SI-613 Study for Knee Osteoarthritis
Sponsor
Seikagaku Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT03209362
Collaborator
Chiltern International Inc. (Industry)
80
10
2
12.8
8
0.6
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
80 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Repeated Intra-Articular Injection of SI-613 in Patients With Osteoarthritis of the Knee
Actual Study Start Date
:
Oct 19, 2017
Actual Primary Completion Date
:
Aug 17, 2018
Actual Study Completion Date
:
Nov 13, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SI-613
|
Combination Product: SI-613
SI-613 will be repeated intra-articularly administered.
|
| Placebo Comparator: Placebo
|
Combination Product: Placebo
Placebo will be repeated intra-articularly administered.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tucson Orthopaedic Institute | Tucson | Arizona | United States | 85712 |
| 2 | MM Medical Center, Inc. | Miami | Florida | United States | 33185 |
| 3 | Quality Research and Medical Center, LLC | Miami | Florida | United States | 33186 |
| 4 | Heartland Research Associates, LLC | Newton | Kansas | United States | 67114 |
| 5 | Central Kentucky Research Associates | Lexington | Kentucky | United States | 40509 |
| 6 | Sundance Clinical Research, LLC | Saint Louis | Missouri | United States | 63141 |
| 7 | Rochester Clinical Research | Rochester | New York | United States | 14609 |
| 8 | Upstate Clinical Research Associates, LLC | Williamsville | New York | United States | 14221 |
| 9 | New Horizons Clinical Research | Cincinnati | Ohio | United States | 45242 |
| 10 | Altoona Center for Clinical Research | Duncansville | Pennsylvania | United States | 16635 |
Sponsors and Collaborators
- Seikagaku Corporation
- Chiltern International Inc.
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Seikagaku Corporation
ClinicalTrials.gov Identifier:
NCT03209362
Other Study ID Numbers:
- 613 /1121
First Posted:
Jul 6, 2017
Last Update Posted:
Nov 4, 2021
Last Verified:
Nov 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Seikagaku Corporation
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | SI-613 | Placebo |
|---|---|---|
| Arm/Group Description | The participants received repeated intra-articular knee injection of 30 mg SI-613 (1 injection every 4 weeks, total of 3 injections). | The participants received repeated intra-articular knee injection of Placebo (1 injection every 4 weeks, total of 3 injections). |
| Period Title: Overall Study | ||
| STARTED | 39 | 41 |
| COMPLETED | 37 | 38 |
| NOT COMPLETED | 2 | 3 |
Baseline Characteristics
| Arm/Group Title | SI-613 | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | The participants received repeated intra-articular knee injection of 30 mg SI-613 (1 injection every 4 weeks, total of 3 injections). | The participants received repeated intra-articular knee injection of Placebo (1 injection every 4 weeks, total of 3 injections). | Total of all reporting groups |
| Overall Participants | 39 | 41 | 80 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
59.5
(7.32)
|
59.4
(8.32)
|
59.4
(7.80)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
19
48.7%
|
22
53.7%
|
41
51.3%
|
| Male |
20
51.3%
|
19
46.3%
|
39
48.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
14
35.9%
|
15
36.6%
|
29
36.3%
|
| Not Hispanic or Latino |
25
64.1%
|
26
63.4%
|
51
63.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
1
2.6%
|
1
2.4%
|
2
2.5%
|
| Asian |
1
2.6%
|
0
0%
|
1
1.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
7.7%
|
7
17.1%
|
10
12.5%
|
| White |
34
87.2%
|
33
80.5%
|
67
83.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Body Mass Index (BMI) (Kilograms / meter square) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Kilograms / meter square] |
30.62
(4.251)
|
30.64
(4.669)
|
30.63
(4.442)
|
Outcome Measures
| Title | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore Over 12 Weeks |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | SI-613 | Placebo |
|---|---|---|
| Arm/Group Description | The participants received repeated intra-articular knee injection of 30 mg SI-613 (1 injection every 4 weeks, total of 3 injections). | The participants received repeated intra-articular knee injection of Placebo (1 injection every 4 weeks, total of 3 injections). |
| Measure Participants | 39 | 41 |
| Least Squares Mean (95% Confidence Interval) [score on a scale] |
-29.9
|
-27.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SI-613, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5453 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -2.9 | |
| Confidence Interval |
(2-Sided) 95% -12.4 to 6.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in WOMAC Pain Subscore at Weeks 12 and 26 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | SI-613 | Placebo |
|---|---|---|
| Arm/Group Description | The participants received repeated intra-articular knee injection of 30 mg SI-613 (1 injection every 4 weeks, total of 3 injections). | The participants received repeated intra-articular knee injection of Placebo (1 injection every 4 weeks, total of 3 injections). |
| Measure Participants | 39 | 41 |
| Change at Week 12 |
-40.4
|
-36.9
|
| Change at Week 26 |
-41.7
|
-38.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SI-613, Placebo |
|---|---|---|
| Comments | Week 12 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5386 |
| Comments | ||
| Method | Longitudinal model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -3.5 | |
| Confidence Interval |
(2-Sided) 95% -14.9 to 7.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SI-613, Placebo |
