Knee Osteoarthritis
Conditions
Keywords
SM04690, Wnt pathway inhibitor, osteoarthritis, Samumed
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).
Interventions
DRUGSM04690
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study
OTHERPlacebo
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study
OTHERSham
Healthcare professional-administered intra-articular injection performed once on Day 1 of the study
Sponsors
Biosplice Therapeutics, Inc.
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) | Baseline and Week 24 | 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). |
| Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee | Baseline and Week 24 | Change from baseline in mJSW as documented by radiograph of the target knee. |
| Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | Baseline and Week 24 | 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 \[0 = no functional disability, 100 = unable to function\]. |
| Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain) | Baseline and Week 24 | 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 \[0 = no pain; 100 = pain as bad as it can be\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | Baseline and Week 24 | Change from baseline OA disease activity as assessed by PtGA at Week 24. The PtGA was completed using a 100 mm visual analog scale (VAS) adapted from the Patient Assessment Form © 1999, American College of Rheumatology. The subject rated how well he/she was doing, considering all the ways in which illness and health conditions may affected him/her. The VAS scale was anchored by Very Well on the left (scored as 0) and Very Poorly on the right (scored as 100). Higher scores indicated poorer disease assessment by the subject. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline OA Pain in the Target Knee as Assessed by WOMAC Pain Subscore (WOMAC Pain) | Baseline and Week 12 | 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 \[0 = no pain, 100 = pain as bad as it can be\]. |
| Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | Baseline and Week 12 | Change from baseline OA disease activity as assessed by PtGA at Week 12. The PtGA completed using a 100 mm visual analog scale (VAS) adapted from the Patient Assessment Form © 1999, American College of Rheumatology. The subject rated how well he/she was doing, considering all the ways in which illness and health conditions may affected him/her. The VAS scale was anchored by Very Well on the left (scored as 0) and Very Poorly on the right (scored as 100). Higher scores indicated poorer disease assessment by the subject. |
| Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS | Baseline and Week 12 | 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). |
| Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | Baseline and Week 12 | 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 \[0 = no functional disability, 100 = unable to function\]. |
Countries
United States
Participant flow
Recruitment details
The Full Analysis Set (FAS) includes all subjects who were randomized and received a study injection, analyzed as randomized.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 0.03 mg SM04690 Single intra-articular injection of 0.03 mg SM04690 in 2 mL vehicle | 116 |
| 0.07 mg SM04690 Single intra-articular injection of 0.07 mg SM04690 in 2 mL vehicle | 115 |
| 0.15 mg SM04690 Single intra-articular injection of 0.15 mg SM04690 in 2 mL vehicle | 115 |
| 0.23 mg SM04690 Single intra-articular injection of 0.23 mg SM04690 in 2 mL vehicle | 116 |
| Placebo Single intra-articular injection of 0 mg SM04690 in 2 mL vehicle | 116 |
| Sham Single intra-articular injection of 0 mg SM04690 in 0 mL vehicle | 117 |
| Total | 695 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Discontinued Before Treatment | 1 | 1 | 2 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 5 | 2 | 3 | 3 | 5 | 4 |
| Overall Study | Subject Non-Compliance | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 5 | 7 | 9 | 8 |
Baseline characteristics
| Characteristic | Total | 0.03 mg SM04690 | 0.07 mg SM04690 | 0.15 mg SM04690 | 0.23 mg SM04690 | Placebo | Sham |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.0 years STANDARD_DEVIATION 8.5 | 57.9 years STANDARD_DEVIATION 7.9 | 59.9 years STANDARD_DEVIATION 8.6 | 58.4 years STANDARD_DEVIATION 8.3 | 58.5 years STANDARD_DEVIATION 9 | 60.1 years STANDARD_DEVIATION 9 | 59.0 years STANDARD_DEVIATION 8 |
