A Study Evaluating the Safety and Efficacy of SM04690 for... | NCT03122860 | Trialant
NCT03122860
Sponsor
Biosplice Therapeutics, Inc.
Status
Completed
Last Update Posted
Jun 11, 2021Actual
Enrollment
700Actual
Phase
Phase 2
Conditions
Knee Osteoarthritis
Interventions
SM04690
Placebo
Sham
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT03122860
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
SM04690-OA-04
Secondary IDs
Not provided
Brief Title
A Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
Official Title
A Phase 2, 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis
Acronym
Not provided
Organization
Biosplice Therapeutics, Inc.INDUSTRY
Status Module
Record Verification Date
May 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Apr 24, 2017Actual
Primary Completion Date
Apr 30, 2018Actual
Completion Date
Apr 30, 2018Actual
First Submitted Date
Apr 18, 2017
First Submission Date that Met QC Criteria
Apr 20, 2017
First Posted Date
Apr 21, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Mar 19, 2021
Results First Submitted that Met QC Criteria
Apr 26, 2021
Results First Posted Date
May 18, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
May 10, 2019
Certification/Extension First Submitted that Passed QC Review
Apr 26, 2021
Certification/Extension First Posted Date
May 18, 2021Actual
Last Update Submitted Date
May 20, 2021
Last Update Posted Date
Jun 11, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Biosplice Therapeutics, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This phase 2 study is a placebo-controlled, double-blind, parallel group study of four concentrations of SM04690 (0.03, 0.07, 0.15, and 0.23 mg per 2 mL injection) injected intraarticularly (IA) into the target knee joint of subjects with moderately to severely symptomatic osteoarthritis (OA). Based on previous studies of SM04690, key phenotypes of laterality (unilateral vs bilateral) as well as chronic pain (as measured by the Widespread Pain Index) were identified as confounding variables impacting the overall assessment of both radiologic and clinical efficacy outcomes. The design of SM04690-OA-04 is based upon previous study designs while assessing strategies to combat the confounding impact of laterality and chronic pain. To evaluate the effect of IA vehicle injection on patient-reported outcomes (PRO) such as pain, stiffness, and function in OA, this study also includes one cohort that receives a 2 mL IA injection of vehicle (placebo), and one cohort that receives a sham injection (i.e., a needle stick with 0 mL vehicle injected).
Detailed Description
Not provided
Conditions Module
Conditions
Knee Osteoarthritis
Keywords
SM04690
Wnt pathway inhibitor
osteoarthritis
Samumed
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
700Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
0.03 mg SM04690
Experimental
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
Drug: SM04690
0.07 mg SM04690
Experimental
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
Drug: SM04690
0.15 mg SM04690
Experimental
Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
Drug: SM04690
0.23 mg SM04690
Experimental
Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle
Drug: SM04690
Placebo
Placebo Comparator
Single intra-articular injection of 0 mg SM04690 in 2 mL vehicle
Other: Placebo
Sham
Sham Comparator
Single intra-articular injection of 0 mg SM04690 in 0 mL vehicle
Interventions
Name
Type
Description
Arm Group Labels
Other Names
SM04690
Drug
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study
0.03 mg SM04690
0.07 mg SM04690
0.15 mg SM04690
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS)
Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 24. The pain NRS is an 11-point scale [0-10] for subject self-reporting of average knee pain in the last 24 hours; 0 indicates no pain, and 10 represents the worst possible pain (pain as bad as one can imagine).
Baseline and Week 24
Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain)
Change from baseline OA pain in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 24. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Pain subscore is standardized and reported ranging from 0 to 100 [0 = no pain; 100 = pain as bad as it can be].
Baseline and Week 24
Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)
Change from baseline OA function in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function) at Week 24. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore is standardized and reported ranging from 0 to 100 [0 = no functional disability, 100 = unable to function].
Baseline and Week 24
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)
Change From Baseline OA Pain in the Target Knee as Assessed by WOMAC Pain Subscore (WOMAC Pain)
Change from baseline OA pain in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 12. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Pain subscore is standardized and reported ranging from 0 to 100 [0 = no pain, 100 = pain as bad as it can be].
