Osteoarthritis of the Knee
Conditions
Brief summary
Phase 3 randomized, double-blind, placebo- and active comparator-controlled study of TLC599.
Detailed description
This is a Phase 3 randomized, double-blind, placebo- and active comparator-controlled pivotal study. Approximately 500 adult patients with moderate to severe pain due to OA of the knee will be enrolled and randomized. All patients will be followed for a total of 52 weeks. Efficacy and safety of 2 doses of TLC599 will be evaluated in comparison to Placebo and DSP through Week 52.
Interventions
DRUGTLC599
TLC599 is a proprietary (Bioseizer) lipid formulation containing DSP (active ingredient)
DRUGDSP
Dexamethasone sodium phosphate (DSP) is a glucocorticoid widely used in the treatment of joint pain such as gout, osteoarthritis and rheumatoid arthritis via IA injection.
OTHERNormal Saline
0.9% normal saline
Sponsors
Taiwan Liposome Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Male or female ≥40 years of age. BMI ≤ 40 kg/m2. Radiographically documented OA with Kellgren-Lawrence severity Grade 2 or 3 and associated symptoms Patient-reported pain with NRS score ≥4 (on a 0-10 scale) Able to read, understand, and sign the informed consent form, communicate with the investigator, complete study diaries, and understand and comply with protocol requirements.
Exclusion criteria
Recent use of IA or systemic corticosteroids Patient who is not ambulatory Any surgery or arthroscopy in the index knee within 12 months Any condition that could possibly confound the patient's assessment of index knee pain Substance abuse disorder, or positive urine drug test for illegal drug substances History of acquired or congenital immunodeficiency diseases History of treated malignancy which is disease free for ≤5 years Known allergy or hypersensitivity to the study drugs or their components
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in WOMAC Pain at Week 12 for TLC599 12 mg Versus Placebo | Baseline, Week 12 | The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in WOMAC Pain at Week 20 for TLC599 12 mg Versus Placebo | Baseline, Week 20 | The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity. |
| Change From Baseline in WOMAC Pain at Week 24 for TLC599 12mg Versus Placebo | Baseline, Week 24 | The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity. |
| Change From Baseline in WOMAC Pain at Week 36 for TLC599 12mg Versus Placebo | Baseline, Week 36 | The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity. |
| Change From Baseline in WOMAC Function at Week 12 for TLC599 12mg Versus Placebo | Baseline, Week 12 | The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity. |
| PGIC at Week 12 for TLC599 12mg Versus Placebo | Week 12 | Patient Global Impression of Change (PGIC) is a single-item question that measures change in patients' overall improvement rated on a 7-point scale including 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, or 7 = very much worse. |
| Change From Baseline in WOMAC Pain at Week 16 for TLC599 12 mg Versus Placebo | Baseline, Week 16 | The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity. |
| Durable Responder With ≥30% Decrease in WOMAC Pain From Baseline for Weeks 4 Through 12 for TLC599 12mg Versus Placebo | Weeks 4 through 12 | Durable responder endpoints were derived based on the imputed WOMAC pain data. A subject which has ≥ 30% decrease in pain response from Baseline at each visit within a specified time period (x-y). This was derived for patients based on the Injection 1 Baseline for the following time period (x-y): (4-12). |
| Change From Baseline in WOMAC Function at Week 36 for TLC599 12mg Versus Placebo | Baseline, Week 36 | The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity. |
| PGIC at Week 36 for TLC599 12mg Versus Placebo | Week 36 | Patient Global Impression of Change (PGIC) is a single-item question that measures change in patients' overall improvement rated on a 7-point scale including 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, or 7 = very much worse. |
| Change From Baseline in WOMAC Pain at Week 12 for TLC599 12mg Versus DSP 4 mg | Baseline, Week 12 | The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity. |
| Change From Baseline in WOMAC Pain at Week 52 for TLC599 12mg Versus Placebo | Baseline, Week 52 | The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity. |
| Total Rescue Acetaminophen Consumption Through Week 12 for TLC599 12mg Versus Placebo | through Week 12 | Rescue medication use of acetaminophen was provided and recorded in electronic patient diaries. Weekly Total Acetaminophen consumption was tabulated for analysis on a weekly basis, starting from the first date of study drug injection: (Day 1, 8), (Day 8, 15), and so on. Average daily use (e.g., Weekly Total Acetaminophen Consumption divided by 7) was computed to produce Weekly Average Daily Acetaminophen Consumption. |
Countries
Australia, United States
Participant flow
Recruitment details
Patients were screened for study eligibility at multiple study centers in the United States (US) and Australia.
