Osteoarthritis of the Knee
Conditions
Keywords
osteoarthritis of the knee, TLC599, Dexamethasone, DSP
Brief summary
This trial is a Phase IIa, Randomized, Double blinded, Placebo controlled, Dose finding Study to investigate the safety and efficacy of TLC599 in subjects with osteoarthritis of the knee.
Detailed description
Protocol No: TLC599A2003 Name of Finished Product: TLC599 Title of Study: A Phase IIa, Randomized, Double blinded, Placebo controlled, Dose finding Study for Single dose Administration of TLC599 in Patients with Osteoarthritis (OA) of Knee. Study duration: The trial will last around 27 weeks including a 21-day screening period and a 24-week follow-up period.
Interventions
DRUGTLC599 LD group
Single dose via intra-articular injection
DRUGNormal Saline
Single dose via intra-articular injection
DRUGTLC599 HD group
Single dose via intra-articular injection
Sponsors
Taiwan Liposome Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Male or female patients, at least 50 years of age. 2. Documented diagnosis of OA of the knee for at least 6 months 3. The study knee has OA with Grade 2 to 3 severity based on the Kellgren Lawrence grades 4. Patients with patient related visual analogue scale (VAS) score of 5.0 to 9.0 at baseline. 5. Willing and able to comply with study procedures and provide written informed consent. Main
Exclusion criteria
1. Patients who received systemic corticosteroids within the last 30 days prior to dosing. 2. Patients who use prohibited medications within 7 days prior to study drug administration or any pain control medication including acetaminophen within 48 hours prior to study drug administration. 3. Patients who use prohibited medications other than acetaminophen and oral NSAIDs from screening visit to 7 days prior to study drug administration. 4. Documented history and confirmed autoimmune disease 5. History of post-traumatic knee arthritis, or evidence of intra articular bleeding of the study knee 6. History of infective arthritis 7. Unstable study knee joint 8. Use of IA corticosteroid, hyaluronic acid, or other IA injection in the study knee within 3 months prior to the screening visit. 9. A history of treated malignancy which is disease free for ≤ 5 years prior to the screening visit 10. Uncontrolled and unstable concurrent medical or psychiatric illness, that will jeopardize the safety of the patient 11. Use of any chemotherapeutic or systemic immunosuppressant agents for inflammatory diseases within 6 months prior to the screening visit. 12. Current use of anticoagulants, including warfarin, heparin, low molecular weight heparin, or dabigatran. 13. Abnormalities of laboratory parameters as described below will qualify for exclusion: * hemoglobin \< 8 g/dL; * total white blood cell count \< 4000/ µL; * serum bilirubin/ alanine aminotransferase/ aspartate aminotransferase \> 2 times upper limit of normal (ULN) for the laboratory reference ranges; * serum creatinine \> 2 times ULN for the laboratory reference range; * serum uric acid \> ULN for the laboratory reference range; * prothrombin time/International Normalized Ratio \> ULN for the laboratory reference range. 14. Contraindication to undergoing magnetic resonance imaging (MRI)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in WOMAC Pain Subscale at Week 12 | Baseline, Week 12 | The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale consist of five items, each ranging from 0 to 4, making the total Pain subscore 0 to 20. The total score of the pain subscale for each patient is normalized and expressed on a 0 to 4 scale. Higher scores represent higher levels of pain (worse outcome), whereas lower scores represent lower levels of pain (better outcome). Missing data were imputed. |
Countries
Australia, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TLC599 LD Group 12 mg DSP with 100 µmol PL (1.0 mL)
TLC599 LD group: Single dose via intra-articular injection | 26 |
| TLC599 HD Group 18 mg DSP with 150 µmol PL (1.5 mL)
TLC599 HD group: Single dose via intra-articular injection | 24 |
| Placebo Group 1.5 mL normal saline
Normal Saline: Single dose via intra-articular injection | 25 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Ineligible post randomization | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Prohibited medication use post radnomization | 1 | 1 | 1 |
| Overall Study | Withdrew consent | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | TLC599 LD Group | TLC599 HD Group | Placebo Group | Total |
|---|---|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 9.07 | 62.9 years STANDARD_DEVIATION 8.8 | 64.8 years STANDARD_DEVIATION 8.45 | 63.9 years STANDARD_DEVIATION 8.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 22 Participants | 24 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Kellgren-Lawrence grades Grade 0 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Kellgren-Lawrence grades Grade 1 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Kellgren-Lawrence grades Grade 2 | 13 Participants | 9 Participants | 9 Participants | 31 Participants |
| Kellgren-Lawrence grades Grade 3 | 13 Participants | 15 Participants | 16 Participants | 44 Participants |
| Kellgren-Lawrence grades Grade 4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 13 Participants | 12 Participants | 38 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 11 Participants | 13 Participants | 37 Participants |
| Region of Enrollment Australia | 13 participants | 12 participants | 13 participants | 38 participants |
| Region of Enrollment Taiwan | 13 participants | 12 participants | 12 participants | 37 participants |
| Sex: Female, Male Female | 15 Participants | 17 Participants | 18 Participants | 50 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 7 Participants | 25 Participants |
| VAS score (Study Knee) | 6.45 units on a scale STANDARD_DEVIATION 1.113 | 6.87 units on a scale STANDARD_DEVIATION 1.215 | 6.56 units on a scale STANDARD_DEVIATION 1.049 | 6.62 units on a scale STANDARD_DEVIATION 1.125 |
| WOMAC Function score (0-4) | 1.53 units on a scale STANDARD_DEVIATION 0.531 | 1.82 units on a scale STANDARD_DEVIATION 0.742 | 1.48 units on a scale STANDARD_DEVIATION 0.652 | 1.61 units on a scale STANDARD_DEVIATION 0.653 |
| WOMAC Pain score (0-4) | 1.49 units on a scale STANDARD_DEVIATION 0.558 | 1.74 units on a scale STANDARD_DEVIATION 0.631 | 1.62 units on a scale STANDARD_DEVIATION 0.609 | 1.62 units on a scale STANDARD_DEVIATION 0.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 24 | 0 / 25 |
| other Total, other adverse events | 18 / 26 | 20 / 24 | 17 / 25 |
| serious Total, serious adverse events | 1 / 26 | 0 / 24 | 0 / 25 |
Outcome results
Primary
Change From Baseline in WOMAC Pain Subscale at Week 12
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale consist of five items, each ranging from 0 to 4, making the total Pain subscore 0 to 20. The total score of the pain subscale for each patient is normalized and expressed on a 0 to 4 scale. Higher scores represent higher levels of pain (worse outcome), whereas lower scores represent lower levels of pain (better outcome). Missing data were imputed.
Time frame: Baseline, Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TLC599 LD Group | Change From Baseline in WOMAC Pain Subscale at Week 12 | -0.83 score on a scale | Standard Error 0.09 |
| TLC599 HD Group | Change From Baseline in WOMAC Pain Subscale at Week 12 | -0.64 score on a scale | Standard Error 0.094 |
| Placebo Group | Change From Baseline in WOMAC Pain Subscale at Week 12 | -0.47 score on a scale | Standard Error 0.092 |