Osteoarthritis of the Knee
Conditions
Brief summary
The purpose of this study is to determine if a single intra-articular injection of Gel-200 is superior to a single injection of Phosphate Buffered Saline (PBS) in subjects with symptomatic osteoarthritis of the knee.
Interventions
DEVICEGel-200
Single intra-articular injection
DEVICEPlacebo
Single intra-articular injection
Sponsors
Seikagaku Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with a diagnosis of painful, symptomatic tibio-femoral osteoarthritis of the knee (Grade 1-3 on Kellgren - Lawrence (K-L) score).
Exclusion criteria
* Subjects with Grade 4 on K-L score * Subjects with inflammatory diseases of the knee other than osteoarthritis such as rheumatoid arthritis * Serious systemic diseases * Female subjects who are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change 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. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change 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. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo. |
| Change From Baseline in WOMAC VAS Total Score | Baseline and Week 13 | Mean of all WOMAC pain, stiffness and physical function subscores on Visual Analog Scale (VAS) of 100 mm; 0 mm meaning no pain, stiffness and difficulty; 100 mm meaning extreme pain, stiffness and difficulty. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo. |
| Outcome Measures in Rheumatology Arthritis Clinical Trials (OMERACT)- and the Osteoarthritis Research Society International (OARSI) Response | Weeks 6 to 13 | Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) strict responses defined by changes 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). |
| Change 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. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo. |
| Change 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. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo. |
| Change From Baseline in Physician Global Evaluations | Baseline and Week 13 | Observed physician global 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. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo. |
| Acetaminophen Consumption | Weeks 9 to 13 (5 weeks) | Weekly mean acetaminophen consumption between weeks 9 and 13. |
| Change From Baseline in Short Form - 36 (SF-36) | Baseline and Week 13 | Scored on physical component scale from 0 (negative health) to 100 (positive health). Calculated norm based with a mean of 50 and a standard deviation of 10. |
Countries
United States
Participant flow
Pre-assignment details
A total of 598 patients were screened.
Participants by arm
| Arm | Count |
|---|---|
| Gel-200 Patients received 1 single dose of Gel-200 (3mL) intra-articular injection into knee joint. | 247 |
| PBS Placebo Patients received 1 single dose of Phosphate Buffered Saline (PBS) placebo (3mL) intra-articular injection into knee joint. | 128 |
| Total | 375 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Others | 7 | 0 |
| Overall Study | Other Treatment Required | 6 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | PBS Placebo | Total | Gel-200 |
|---|---|---|---|
| Age Continuous | 60.3 years STANDARD_DEVIATION 9.97 | 60.7 years STANDARD_DEVIATION 10.14 | 60.9 years STANDARD_DEVIATION 10.24 |
| Body Mass Index (BMI) | 28.7 kilograms/meters square STANDARD_DEVIATION 3.83 | 28.5 kilograms/meters square STANDARD_DEVIATION 4.04 | 28.3 kilograms/meters square STANDARD_DEVIATION 4.14 |
| Physician Global Evaluations | 64.2 scores on a scale STANDARD_DEVIATION 14.25 | 62.4 scores on a scale STANDARD_DEVIATION 14.65 | 61.5 scores on a scale STANDARD_DEVIATION 14.79 |
| Region of Enrollment United States | 128 participants | 375 participants | 247 participants |
| Sex: Female, Male Female | 77 Participants | 224 Participants | 147 Participants |
| Sex: Female, Male Male | 51 Participants | 151 Participants | 100 Participants |
| Subject Global Evaluations | 66.5 scores on a scale STANDARD_DEVIATION 21.21 | 65.3 scores on a scale STANDARD_DEVIATION 21.61 | 64.7 scores on a scale STANDARD_DEVIATION 21.83 |
| WOMAC VAS Pain Subscore | 68.0 scores on a scale STANDARD_DEVIATION 13.05 | 69.8 scores on a scale STANDARD_DEVIATION 14.01 | 70.7 scores on a scale STANDARD_DEVIATION 14.42 |
| WOMAC VAS Physical Function Subcore | 67.6 scores on a scale STANDARD_DEVIATION 15.8 | 68.5 scores on a scale STANDARD_DEVIATION 16.87 | 68.9 scores on a scale STANDARD_DEVIATION 17.41 |
| WOMAC VAS Stiffness Subscore | 69.3 scores on a scale STANDARD_DEVIATION 17.31 | 70.8 scores on a scale STANDARD_DEVIATION 17.43 | 71.6 scores on a scale STANDARD_DEVIATION 17.48 |
| WOMAC VAS Total Score | 67.8 scores on a scale STANDARD_DEVIATION 14.68 | 68.9 scores on a scale STANDARD_DEVIATION 15.56 | 69.5 scores on a scale STANDARD_DEVIATION 15.99 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 122 / 249 | 55 / 128 |
| serious Total, serious adverse events | 8 / 249 | 0 / 128 |
Outcome results
Primary
Change 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. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 2 patients with Gel-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 |
|---|---|---|---|
| Gel-200 | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Visual Analog Scale (VAS) Pain Subscore | 27.8 scores on a scale | Standard Deviation 29.26 |
| PBS Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Visual Analog Scale (VAS) Pain Subscore | 22.6 scores on a scale | Standard Deviation 29.31 |
p-value: 0.037Quadratic Spline Model
Secondary
Acetaminophen Consumption
Weekly mean acetaminophen consumption between weeks 9 and 13.