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Ambulatory
Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at screening (clinical AND radiographic criteria); OA of the knee is not to be secondary to any rheumatologic conditions (e.g., rheumatoid arthritis)
Pain compatible with OA of the knee(s) for at least 26 weeks prior to screening
Primary source of pain throughout the body is due to OA in the target knee
Willingness to use an electronic diary on a daily basis in the evening for the screening period and 24-week study duration
Negative drug test for opioids and drugs of abuse, except alcohol and marijuana, at screening
Subjects with depression or anxiety must be clinically stable for 12 weeks prior to screening, and, if on treatment for depression or anxiety, be on 12 weeks of stable therapy
Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
Subjects must have read and understood the informed consent form, and must have signed it prior to any study-related procedure being performed
Exclusion Criteria:
Women who are pregnant, lactating, or have a positive pregnancy result at screening
Women of child bearing potential who are sexually active and are not willing to use a highly effective method of birth control during the study period
Males who are sexually active and have a partner who is capable of becoming pregnant, neither of whom have had surgery to become sterilized or whom are not using a highly effective method of birth control
Body mass index (BMI) > 35
Partial or complete joint replacement in either knee
Currently requires regular use of ambulatory assistive devices (e.g., wheelchair, parallel bars, walker, canes, or crutches) or use of a lower extremity prosthesis, and/or a structural knee brace
Previous participation in a Samumed clinical trial investigating SM04690
Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to screening
Any planned surgery during the study period
History of malignancy within the last 5 years; however, subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible if completely excised. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years prior to any study injection
Comorbid conditions that could affect study endpoint assessments of the target knee, including, but not limited to, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, gout or pseudogout, and fibromyalgia
Any diagnosed psychiatric condition that includes, but is not limited to, a history of mania, bipolar disorder, psychotic disorder, schizophrenia, schizoaffective disorder, major depressive disorder, or generalized anxiety disorder
Participation in a clinical research trial that included the receipt of an investigational product or any experimental therapeutic procedure, or an observational research trial related to osteoarthritis within 8 weeks prior to any study injection, or planned participation in any such trial
Treatment of the target knee with intra-articular glucocorticoids (e.g., methylprednisolone) within 12 weeks prior to screening
Any intra-articular injection into the target knee with a therapeutic aim including, but not limited to, viscosupplementation (e.g., hyaluronic acid), platelet-rich plasma (PRP), and stem cell therapies within 24 weeks prior to screening; treatment of the target knee with intra-articular glucocorticoids greater than 12 weeks prior to screening is allowed
Treatment with systemic glucocorticoids greater than 10 mg prednisone or the equivalent per day within 4 weeks prior to screening
Effusion of the target knee clinically requiring aspiration within 12 weeks prior to screening
Use of electrotherapy, acupuncture, and/or chiropractic treatments for knee OA within 4 weeks prior to screening
Any known active infections, including urinary tract infection, upper respiratory tract infection, sinusitis, suspicion of intra-articular infection, hepatitis B or hepatitis C infection, and/or infections that may compromise the immune system such as human immunodeficiency virus (HIV) at study start
Use of centrally acting analgesics (e.g., duloxetine) within 12 weeks prior to screening
Use of anticonvulsants within 12 weeks prior to screening, unless used for seizure or migraine prophylaxis
Subjects requiring the usage of opioids >1x per week within 12 weeks prior to screening
Use of topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch) for the treatment of knee OA within 7 days of screening
Yazici Y, McAlindon TE, Gibofsky A, Lane NE, Lattermann C, Skrepnik N, Swearingen CJ, Simsek I, Ghandehari H, DiFrancesco A, Gibbs J, Tambiah JRS, Hochberg MC. A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis. Osteoarthritis Cartilage. 2021 May;29(5):654-666. doi: 10.1016/j.joca.2021.02.004. Epub 2021 Feb 12.
The Safety Analysis Set (SAS) [see 'Adverse Events' section] includes all subjects who received a study injection, analyzed as treated. Discrepancy in subject counts between FAS and SAS is the result of subjects who received a treatment that is different from the planned treatment group as randomized. Subjects who received a study treatment not as prescribed in the pharmacy manual are summarized in the "Other" treatment group for safety analysis reporting.
Recruitment Details
The Full Analysis Set (FAS) includes all subjects who were randomized and received a study injection, analyzed as randomized.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
FG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
2
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Apr 23, 2018
Mar 19, 2021
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Triple
Masking Description
Not provided
Who Masked
ParticipantInvestigatorOutcomes Assessor
Other: Sham
0.23 mg SM04690
Placebo
Other
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study
Placebo
Sham
Other
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study
Sham
Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee
Change from baseline in mJSW as documented by radiograph of the target knee.
