baseline to week 13 were calculated as baseline minus week 13. |
| Acetaminophen Consumption | Week 9 to Week 13 | Weekly mean acetaminophen consumption between weeks 9 and 13. |
Countries
United States
Participant flow
Pre-assignment details
A total of 202 patients were entered.
Participants by arm
| Arm | Count |
|---|---|
| 2Gel-200 Patients already received 1 single dose of Gel-200 (3 mL) and followed up for 13 weeks in previous study(NCT00449696). After completion of previous study, patients entered this study and received 1 single dose of Gel-200 (3mL) intra-articular injection again into knee joint. | 122 |
| 1PBS1Gel-200 Patients already received 1 single dose of Phosphate Buffered Saline (PBS) placebo (3 mL) and followed up for 13 weeks in previous study (NCT00449696). After completion of previous study, patients entered this study and received 1 single dose of Gel-200 (3mL) intra-articular injection into knee joint. | 74 |
| Total | 196 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Others | 2 | 3 |
| Overall Study | Other Treatment Required | 5 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | 1PBS1Gel-200 | Total | 2Gel-200 |
|---|---|---|---|
| Age Continuous | 61.6 years STANDARD_DEVIATION 10.5 | 61.4 years STANDARD_DEVIATION 10.35 | 61.4 years STANDARD_DEVIATION 10.29 |
| Body Mass Index (BMI) | 29.1 kilograms/meters square STANDARD_DEVIATION 4.01 | 28.8 kilograms/meters square STANDARD_DEVIATION 4.09 | 28.6 kilograms/meters square STANDARD_DEVIATION 4.14 |
| Physician Global Evaluations | 62.6 scores on a scale STANDARD_DEVIATION 20.51 | 61.3 scores on a scale STANDARD_DEVIATION 18.29 | 60.5 scores on a scale STANDARD_DEVIATION 16.85 |
| Region of Enrollment United States | 74 participants | 196 participants | 122 participants |
| Sex: Female, Male Female | 48 Participants | 122 Participants | 74 Participants |
| Sex: Female, Male Male | 26 Participants | 74 Participants | 48 Participants |
| Subject Global Evaluations | 68.2 scores on a scale STANDARD_DEVIATION 18.85 | 66.9 scores on a scale STANDARD_DEVIATION 20.7 | 66.1 scores on a scale STANDARD_DEVIATION 21.81 |
| WOMAC VAS Pain Subscore | 69.9 Scores on a scale STANDARD_DEVIATION 15.13 | 69.5 Scores on a scale STANDARD_DEVIATION 15.53 | 69.4 Scores on a scale STANDARD_DEVIATION 15.82 |
| WOMAC VAS Physical Function Subcore | 69.9 scores on a scale STANDARD_DEVIATION 16.35 | 68.7 scores on a scale STANDARD_DEVIATION 17.35 | 68.0 scores on a scale STANDARD_DEVIATION 17.96 |
| WOMAC VAS Stiffness Subscore | 70.7 scores on a scale STANDARD_DEVIATION 18.4 | 70.1 scores on a scale STANDARD_DEVIATION 18.3 | 69.7 scores on a scale STANDARD_DEVIATION 18.31 |
| WOMAC VAS Total Score | 69.9 scores on a scale STANDARD_DEVIATION 15.79 | 69.0 scores on a scale STANDARD_DEVIATION 16.58 | 68.4 scores on a scale STANDARD_DEVIATION 17.07 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 125 | 27 / 74 |
| serious Total, serious adverse events | 3 / 125 | 1 / 74 |
Outcome results
Primary
Occurrence of Systemic and Local Adverse Events Following a Single or Repeat Intra-articular Injection of Gel-200
Time frame: 13 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2Gel-200 | Occurrence of Systemic and Local Adverse Events Following a Single or Repeat Intra-articular Injection of Gel-200 | 68 participants |
| 1PBS1Gel-200 | Occurrence of Systemic and Local Adverse Events Following a Single or Repeat Intra-articular Injection of Gel-200 | 43 participants |
p-value: >0.1Fisher Exact
Secondary
Acetaminophen Consumption
Weekly mean acetaminophen consumption between weeks 9 and 13.