|---|---|---|
| Comments | Week 26 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5873 |
| Comments | ||
| Method | Longitudinal model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -3.3 | |
| Confidence Interval |
(2-Sided) 95% -15.2 to 8.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in WOMAC Physical Function Subscore at Weeks 12 and 26 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | SI-613 | Placebo |
|---|---|---|
| Arm/Group Description | The participants received repeated intra-articular knee injection of 30 mg SI-613 (1 injection every 4 weeks, total of 3 injections). | The participants received repeated intra-articular knee injection of Placebo (1 injection every 4 weeks, total of 3 injections). |
| Measure Participants | 39 | 41 |
| Change at Week 12 |
-39.2
|
-36.3
|
| Change at Week 26 |
-38.5
|
-36.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SI-613, Placebo |
|---|---|---|
| Comments | Week 12 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6347 |
| Comments | ||
| Method | Longitudinal model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -2.9 | |
| Confidence Interval |
(2-Sided) 95% -15.0 to 9.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SI-613, Placebo |
|---|---|---|
| Comments | Week 26 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7806 |
| Comments | ||
| Method | Longitudinal model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -14.3 to 10.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in WOMAC Stiffness Subscore at Weeks 12 and 26 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | SI-613 | Placebo |
|---|---|---|
| Arm/Group Description | The participants received repeated intra-articular knee injection of 30 mg SI-613 (1 injection every 4 weeks, total of 3 injections). | The participants received repeated intra-articular knee injection of Placebo (1 injection every 4 weeks, total of 3 injections). |
| Measure Participants | 39 | 41 |
| Change at Week 12 |
-38.2
|
-37.3
|
| Change at Week 26 |
-41.4
|
-35.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SI-613, Placebo |
|---|---|---|
| Comments | Week 12 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8819 |
| Comments | ||
| Method | Longitudinal model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -0.9 | |
| Confidence Interval |
(2-Sided) 95% -13.2 to 11.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SI-613, Placebo |
|---|---|---|
| Comments | Week 26 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3796 |
| Comments | ||
| Method | Longitudinal model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -5.6 | |
| Confidence Interval |
(2-Sided) 95% -18.3 to 7.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in WOMAC Total Score at Weeks 12 and 26 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | SI-613 | Placebo |
|---|---|---|
| Arm/Group Description | The participants received repeated intra-articular knee injection of 30 mg SI-613 (1 injection every 4 weeks, total of 3 injections). | The participants received repeated intra-articular knee injection of Placebo (1 injection every 4 weeks, total of 3 injections). |
| Measure Participants | 39 | 41 |
| Change at Week 12 |
-39.4
|
-36.4
|
| Change at Week 26 |
-39.4
|
-36.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SI-613, Placebo |
|---|---|---|
| Comments | Week 12 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6217 |
| Comments | ||
| Method | Longitudinal model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -3.0 | |
| Confidence Interval |
(2-Sided) 95% -14.9 to 9.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SI-613, Placebo |
|---|---|---|
| Comments | Week 26 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6901 |
| Comments | ||
| Method | Longitudinal model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference |
| Estimated Value | -2.5 | |
| Confidence Interval |
(2-Sided) 95% -14.8 to 9.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Baseline up to Week 26 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | SI-613 | Placebo | ||
| Arm/Group Description | The participants received repeated intra-articular knee injection of 30 mg SI-613 (1 injection every 4 weeks, total of 3 injections). | The participants received repeated intra-articular knee injection of Placebo (1 injection every 4 weeks, total of 3 injections). | ||
All Cause Mortality |
||||
| SI-613 | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/39 (0%) | 0/41 (0%) | ||
Serious Adverse Events |
||||
| SI-613 | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/39 (2.6%) | 1/41 (2.4%) | ||
| Injury, poisoning and procedural complications | ||||
| Heat exhaustion | 1/39 (2.6%) | 0/41 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Plasma cell myeloma | 0/39 (0%) | 1/41 (2.4%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pneumonitis | 1/39 (2.6%) | 0/41 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| SI-613 | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/39 (17.9%) | 3/41 (7.3%) | ||
| General disorders | ||||
| Injection site joint pain | 3/39 (7.7%) | 2/41 (4.9%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 5/39 (12.8%) | 2/41 (4.9%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Clinical Development Dept. |
|---|---|
| Organization | Seikagaku Corporation |
| Phone | (81)3-5220-8948 |
| taku.hosaka@seikagaku.co.jp |
Responsible Party:
Seikagaku Corporation
ClinicalTrials.gov Identifier:
NCT03209362
Other Study ID Numbers:
- 613 /1121
First Posted:
Jul 6, 2017
Last Update Posted:
Nov 4, 2021
Last Verified:
Nov 1, 2021