Baseline and Week 24
Baseline and Week 24
Baseline and Week 12
Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)
Change from baseline OA function in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function) at Week 12. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore is standardized and reported ranging from 0 to 100 [0 = no functional disability, 100 = unable to function].
Baseline and Week 12
Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS
Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 12. The pain NRS is an 11-point scale [0-10] for subject self-reporting of average knee pain in the last 24 hours; 0 indicates no pain, and 10 represents the worst possible pain (pain as bad as one can imagine).
Baseline and Week 12
Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)
Tambiah J, Kennedy S, Swearingen C, McAlindon T, Yazici Y. Impact of structural severity on outcomes in knee osteoarthritis: an analysis of data from phase 2 and phase 3 lorecivivint clinical trials. Rheumatology (Oxford). 2025 May 1;64(5):2583-2590. doi: 10.1093/rheumatology/keae610.
Tambiah JRS, Simsek I, Swearingen CJ, Kennedy S, Cole BJ, McAlindon TE, Yazici Y. Comparing Patient-Reported Outcomes From Sham and Saline-Based Placebo Injections for Knee Osteoarthritis: Data From a Randomized Clinical Trial of Lorecivivint. Am J Sports Med. 2022 Mar;50(3):630-636. doi: 10.1177/03635465211067201. Epub 2022 Jan 10.
Tambiah JRS, Kennedy S, Swearingen CJ, Simsek I, Yazici Y, Farr J, Conaghan PG. Individual Participant Symptom Responses to Intra-Articular Lorecivivint in Knee Osteoarthritis: Post Hoc Analysis of a Phase 2B Trial. Rheumatol Ther. 2021 Jun;8(2):973-985. doi: 10.1007/s40744-021-00316-w. Epub 2021 Jun 8.
FG002
0.15 mg SM04690
Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
FG003
0.23 mg SM04690
Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle
FG004
Placebo
Single intra-articular injection of 0 mg SM04690 in 2 mL vehicle
FG005
Sham
Single intra-articular injection of 0 mg SM04690 in 0 mL vehicle
FG000117 subjects
FG001116 subjects
FG002117 subjects
FG003116 subjects
FG004117 subjects
FG005117 subjects
Full Analysis Set
FG000116 subjects
FG001115 subjects
FG002115 subjects
FG003116 subjects
FG004116 subjects
FG005117 subjects
COMPLETED
FG000107 subjects
FG001111 subjects
FG002105 subjects
FG003105 subjects
FG004102 subjects
FG005105 subjects
NOT COMPLETED
FG00010 subjects
FG0015 subjects
FG00212 subjects
FG00311 subjects
FG00415 subjects
FG00512 subjects
Type
Comment
Reasons
Discontinued Before Treatment
FG0001 subjects
FG0011 subjects
FG0022 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Adverse Event
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
FG004
Lost to Follow-up
FG0005 subjects
FG0012 subjects
FG0023 subjects
FG0033 subjects
FG004
Subject Non-Compliance
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0003 subjects
FG0012 subjects
FG0025 subjects
FG0037 subjects
FG004
All subjects who were randomized and received a study injection, analyzed as randomized (Full Analysis Set [FAS]). FAS is used to describe the analysis set which is as complete as possible and as close as possible to the intent-to-treat ideal of including all randomized subjects.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
BG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
BG002
0.15 mg SM04690
Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
BG003
0.23 mg SM04690
Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle
BG004
Placebo
Single intra-articular injection of 0 mg SM04690 in 2 mL vehicle
BG005
Sham
Single intra-articular injection of 0 mg SM04690 in 0 mL vehicle
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000116
BG001115
BG002115
BG003116
BG004116
BG005117
BG006695
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG000116
ParticipantsBG001115
ParticipantsBG002115
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000116
ParticipantsBG001115
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000116
ParticipantsBG001115
ParticipantsBG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000116
ParticipantsBG001115
ParticipantsBG002
Body Mass Index (BMI)
BMI was not collected for one participant in the 0.03 mg SM04690 cohort.