Time frame: Week 9 to Week 13
Population: ITT population was used for analysis. 3 patients with 2Gel-200 were removed from ITT population analysis and baseline because of no post treatment data according to a pre-specified rule. These data were submitted to FDA.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2Gel-200 | Acetaminophen Consumption | 1677.4 milligrams | Standard Deviation 3135.8 |
| 1PBS1Gel-200 | Acetaminophen Consumption | 1822.5 milligrams | Standard Deviation 2768.22 |
Secondary
Improvement From Baseline in Physician Global Evaluations
Observed physician evaluations on Visual Analog Scale (VAS) of 100 mm; 0 mm meaning excellent feeling in knee joint; 100 mm meaning poor feeling in knee joint. Improved score from baseline to week 13 were calculated as baseline minus week 13.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 3 patients with 2Gel-200 were removed from ITT population analysis and baseline because of no post treatment data according to a pre-specified rule. These data were submitted to FDA.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2Gel-200 | Improvement From Baseline in Physician Global Evaluations | 27.4 millimeters | Standard Deviation 25.08 |
| 1PBS1Gel-200 | Improvement From Baseline in Physician Global Evaluations | 27.4 millimeters | Standard Deviation 27.15 |
Comparison: One-sample 2 sided t-test of change from baseline within 2Gel-200 group; no between-group test was performed.p-value: <0.0001t-test, 2 sided
Comparison: One-sample 2 sided t-test of change from baseline within 1PBS1Gel-200 group; no between-group test was performed.p-value: <0.0001t-test, 2 sided
Secondary
Improvement From Baseline in Subject Global Evaluations
Observed subject evaluations on Visual Analog Scale (VAS) of 100 mm; 0 mm meaning excellent feeling in knee joint; 100 mm meaning poor feeling in knee joint. Improved score from baseline to week 13 were calculated as baseline minus week 13.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 3 patients with 2Gel-200 were removed from ITT population analysis and baseline because of no post treatment data according to a pre-specified rule. These data were submitted to FDA.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2Gel-200 | Improvement From Baseline in Subject Global Evaluations | 29.8 millimeters | Standard Deviation 30.76 |
| 1PBS1Gel-200 | Improvement From Baseline in Subject Global Evaluations | 33.4 millimeters | Standard Deviation 26.24 |
Comparison: One-sample 2 sided t-test of change from baseline within 2Gel-200 group; no between-group test was performed.p-value: <0.0001t-test, 2 sided
Comparison: One-sample 2 sided t-test of change from baseline within 1PBS1Gel-200 group; no between-group test was performed.p-value: <0.0001t-test, 2 sided
Secondary
Improvement From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Visual Analog Scale (VAS) (Pain Subscore)
Observed WOMAC pain subscore on VAS of 100 mm.; 0 mm meaning no pain; 100 mm meaning extreme pain. Improved score from baseline to week 13 were calculated as baseline minus week 13.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 3 patients with 2Gel-200 were removed from ITT population analysis and baseline because of no post treatment data according to a pre-specified rule. These data were submitted to FDA.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2Gel-200 | Improvement From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Visual Analog Scale (VAS) (Pain Subscore) | 32.3 millimeters | Standard Deviation 22.68 |
| 1PBS1Gel-200 | Improvement From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Visual Analog Scale (VAS) (Pain Subscore) | 35.4 millimeters | Standard Deviation 22.97 |
Comparison: One-sample 2 sided t-test of change from baseline within 2Gel-200 group; no between-group test was performed.p-value: <0.0001t-test, 2 sided
Comparison: One-sample 2 sided t-test of change from baseline within 1PBS1Gel-200 group; no between-group test was performed.p-value: <0.0001t-test, 2 sided
Secondary
Improvement From Baseline in WOMAC VAS (Physical Function Subscore)
Observed WOMAC physical function subscore on Visual Analog Scale (VAS) of 100 mm; 0 mm meaning no difficulty; 100 mm meaning extreme difficulty. Improved score from baseline to week 13 were calculated as baseline minus week 13.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 3 patients with 2Gel-200 were removed from ITT population analysis and baseline because of no post treatment data according to a pre-specified rule. These data were submitted to FDA.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2Gel-200 | Improvement From Baseline in WOMAC VAS (Physical Function Subscore) | 30.1 millimeters | Standard Deviation 22.85 |