| Body Mass Index (BMI) | 28.97 kg/m² STANDARD_DEVIATION 4.01 | 29.17 kg/m² STANDARD_DEVIATION 3.76 | 29.14 kg/m² STANDARD_DEVIATION 3.64 | 29.38 kg/m² STANDARD_DEVIATION 4.1 | 28.53 kg/m² STANDARD_DEVIATION 4.39 | 28.62 kg/m² STANDARD_DEVIATION 4.29 | 28.97 kg/m² STANDARD_DEVIATION 3.84 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 115 Participants | 21 Participants | 22 Participants | 22 Participants | 10 Participants | 16 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 580 Participants | 95 Participants | 93 Participants | 93 Participants | 106 Participants | 100 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Kellgren-Lawrence Grade Grade 1 | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Kellgren-Lawrence Grade Grade 2 | 291 Participants | 53 Participants | 38 Participants | 47 Participants | 53 Participants | 43 Participants | 57 Participants |
| Kellgren-Lawrence Grade Grade 3 | 398 Participants | 63 Participants | 74 Participants | 68 Participants | 63 Participants | 72 Participants | 58 Participants |
| Kellgren-Lawrence Grade Grade 4 | 5 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Osteoarthritis Laterality Bilateral | 325 Participants | 57 Participants | 53 Participants | 52 Participants | 53 Participants | 55 Participants | 55 Participants |
| Osteoarthritis Laterality Unilateral | 370 Participants | 59 Participants | 62 Participants | 63 Participants | 63 Participants | 61 Participants | 62 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 30 Participants | 5 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 133 Participants | 24 Participants | 22 Participants | 25 Participants | 21 Participants | 17 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 6 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 517 Participants | 85 Participants | 83 Participants | 84 Participants | 89 Participants | 90 Participants | 86 Participants |
| Sex: Female, Male Female | 406 Participants | 76 Participants | 66 Participants | 69 Participants | 61 Participants | 64 Participants | 70 Participants |
| Sex: Female, Male Male | 289 Participants | 40 Participants | 49 Participants | 46 Participants | 55 Participants | 52 Participants | 47 Participants |
| Widespread Pain (WP) WP- | 555 Participants | 92 Participants | 93 Participants | 90 Participants | 93 Participants | 93 Participants | 94 Participants |
| Widespread Pain (WP) WP+ | 140 Participants | 24 Participants | 22 Participants | 25 Participants | 23 Participants | 23 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 106 | 0 / 104 | 0 / 106 | 0 / 106 | 0 / 114 | 0 / 120 | 0 / 39 |
| other Total, other adverse events | 14 / 106 | 19 / 104 | 14 / 106 | 17 / 106 | 15 / 114 | 22 / 120 | 9 / 39 |
| serious Total, serious adverse events | 2 / 106 | 0 / 104 | 0 / 106 | 2 / 106 | 1 / 114 | 0 / 120 | 1 / 39 |
Outcome results
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.
Time frame: Baseline and Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.03 mg SM04690 | Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee | 0.02 mm | Standard Deviation 0.72 |
| 0.07 mg SM04690 | Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee | -0.11 mm | Standard Deviation 0.53 |
| 0.15 mg SM04690 | Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee | -0.11 mm | Standard Deviation 0.92 |
| 0.23 mg SM04690 | Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee | -0.03 mm | Standard Deviation 0.45 |
| Placebo | Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee | -0.01 mm | Standard Deviation 0.6 |
| Sham | Change From Baseline in Medial Joint Space Width (mJSW) of the Target Knee | -0.08 mm | Standard Deviation 0.58 |
p-value: 0.82295% CI: [-0.16, 0.21]ANCOVA
p-value: 0.16295% CI: [-0.27, 0.04]ANCOVA
p-value: 0.26795% CI: [-0.34, 0.09]ANCOVA
p-value: 0.68595% CI: [-0.18, 0.12]ANCOVA
p-value: 0.34295% CI: [-0.09, 0.24]ANCOVA
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 \[0 = no functional disability, 100 = unable to function\].
Time frame: Baseline and Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.03 mg SM04690 | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -27.7 score on a scale | Standard Deviation 21.1 |
| 0.07 mg SM04690 | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -29.3 score on a scale | Standard Deviation 23 |
| 0.15 mg SM04690 | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -23.6 score on a scale | Standard Deviation 21.6 |
| 0.23 mg SM04690 | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -32.4 score on a scale | Standard Deviation 22.1 |
| Placebo | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -24.9 score on a scale | Standard Deviation 23.7 |
| Sham | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -23.8 score on a scale | Standard Deviation 23.7 |
p-value: 0.43295% CI: [-9.04, 3.88]ANCOVA
p-value: 0.1895% CI: [-10.69, 2.02]ANCOVA
p-value: 0.71895% CI: [-5.33, 7.72]ANCOVA
p-value: 0.01795% CI: [-14.54, -1.45]ANCOVA
p-value: 0.68295% CI: [-8.06, 5.29]ANCOVA
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 \[0 = no pain; 100 = pain as bad as it can be\].