Mean
Standard Deviation
kg/m²
Title
Denominators
Categories
ParticipantsBG000115
ParticipantsBG001115
ParticipantsBG002
Kellgren-Lawrence Grade
Participants' knee osteoarthritis was graded in accordance with the following definitions of Kellgren-Lawrence Grade: None (Grade 0) - Normal appearance of the knee; Doubtful (Grade 1): Doubtful narrowing of joint space and possible osteophytic lipping; Minimal (Grade 2): Definite osteophytes and possible narrowing of joint space; Moderate (Grade 3): Moderate multiple osteophytes, definite narrowing of the joint space, some sclerosis and possible deformity of bone ends; Severe (Grade 4): Large osteophytes, marked narrowing of joint space, severe sclerosis and definite deformity of bone ends.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000116
ParticipantsBG001
Osteoarthritis Laterality
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000116
ParticipantsBG001115
ParticipantsBG002
Widespread Pain (WP)
Subjects were required to complete the Widespread Pain Index & Symptom Severity questionnaire. The Widespread Pain Index (WPI) is a body map consisting of 19 prespecified areas where subjects can indicate the presence of pain during the past seven days with a possible score 0-19. Question 2 of the Symptom Severity section of the questionnaire (SSQ2) focuses on the presence and severity of three prespecified symptoms (fatigue, trouble thinking or remembering, and waking up tired) during the past seven days with a possible score of 0-9. WP+: WPI > 4 and/or SSQ2 > 2, WP-: WPI <= 4 and SSQ2 <= 2
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000116
ParticipantsBG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS)
Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 24. The pain NRS is an 11-point scale [0-10] for subject self-reporting of average knee pain in the last 24 hours; 0 indicates no pain, and 10 represents the worst possible pain (pain as bad as one can imagine).
Data is reported as observed with no imputation. Discrepancy between the number of participants analyzed and the number of participants assigned to the arms is the result of missing data and/or subject withdrawal.
Posted
Mean
Standard Deviation
score on a scale
Baseline and Week 24
ID
Title
Description
OG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
OG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
OG002
0.15 mg SM04690
Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
OG003
0.23 mg SM04690
Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle
OG004
Placebo
Single intra-articular injection of 0 mg SM04690 in 2 mL vehicle
OG005
Sham
Single intra-articular injection of 0 mg SM04690 in 0 mL vehicle
Units
Counts
Participants
OG00098
OG001102
OG00292
OG003
Title
Denominators
Categories
Title
Measurements
OG000-2.77± 2.44
OG001-2.93± 2.21
OG002-2.43± 2.18
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
ANCOVA
0.179
Median Difference (Final Values)
-0.46
2-Sided
95
-1.13
0.21
Superiority
OG001
OG004
ANCOVA
0.031
Primary
Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain)
Change from baseline OA pain in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 24. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Pain subscore is standardized and reported ranging from 0 to 100 [0 = no pain; 100 = pain as bad as it can be].
Data is reported as observed with no imputation. Discrepancy between the number of participants analyzed and the number of participants assigned to the arms is the result of missing data and/or subject withdrawal.
Posted
Mean
Standard Error
score on a scale
Baseline and Week 24
ID
Title
Description
OG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
OG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
OG002
Primary
Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)
Change from baseline OA function in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function) at Week 24. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore is standardized and reported ranging from 0 to 100 [0 = no functional disability, 100 = unable to function].
Data is reported as observed with no imputation. Discrepancy between the number of participants analyzed and the number of participants assigned to the arms is the result of missing data and/or subject withdrawal.
Posted
Mean
Standard Deviation
score on a scale
Baseline and Week 24
ID
Title
Description
OG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
OG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
OG002
Primary
Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee
Change from baseline in mJSW as documented by radiograph of the target knee.
Data is reported as observed with no imputation. Discrepancy between the number of participants analyzed and the number of participants assigned to the arms is the result of missing data and/or subject withdrawal.
Posted
Mean
Standard Deviation
mm
Baseline and Week 24
ID
Title
Description
OG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
OG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
OG002
0.15 mg SM04690
Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
OG003
0.23 mg SM04690
Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle
OG004
Secondary
Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)
Data is reported as observed with no imputation. Discrepancy between the number of participants analyzed and the number of participants assigned to the arms is the result of missing data and/or subject withdrawal.
Posted
Mean
Standard Deviation
mm
Baseline and Week 24
ID
Title
Description
OG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
OG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
OG002
0.15 mg SM04690
Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
Other Pre-specified
Change From Baseline OA Pain in the Target Knee as Assessed by WOMAC Pain Subscore (WOMAC Pain)
Change from baseline OA pain in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) pain subscore (WOMAC Pain) at Week 12. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Pain subscore is standardized and reported ranging from 0 to 100 [0 = no pain, 100 = pain as bad as it can be].