| 1PBS1Gel-200 | Improvement From Baseline in WOMAC VAS (Physical Function Subscore) | 34.4 millimeters | Standard Deviation 24.04 |
Comparison: One-sample 2 sided t-test of change from baseline within 2Gel-200 group; no between-group test was performed.p-value: <0.0001t-test, 2 sided
Comparison: One-sample 2 sided t-test of change from baseline within 1PBS1Gel-200 group; no between-group test was performed.p-value: <0.0001t-test, 2 sided
Secondary
Improvement From Baseline in WOMAC VAS (Stiffness Subscore)
Observed WOMAC stiffness subscore on Visual Analog Scale (VAS) of 100 mm; 0 mm meaning no stiffness; 100 mm meaning extreme stiffness. Improved score from baseline to week 13 were calculated as baseline minus week 13.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 3 patients with 2Gel-200 were removed from ITT population analysis and baseline because of no post treatment data according to a pre-specified rule. These data were submitted to FDA.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2Gel-200 | Improvement From Baseline in WOMAC VAS (Stiffness Subscore) | 29.0 millimeters | Standard Deviation 24.95 |
| 1PBS1Gel-200 | Improvement From Baseline in WOMAC VAS (Stiffness Subscore) | 34.5 millimeters | Standard Deviation 25.27 |
Comparison: One-sample 2 sided t-test of change from baseline within 2Gel-200 group; no between-group test was performed.p-value: <0.0001t-test, 2 sided
Comparison: One-sample 2 sided t-test of change from baseline within 1PBS1Gel-200 group; no between-group test was performed.p-value: <0.0001t-test, 2 sided
Secondary
Improvement From Baseline in WOMAC VAS (Total Score)
Observed all WOMAC mean scores on Visual Analog Scale (VAS) of 100 mm; a total of WOMAC pain, stiffness, and physical function subscores. Improved score from baseline to week 13 were calculated as baseline minus week 13.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 3 patients with 2Gel-200 were removed from ITT population analysis and baseline because of no post treatment data according to a pre-specified rule. These data were submitted to FDA.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2Gel-200 | Improvement From Baseline in WOMAC VAS (Total Score) | 30.4 millimeters | Standard Deviation 22.6 |
| 1PBS1Gel-200 | Improvement From Baseline in WOMAC VAS (Total Score) | 34.6 millimeters | Standard Deviation 23.66 |
Comparison: One-sample 2 sided t-test of change from baseline within 2Gel-200 group; no between-group test was performed..p-value: <0.0001t-test, 2 sided
Comparison: One-sample 2 sided t-test of change from baseline within 1PBS1Gel-200 group; no between-group test was performed.p-value: <0.0001t-test, 2 sided
Secondary
Outcome Measures in Rheumatology Artthritis Clinical Trials (OMERACT) - and the Osteoarthritis Research Society International (OARSI) Response
Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) strict responses defined by improvements from baseline in WOMAC pain or physical function subscore ≥50% with absolute changes ≥20 mm (termed strict responders), or ≥20% with absolute changes ≥10mm in 2 of 3 measures of WOMAC pain or physical function subscore or subject global evaluations (termed responders).
Time frame: Weeks 13
Population: ITT population was used for analysis. 3 patients with 2Gel-200 were removed from ITT population analysis and baseline because of no post treatment data according to a pre-specified rule. These data were submitted to FDA.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2Gel-200 | Outcome Measures in Rheumatology Artthritis Clinical Trials (OMERACT) - and the Osteoarthritis Research Society International (OARSI) Response | Participants who met strict responders at week 13 | 58.0 Percentage of Participants |
| 2Gel-200 | Outcome Measures in Rheumatology Artthritis Clinical Trials (OMERACT) - and the Osteoarthritis Research Society International (OARSI) Response | Participants who met responders at week 13 | 75.0 Percentage of Participants |
| 1PBS1Gel-200 | Outcome Measures in Rheumatology Artthritis Clinical Trials (OMERACT) - and the Osteoarthritis Research Society International (OARSI) Response | Participants who met strict responders at week 13 | 57.7 Percentage of Participants |
| 1PBS1Gel-200 | Outcome Measures in Rheumatology Artthritis Clinical Trials (OMERACT) - and the Osteoarthritis Research Society International (OARSI) Response | Participants who met responders at week 13 | 77.5 Percentage of Participants |