Time frame: Baseline and Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.03 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain) | -27.6 score on a scale | Standard Error 22.8 |
| 0.07 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain) | -30.0 score on a scale | Standard Error 22.5 |
| 0.15 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain) | -24.7 score on a scale | Standard Error 21.6 |
| 0.23 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain) | -33.3 score on a scale | Standard Error 22.9 |
| Placebo | Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain) | -25.5 score on a scale | Standard Error 25.8 |
| Sham | Change From Baseline OA Pain in the Target Knee as Assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscore (WOMAC Pain) | -22.5 score on a scale | Standard Error 24.6 |
p-value: 0.22395% CI: [-10.47, 2.46]ANCOVA
p-value: 0.61295% CI: [-8.32, 4.91]ANCOVA
p-value: 0.5995% CI: [-4.89, 8.57]ANCOVA
p-value: 0.03195% CI: [-14.03, -0.69]ANCOVA
p-value: 0.40395% CI: [-9.7, 3.92]ANCOVA
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).
Time frame: Baseline and Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.03 mg SM04690 | Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) | -2.77 score on a scale | Standard Deviation 2.44 |
| 0.07 mg SM04690 | Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) | -2.93 score on a scale | Standard Deviation 2.21 |
| 0.15 mg SM04690 | Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) | -2.43 score on a scale | Standard Deviation 2.18 |
| 0.23 mg SM04690 | Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) | -3.03 score on a scale | Standard Deviation 2.43 |
| Placebo | Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) | -2.26 score on a scale | Standard Deviation 2.44 |
| Sham | Change From Baseline Osteoarthritis (OA) Pain in the Target Knee as Assessed by the Weekly Average of Daily Pain Numeric Rating Scale (NRS) | -2.21 score on a scale | Standard Deviation 2.46 |
p-value: 0.03195% CI: [-1.34, -0.06]ANCOVA
p-value: 0.67595% CI: [-0.81, 0.52]ANCOVA
p-value: 0.02295% CI: [-1.51, -0.12]ANCOVA
p-value: 0.7895% CI: [-0.79, 0.59]ANCOVA
p-value: 0.17995% CI: [-1.13, 0.21]ANCOVA
Secondary
Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)
Change from baseline OA disease activity as assessed by PtGA at Week 24. The PtGA was completed using a 100 mm visual analog scale (VAS) adapted from the Patient Assessment Form © 1999, American College of Rheumatology. The subject rated how well he/she was doing, considering all the ways in which illness and health conditions may affected him/her. The VAS scale was anchored by Very Well on the left (scored as 0) and Very Poorly on the right (scored as 100). Higher scores indicated poorer disease assessment by the subject.
Time frame: Baseline and Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.03 mg SM04690 | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -16.0 mm | Standard Deviation 23.5 |
| 0.07 mg SM04690 | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -19.8 mm | Standard Deviation 27.1 |
| 0.15 mg SM04690 | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -11.9 mm | Standard Deviation 27.5 |
| 0.23 mg SM04690 | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -18.3 mm | Standard Deviation 24.5 |
| Placebo | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -13.0 mm | Standard Deviation 21.6 |
| Sham | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -13.8 mm | Standard Deviation 24.4 |
p-value: 0.595% CI: [-8.36, 4.1]ANCOVA
p-value: 0.08295% CI: [-11.8, 0.72]ANCOVA
p-value: 0.55295% CI: [-8.36, 4.48]ANCOVA
p-value: 0.03395% CI: [-13.16, -0.56]ANCOVA
p-value: 0.88795% CI: [-5.79, 6.68]ANCOVA
Other Pre-specified
Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA)
Change from baseline OA disease activity as assessed by PtGA at Week 12. The PtGA completed using a 100 mm visual analog scale (VAS) adapted from the Patient Assessment Form © 1999, American College of Rheumatology. The subject rated how well he/she was doing, considering all the ways in which illness and health conditions may affected him/her. The VAS scale was anchored by Very Well on the left (scored as 0) and Very Poorly on the right (scored as 100). Higher scores indicated poorer disease assessment by the subject.