Data is reported as observed with no imputation. Discrepancy between the number of participants analyzed and the number of participants assigned to the arms is the result of missing data and/or subject withdrawal.
Posted
Mean
Standard Deviation
score on a scale
Baseline and Week 12
ID
Title
Description
OG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
OG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
OG002
0.15 mg SM04690
Other Pre-specified
Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function)
Change from baseline OA function in the target knee as assessed by WOMAC Numeric Rating Scale (NRS 3.1) physical functioning subscore (WOMAC Function) at Week 12. The WOMAC is a widely-used, proprietary outcome measurement tool used by health professionals to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 10 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore is standardized and reported ranging from 0 to 100 [0 = no functional disability, 100 = unable to function].
Data is reported as observed with no imputation. Discrepancy between the number of participants analyzed and the number of participants assigned to the arms is the result of missing data and/or subject withdrawal.
Posted
Mean
Standard Deviation
score on a scale
Baseline and Week 12
ID
Title
Description
OG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
OG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
OG002
Other Pre-specified
Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS
Change from baseline OA pain in the target knee as assessed by the weekly average of daily pain NRS at Week 12. The pain NRS is an 11-point scale [0-10] for subject self-reporting of average knee pain in the last 24 hours; 0 indicates no pain, and 10 represents the worst possible pain (pain as bad as one can imagine).
Data is reported as observed with no imputation. Discrepancy between the number of participants analyzed and the number of participants assigned to the arms is the result of missing data and/or subject withdrawal.
Posted
Mean
Standard Deviation
score on a scale
Baseline and Week 12
ID
Title
Description
OG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
OG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
OG002
0.15 mg SM04690
Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
OG003
0.23 mg SM04690
Other Pre-specified
Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)
Data is reported as observed with no imputation. Discrepancy between the number of participants analyzed and the number of participants assigned to the arms is the result of missing data and/or subject withdrawal.
Posted
Mean
Standard Deviation
score on a scale
Baseline and Week 12
ID
Title
Description
OG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
OG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
OG002
0.15 mg SM04690
Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
Time Frame
Data regarding treatment-emergent adverse events (TEAEs) was collected in this study. TEAEs are events that occur during the course of the study that are not present prior to Day 1 study medication injection, or, if present at the time of study medication injection, have worsened in severity during the course of the study. TEAEs were assessed at each study visit from the time of study medication injection on study visit Day 1 through Week 24 (End-of-Study)/Early Termination.
Description
The Safety Analyses Set [SAS] includes all subjects who received a study injection, analyzed as treated. Discrepancy in subject counts between SAS and Full Analysis Set [FAS] is the result of subjects who received a treatment that is different from the planned treatment group as randomized. Subjects who received a study treatment not as prescribed in the pharmacy manual are summarized in the "Other" treatment group for safety analysis reporting.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
0.03 mg SM04690
Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle
0
106
2
106
14
106
EG001
0.07 mg SM04690
Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle
0
104
0
104
19
104
EG002
0.15 mg SM04690
Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle
0
106
0
106
14
106
EG003
0.23 mg SM04690
Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle
0
106
2
106
17
106
EG004
Placebo
Single intra-articular injection of 0 mg SM04690 in 2 mL vehicle
0
114
1
114
15
114
EG005
Sham
Single intra-articular injection of 0 mg SM04690 in 0 mL vehicle
0
120
0
120
22
120
EG006
Other
Single intra-articular injection of an unidentified dose of SM04690 or Placebo due to incorrectly performed dilution or documentation by a pharmacist.
0
39
1
39
9
39
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Coronary artery disease
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected106 at risk
EG0010 events0 affected104 at risk
EG0020 events0 affected106 at risk
EG0030 events0 affected106 at risk
EG0041 events1 affected114 at risk
EG0050 events0 affected120 at risk
EG0060 events0 affected39 at risk
Supraventricular tachycardia
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected106 at risk
EG0010 events0 affected104 at risk
EG0020 events0 affected106 at risk
EG003
Appendicitis perforated
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected106 at risk
EG0010 events0 affected104 at risk
EG0020 events0 affected106 at risk
EG003
Invasive ductal breast carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)