Time frame: Weeks 9 to 13 (5 weeks)
Population: ITT population was used for analysis. 2 patients with Gel-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 |
|---|---|---|---|
| Gel-200 | Acetaminophen Consumption | 2007 milligrams | Standard Deviation 3687 |
| PBS Placebo | Acetaminophen Consumption | 2599 milligrams | Standard Deviation 3806 |
p-value: 0.041Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Physician Global Evaluations
Observed physician global 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. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 2 patients with Gel-200 were removed from ITT population analysis and baseline because of no post treatment data according to a pre-specified rule.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gel-200 | Change From Baseline in Physician Global Evaluations | 21.3 scores on a scale | Standard Deviation 28.46 |
| PBS Placebo | Change From Baseline in Physician Global Evaluations | 19.0 scores on a scale | Standard Deviation 26.97 |
p-value: 0.166Quadratic Spline Model
Secondary
Change From Baseline in Short Form - 36 (SF-36)
Scored on physical component scale from 0 (negative health) to 100 (positive health). Calculated norm based with a mean of 50 and a standard deviation of 10.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 2 patients with Gel-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 |
|---|---|---|---|
| Gel-200 | Change From Baseline in Short Form - 36 (SF-36) | 4.6 scores | Standard Deviation 9.34 |
| PBS Placebo | Change From Baseline in Short Form - 36 (SF-36) | 5.3 scores | Standard Deviation 9.04 |
p-value: >0.05Wilcoxon (Mann-Whitney)
Secondary
Change 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. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 2 patients with Gel-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 |
|---|---|---|---|
| Gel-200 | Change From Baseline in Subject Global Evaluations | 22.8 scores on a scale | Standard Deviation 33.08 |
| PBS Placebo | Change From Baseline in Subject Global Evaluations | 22.0 scores on a scale | Standard Deviation 30.58 |
p-value: 0.746Quadratic Spline Model
Secondary
Change 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. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 2 patients with Gel-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 |
|---|---|---|---|
| Gel-200 | Change From Baseline in WOMAC VAS Physical Function Subscore | 26.2 scores on a scale | Standard Deviation 28.81 |
| PBS Placebo | Change From Baseline in WOMAC VAS Physical Function Subscore | 21.0 scores on a scale | Standard Deviation 28.62 |
p-value: 0.071Quadratic Spline Model
Secondary
Change 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. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 2 patients with Gel-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 |
|---|---|---|---|
| Gel-200 | Change From Baseline in WOMAC VAS Stiffness Subscore | 26.9 scores on a scale | Standard Deviation 30.46 |
| PBS Placebo | Change From Baseline in WOMAC VAS Stiffness Subscore | 22.5 scores on a scale | Standard Deviation 28.66 |
p-value: 0.122Quadratic Spline Model
Secondary
Change From Baseline in WOMAC VAS Total Score
Mean of all WOMAC pain, stiffness and physical function subscores on Visual Analog Scale (VAS) of 100 mm; 0 mm meaning no pain, stiffness and difficulty; 100 mm meaning extreme pain, stiffness and difficulty. Change in score from baseline to week 13 was calculated as baseline minus week 13. Primary endpoint was the model estimated difference between Gel-200 and PBS placebo.
Time frame: Baseline and Week 13
Population: ITT population was used for analysis. 2 patients with Gel-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 |
|---|---|---|---|
| Gel-200 | Change From Baseline in WOMAC VAS Total Score | 26.6 scores on a scale | Standard Deviation 28.41 |
| PBS Placebo | Change From Baseline in WOMAC VAS Total Score | 21.5 scores on a scale | Standard Deviation 28.37 |
p-value: 0.058Quadratic Spline Model
Secondary
Outcome Measures in Rheumatology Arthritis 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 changes 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 6 to 13
Population: ITT population was used for analysis. 2 patients with Gel-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) |
|---|---|---|---|
| Gel-200 | Outcome Measures in Rheumatology Arthritis Clinical Trials (OMERACT)- and the Osteoarthritis Research Society International (OARSI) Response | Participants who met strict responders at Week 13 | 45.9 Percentage |
| Gel-200 | Outcome Measures in Rheumatology Arthritis Clinical Trials (OMERACT)- and the Osteoarthritis Research Society International (OARSI) Response | Participants who met responders at Week 13 | 61.0 Percentage |
| PBS Placebo | Outcome Measures in Rheumatology Arthritis Clinical Trials (OMERACT)- and the Osteoarthritis Research Society International (OARSI) Response | Participants who met strict responders at Week 13 | 38.7 Percentage |
| PBS Placebo | Outcome Measures in Rheumatology Arthritis Clinical Trials (OMERACT)- and the Osteoarthritis Research Society International (OARSI) Response | Participants who met responders at Week 13 | 54.6 Percentage |
p-value: 0.022Generalized Estimating Equation Model
p-value: 0.242Generalized Estimating Equation Model