Participants by arm
| Arm | Count |
|---|---|
| TLC599 12 mg TLC599:1 mL IA injection
TLC599 is a proprietary (Bioseizer) lipid formulation containing DSP (active ingredient) | 252 |
| DSP 4 mg DSP 4mg:1 mL IA injection Dexamethasone sodium phosphate (DSP) is a glucocorticoid widely used in the treatment of joint pain such as gout, osteoarthritis and rheumatoid arthritis via IA injection. | 126 |
| Placebo Normal saline: 1 mL IA injection | 126 |
| Total | 504 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 | 3 |
| Overall Study | A surgical procedure or IA administration in the index knee | 3 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 7 | 8 | 6 |
| Overall Study | Lost to Follow-up | 20 | 12 | 5 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 7 | 9 |
Baseline characteristics
| Characteristic | TLC599 12 mg | Total | Placebo | DSP 4 mg |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 90 Participants | 182 Participants | 47 Participants | 45 Participants |
| Age, Categorical Between 18 and 65 years | 162 Participants | 322 Participants | 79 Participants | 81 Participants |
| Age, Continuous | 61.5 years STANDARD_DEVIATION 8.5 | 61.0 years STANDARD_DEVIATION 8.97 | 61.3 years STANDARD_DEVIATION 9.3 | 59.9 years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants | 79 Participants | 18 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 207 Participants | 422 Participants | 108 Participants | 107 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 2 Participants |
| Mean body mass index | 31.13 kg/m^2 STANDARD_DEVIATION 4.772 | 31.35 kg/m^2 STANDARD_DEVIATION 4.825 | 31.33 kg/m^2 STANDARD_DEVIATION 4.603 | 31.80 kg/m^2 STANDARD_DEVIATION 5.144 |
| Mean weight | 89.30 Kg STANDARD_DEVIATION 17.816 | 89.96 Kg STANDARD_DEVIATION 18.207 | 89.55 Kg STANDARD_DEVIATION 17.75 | 91.71 Kg STANDARD_DEVIATION 19.425 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 4 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 18 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 48 Participants | 94 Participants | 20 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 195 Participants | 384 Participants | 95 Participants | 94 Participants |
| Region of Enrollment Australia | 28 participants | 57 participants | 17 participants | 12 participants |
| Region of Enrollment United States | 224 participants | 447 participants | 109 participants | 114 participants |
| Sex: Female, Male Female | 146 Participants | 296 Participants | 79 Participants | 71 Participants |
| Sex: Female, Male Male | 106 Participants | 208 Participants | 47 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 252 | 0 / 126 | 1 / 126 |
| other Total, other adverse events | 73 / 252 | 33 / 126 | 28 / 126 |
| serious Total, serious adverse events | 16 / 252 | 4 / 126 | 7 / 126 |
Outcome results
Primary
Change From Baseline in WOMAC Pain at Week 12 for TLC599 12 mg Versus Placebo
The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity.
Time frame: Baseline, Week 12
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TLC599 12mg | Change From Baseline in WOMAC Pain at Week 12 for TLC599 12 mg Versus Placebo | -0.968 score on a scale |
| Placebo | Change From Baseline in WOMAC Pain at Week 12 for TLC599 12 mg Versus Placebo | -0.798 score on a scale |
p-value: 0.037295% CI: [-0.331, -0.01]ANCOVA
Secondary
Change From Baseline in WOMAC Function at Week 12 for TLC599 12mg Versus Placebo
The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity.
Time frame: Baseline, Week 12
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 12mg | Change From Baseline in WOMAC Function at Week 12 for TLC599 12mg Versus Placebo | -0.903 score on a scale | Standard Error 0.047 |
| Placebo | Change From Baseline in WOMAC Function at Week 12 for TLC599 12mg Versus Placebo | -0.735 score on a scale | Standard Error 0.0681 |
Secondary
Change From Baseline in WOMAC Function at Week 36 for TLC599 12mg Versus Placebo
The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity.
Time frame: Baseline, Week 36
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 12mg | Change From Baseline in WOMAC Function at Week 36 for TLC599 12mg Versus Placebo | -0.907 score on a scale | Standard Error 0.054 |
| Placebo | Change From Baseline in WOMAC Function at Week 36 for TLC599 12mg Versus Placebo | -0.787 score on a scale | Standard Error 0.0774 |
Secondary
Change From Baseline in WOMAC Pain at Week 12 for TLC599 12mg Versus DSP 4 mg
The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity.
Time frame: Baseline, Week 12
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 12mg | Change From Baseline in WOMAC Pain at Week 12 for TLC599 12mg Versus DSP 4 mg | -0.968 score on a scale | Standard Error 0.0467 |
| Placebo | Change From Baseline in WOMAC Pain at Week 12 for TLC599 12mg Versus DSP 4 mg | -0.933 score on a scale | Standard Error 0.0667 |
Secondary
Change From Baseline in WOMAC Pain at Week 16 for TLC599 12 mg Versus Placebo
The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity.
Time frame: Baseline, Week 16
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 12mg | Change From Baseline in WOMAC Pain at Week 16 for TLC599 12 mg Versus Placebo | -0.929 score on a scale | Standard Error 0.0492 |
| Placebo | Change From Baseline in WOMAC Pain at Week 16 for TLC599 12 mg Versus Placebo | -0.798 score on a scale | Standard Error 0.0704 |
Secondary
Change From Baseline in WOMAC Pain at Week 20 for TLC599 12 mg Versus Placebo
The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity.
