Osteoarthritis, Knee
Conditions
Keywords
Knee, Osteoarthritis, Intra-articular injection
Brief summary
The objective of the study is to evaluate the efficacy and safety of intra-articular injections of SI-613 compared with placebo for knee OA.
Interventions
COMBINATION_PRODUCTSI-613
SI-613 will be repeated intra-articularly administered.
COMBINATION_PRODUCTPlacebo
Placebo will be repeated intra-articularly administered.
Sponsors
Chiltern International Inc.
Seikagaku Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Provides their written informed consent. * Has a diagnosis at the time of screening of OA of the knee according to American College of Rheumatology (ACR) criteria * Is willing to switch to using acetaminophen as a rescue medication
Exclusion criteria
* Has a body mass index (BMI) greater than or equal to 40 kg/m2 at screening. * Secondary OA * Is a female subject who is pregnant or lactating. * Is currently hospitalized or has a planned hospitalization during the life of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore Over 12 Weeks | Baseline over 12 weeks | Observed VAS of 100 mm; 0 mm meaning no pain; 100 mm meaning extreme pain. Change in score from baseline over 12 weeks was analyzed using a repeated measures Analysis of Covariance (ANCOVA) model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in WOMAC Pain Subscore at Weeks 12 and 26 | Baseline, Weeks 12 and 26 | Observed VAS of 100 mm; 0 mm meaning no pain; 100 mm meaning extreme pain. Changes in score from baseline at Weeks 12 and 26 were analyzed using a longitudinal model. |
| Change From Baseline in WOMAC Physical Function Subscore at Weeks 12 and 26 | Baseline, Weeks 12 and 26 | Observed VAS of 100 mm; 0 mm meaning no difficulty; 100 mm meaning extreme difficulty. Changes in score from baseline at Weeks 12 and 26 were analyzed using a longitudinal model. |
| Change From Baseline in WOMAC Stiffness Subscore at Weeks 12 and 26 | Baseline, Weeks 12 and 26 | Observed VAS of 100 mm; 0 mm meaning no stiffness; 100 mm meaning extreme stiffness. Changes in score from baseline at Weeks 12 and 26 were analyzed using a longitudinal model. |
| Change From Baseline in WOMAC Total Score at Weeks 12 and 26 | Baseline, Weeks 12 and 26 | WOMAC total score was the mean of WOMAC pain, physical function and stiffness subscores and ranges from 0 to 100 mm, where higher scores indicated worse response. Changes in WOMAC total score from baseline at Weeks 12 and 26 were analyzed using a longitudinal model. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SI-613 The participants received repeated intra-articular knee injection of 30 mg SI-613 (1 injection every 4 weeks, total of 3 injections). | 39 |
| Placebo The participants received repeated intra-articular knee injection of Placebo (1 injection every 4 weeks, total of 3 injections). | 41 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | SI-613 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 59.5 years STANDARD_DEVIATION 7.32 | 59.4 years STANDARD_DEVIATION 8.32 | 59.4 years STANDARD_DEVIATION 7.8 |
| Body Mass Index (BMI) | 30.62 Kilograms / meter square STANDARD_DEVIATION 4.251 | 30.64 Kilograms / meter square STANDARD_DEVIATION 4.669 | 30.63 Kilograms / meter square STANDARD_DEVIATION 4.442 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 15 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 26 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 7 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 34 Participants | 33 Participants | 67 Participants |
| Sex: Female, Male Female | 19 Participants | 22 Participants | 41 Participants |
| Sex: Female, Male Male | 20 Participants | 19 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 41 |
| other Total, other adverse events | 7 / 39 | 3 / 41 |
| serious Total, serious adverse events | 1 / 39 | 1 / 41 |
Outcome results
Primary
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore Over 12 Weeks
Observed VAS of 100 mm; 0 mm meaning no pain; 100 mm meaning extreme pain. Change in score from baseline over 12 weeks was analyzed using a repeated measures Analysis of Covariance (ANCOVA) model.
Time frame: Baseline over 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| SI-613 | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore Over 12 Weeks | -29.9 score on a scale |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore Over 12 Weeks | -27.0 score on a scale |
p-value: 0.545395% CI: [-12.4, 6.6]ANCOVA
Secondary
Change From Baseline in WOMAC Pain Subscore at Weeks 12 and 26
Observed VAS of 100 mm; 0 mm meaning no pain; 100 mm meaning extreme pain. Changes in score from baseline at Weeks 12 and 26 were analyzed using a longitudinal model.