Time frame: Baseline and Week 12
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.03 mg SM04690 | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -16.2 score on a scale | Standard Deviation 25 |
| 0.07 mg SM04690 | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -20.0 score on a scale | Standard Deviation 28 |
| 0.15 mg SM04690 | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -10.9 score on a scale | Standard Deviation 23.4 |
| 0.23 mg SM04690 | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -18.4 score on a scale | Standard Deviation 24.9 |
| Placebo | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -12.7 score on a scale | Standard Deviation 21.9 |
| Sham | Change From Baseline OA Disease Activity as Assessed by Patient Global Assessment (PtGA) | -12.7 score on a scale | Standard Deviation 22.9 |
p-value: 0.25495% CI: [-9.04, 2.4]ANCOVA
p-value: 0.03195% CI: [-13.1, -0.63]ANCOVA
p-value: 0.61695% CI: [-7.2, 4.28]ANCOVA
p-value: 0.0195% CI: [-13.41, -1.82]ANCOVA
p-value: 0.96195% CI: [-5.74, 5.46]ANCOVA
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 \[0 = no functional disability, 100 = unable to function\].
Time frame: Baseline and Week 12
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.03 mg SM04690 | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -26.0 score on a scale | Standard Deviation 19 |
| 0.07 mg SM04690 | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -29.3 score on a scale | Standard Deviation 21.8 |
| 0.15 mg SM04690 | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -20.9 score on a scale | Standard Deviation 20.2 |
| 0.23 mg SM04690 | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -30.4 score on a scale | Standard Deviation 21.3 |
| Placebo | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -22.7 score on a scale | Standard Deviation 23.2 |
| Sham | Change From Baseline OA Function in the Target Knee as Assessed by WOMAC Physical Function Subscore (WOMAC Function) | -22.7 score on a scale | Standard Deviation 24.2 |
p-value: 0.29995% CI: [-8.83, 2.73]ANCOVA
p-value: 0.02195% CI: [-13.24, -1.12]ANCOVA
p-value: 0.67595% CI: [-4.75, 7.33]ANCOVA
p-value: 0.00695% CI: [-14.7, -2.55]ANCOVA
p-value: 0.92595% CI: [-5.99, 6.59]ANCOVA
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 \[0 = no pain, 100 = pain as bad as it can be\].
Time frame: Baseline and Week 12
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.03 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assessed by WOMAC Pain Subscore (WOMAC Pain) | -25.8 score on a scale | Standard Deviation 20.5 |
| 0.07 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assessed by WOMAC Pain Subscore (WOMAC Pain) | -29.3 score on a scale | Standard Deviation 21.5 |
| 0.15 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assessed by WOMAC Pain Subscore (WOMAC Pain) | -22.1 score on a scale | Standard Deviation 20.2 |
| 0.23 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assessed by WOMAC Pain Subscore (WOMAC Pain) | -32.1 score on a scale | Standard Deviation 21.2 |
| Placebo | Change From Baseline OA Pain in the Target Knee as Assessed by WOMAC Pain Subscore (WOMAC Pain) | -23.7 score on a scale | Standard Deviation 24.6 |
| Sham | Change From Baseline OA Pain in the Target Knee as Assessed by WOMAC Pain Subscore (WOMAC Pain) | -22.8 score on a scale | Standard Deviation 23.2 |
p-value: 0.47395% CI: [-7.99, 3.72]ANCOVA
p-value: 0.0495% CI: [-12.33, -0.29]ANCOVA
p-value: 0.57795% CI: [-4.35, 7.79]ANCOVA
p-value: 0.00395% CI: [-14.9, -3.01]ANCOVA
p-value: 0.94795% CI: [-6.37, 5.96]ANCOVA
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).
Time frame: Baseline and Week 12
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.03 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS | -2.75 score on a scale | Standard Deviation 2.22 |
| 0.07 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS | -3.02 score on a scale | Standard Deviation 2.03 |
| 0.15 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS | -2.21 score on a scale | Standard Deviation 2.23 |
| 0.23 mg SM04690 | Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS | -2.87 score on a scale | Standard Deviation 2.1 |
| Placebo | Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS | -2.15 score on a scale | Standard Deviation 2.39 |
| Sham | Change From Baseline OA Pain in the Target Knee as Assesses by the Weekly Average of Daily Pain NRS | -2.27 score on a scale | Standard Deviation 2.27 |
p-value: 0.06295% CI: [-1.18, 0.03]ANCOVA
p-value: 0.00195% CI: [-1.54, -0.37]ANCOVA
p-value: 0.69395% CI: [-0.75, 0.5]ANCOVA
p-value: 0.01295% CI: [-1.39, -0.17]ANCOVA
p-value: 0.69795% CI: [-0.49, 0.74]ANCOVA