Time frame: Baseline, Week 20
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 12mg | Change From Baseline in WOMAC Pain at Week 20 for TLC599 12 mg Versus Placebo | -0.873 score on a scale | Standard Error 0.0489 |
| Placebo | Change From Baseline in WOMAC Pain at Week 20 for TLC599 12 mg Versus Placebo | -0.749 score on a scale | Standard Error 0.0703 |
Secondary
Change From Baseline in WOMAC Pain at Week 24 for TLC599 12mg Versus Placebo
The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity.
Time frame: Baseline, Week 24
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 12mg | Change From Baseline in WOMAC Pain at Week 24 for TLC599 12mg Versus Placebo | -0.845 score on a scale | Standard Error 0.0496 |
| Placebo | Change From Baseline in WOMAC Pain at Week 24 for TLC599 12mg Versus Placebo | -0.688 score on a scale | Standard Error 0.0719 |
Secondary
Change From Baseline in WOMAC Pain at Week 36 for TLC599 12mg Versus Placebo
The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity.
Time frame: Baseline, Week 36
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 12mg | Change From Baseline in WOMAC Pain at Week 36 for TLC599 12mg Versus Placebo | -0.964 score on a scale | Standard Error 0.0545 |
| Placebo | Change From Baseline in WOMAC Pain at Week 36 for TLC599 12mg Versus Placebo | -0.882 score on a scale | Standard Error 0.0791 |
Secondary
Change From Baseline in WOMAC Pain at Week 52 for TLC599 12mg Versus Placebo
The WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index, Version 3.1) consists of 24 questions rated on a 0-4 Likert scale, totaling a score from 0-96, reflecting the previous 24 hours. Sub-scale scores for Pain (5 items, a 0-20 scale), Stiffness (2 items, a 0-8 scale), and Physical Function (17 items, a 0-68 scale) are summed to calculate the WOMAC Composite score. Both composite and sub-scale scores are normalized to a 0-4 scale for analysis, with higher scores indicating greater severity.
Time frame: Baseline, Week 52
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 12mg | Change From Baseline in WOMAC Pain at Week 52 for TLC599 12mg Versus Placebo | -0.928 score on a scale | Standard Error 0.058 |
| Placebo | Change From Baseline in WOMAC Pain at Week 52 for TLC599 12mg Versus Placebo | -0.934 score on a scale | Standard Error 0.082 |
Secondary
Durable Responder With ≥30% Decrease in WOMAC Pain From Baseline for Weeks 4 Through 12 for TLC599 12mg Versus Placebo
Durable responder endpoints were derived based on the imputed WOMAC pain data. A subject which has ≥ 30% decrease in pain response from Baseline at each visit within a specified time period (x-y). This was derived for patients based on the Injection 1 Baseline for the following time period (x-y): (4-12).
Time frame: Weeks 4 through 12
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TLC599 12mg | Durable Responder With ≥30% Decrease in WOMAC Pain From Baseline for Weeks 4 Through 12 for TLC599 12mg Versus Placebo | 45.5 percentage of responder |
| Placebo | Durable Responder With ≥30% Decrease in WOMAC Pain From Baseline for Weeks 4 Through 12 for TLC599 12mg Versus Placebo | 39.0 percentage of responder |
Secondary
PGIC at Week 12 for TLC599 12mg Versus Placebo
Patient Global Impression of Change (PGIC) is a single-item question that measures change in patients' overall improvement rated on a 7-point scale including 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, or 7 = very much worse.
Time frame: Week 12
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 12mg | PGIC at Week 12 for TLC599 12mg Versus Placebo | 2.554 score on a scale | Standard Error 0.0739 |
| Placebo | PGIC at Week 12 for TLC599 12mg Versus Placebo | 2.791 score on a scale | Standard Error 0.1059 |
Secondary
PGIC at Week 36 for TLC599 12mg Versus Placebo
Patient Global Impression of Change (PGIC) is a single-item question that measures change in patients' overall improvement rated on a 7-point scale including 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, or 7 = very much worse.
Time frame: Week 36
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 12mg | PGIC at Week 36 for TLC599 12mg Versus Placebo | 2.635 score on a scale | Standard Error 0.0883 |
| Placebo | PGIC at Week 36 for TLC599 12mg Versus Placebo | 2.738 score on a scale | Standard Error 0.1288 |
Secondary
Total Rescue Acetaminophen Consumption Through Week 12 for TLC599 12mg Versus Placebo
Rescue medication use of acetaminophen was provided and recorded in electronic patient diaries. Weekly Total Acetaminophen consumption was tabulated for analysis on a weekly basis, starting from the first date of study drug injection: (Day 1, 8), (Day 8, 15), and so on. Average daily use (e.g., Weekly Total Acetaminophen Consumption divided by 7) was computed to produce Weekly Average Daily Acetaminophen Consumption.
Time frame: through Week 12
Population: The Full Analysis Set (FAS) includes all randomized patients who receive study drug at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 12mg | Total Rescue Acetaminophen Consumption Through Week 12 for TLC599 12mg Versus Placebo | 15.568 tablets per week | Standard Error 3.1902 |
| Placebo | Total Rescue Acetaminophen Consumption Through Week 12 for TLC599 12mg Versus Placebo | 29.803 tablets per week | Standard Error 4.5893 |