Time frame: Baseline, Weeks 12 and 26
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| SI-613 | Change From Baseline in WOMAC Pain Subscore at Weeks 12 and 26 | Change at Week 12 | -40.4 score on a scale |
| SI-613 | Change From Baseline in WOMAC Pain Subscore at Weeks 12 and 26 | Change at Week 26 | -41.7 score on a scale |
| Placebo | Change From Baseline in WOMAC Pain Subscore at Weeks 12 and 26 | Change at Week 12 | -36.9 score on a scale |
| Placebo | Change From Baseline in WOMAC Pain Subscore at Weeks 12 and 26 | Change at Week 26 | -38.4 score on a scale |
Comparison: Week 12p-value: 0.538695% CI: [-14.9, 7.8]Longitudinal model
Comparison: Week 26p-value: 0.587395% CI: [-15.2, 8.6]Longitudinal model
Secondary
Change From Baseline in WOMAC Physical Function Subscore at Weeks 12 and 26
Observed VAS of 100 mm; 0 mm meaning no difficulty; 100 mm meaning extreme difficulty. Changes in score from baseline at Weeks 12 and 26 were analyzed using a longitudinal model.
Time frame: Baseline, Weeks 12 and 26
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| SI-613 | Change From Baseline in WOMAC Physical Function Subscore at Weeks 12 and 26 | Change at Week 12 | -39.2 score on a scale |
| SI-613 | Change From Baseline in WOMAC Physical Function Subscore at Weeks 12 and 26 | Change at Week 26 | -38.5 score on a scale |
| Placebo | Change From Baseline in WOMAC Physical Function Subscore at Weeks 12 and 26 | Change at Week 12 | -36.3 score on a scale |
| Placebo | Change From Baseline in WOMAC Physical Function Subscore at Weeks 12 and 26 | Change at Week 26 | -36.7 score on a scale |
Comparison: Week 12p-value: 0.634795% CI: [-15, 9.2]Longitudinal model
Comparison: Week 26p-value: 0.780695% CI: [-14.3, 10.8]Longitudinal model
Secondary
Change From Baseline in WOMAC Stiffness Subscore at Weeks 12 and 26
Observed VAS of 100 mm; 0 mm meaning no stiffness; 100 mm meaning extreme stiffness. Changes in score from baseline at Weeks 12 and 26 were analyzed using a longitudinal model.
Time frame: Baseline, Weeks 12 and 26
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| SI-613 | Change From Baseline in WOMAC Stiffness Subscore at Weeks 12 and 26 | Change at Week 12 | -38.2 score on a scale |
| SI-613 | Change From Baseline in WOMAC Stiffness Subscore at Weeks 12 and 26 | Change at Week 26 | -41.4 score on a scale |
| Placebo | Change From Baseline in WOMAC Stiffness Subscore at Weeks 12 and 26 | Change at Week 12 | -37.3 score on a scale |
| Placebo | Change From Baseline in WOMAC Stiffness Subscore at Weeks 12 and 26 | Change at Week 26 | -35.7 score on a scale |
Comparison: Week 12p-value: 0.881995% CI: [-13.2, 11.4]Longitudinal model
Comparison: Week 26p-value: 0.379695% CI: [-18.3, 7.1]Longitudinal model
Secondary
Change From Baseline in WOMAC Total Score at Weeks 12 and 26
WOMAC total score was the mean of WOMAC pain, physical function and stiffness subscores and ranges from 0 to 100 mm, where higher scores indicated worse response. Changes in WOMAC total score from baseline at Weeks 12 and 26 were analyzed using a longitudinal model.
Time frame: Baseline, Weeks 12 and 26
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| SI-613 | Change From Baseline in WOMAC Total Score at Weeks 12 and 26 | Change at Week 12 | -39.4 score on a scale |
| SI-613 | Change From Baseline in WOMAC Total Score at Weeks 12 and 26 | Change at Week 26 | -39.4 score on a scale |
| Placebo | Change From Baseline in WOMAC Total Score at Weeks 12 and 26 | Change at Week 12 | -36.4 score on a scale |
| Placebo | Change From Baseline in WOMAC Total Score at Weeks 12 and 26 | Change at Week 26 | -36.9 score on a scale |
Comparison: Week 26p-value: 0.690195% CI: [-14.8, 9.8]Longitudinal model
Comparison: Week 12p-value: 0.621795% CI: [-14.9, 9]Longitudinal model