Phase IIa, Randomized, Double Blinded, Placebo Controlled, Dose Finding Study for TLC599 in OA Patients

A Phase IIa, Randomized, Double Blinded, Placebo Controlled, Dose Finding Study for Single Dose Administration of TLC599 in Patients With Osteoarthritis (OA) of Knee

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis of the Knee
• Intervention / Treatment: Drug: TLC599 LD group; Drug: TLC599 HD group; Drug: Normal Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Broadmeadow, Australia
    • Genesis Research Services Pty Limited
  • Cardiff, Australia, 2285
    • Pendlebury Clinic Private Hospital
  • Footscray, Australia
    • Footscray Hospital- Western Health
  • Nedlands,, Australia
    • Linear Clinical Research Limited
  • Sydney, Australia
    • Royal North Shore Hospital
• Taiwan
  • Changhua, Taiwan
    • Show Chwan Memorial Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 402
    • Chung Shan Medical University Hosptial
  • Taipei, Taiwan
    • Cheng Hsin General Hospital
  • Taipei, Taiwan
    • Shin Kong Wu Ho-Su Memorial Hospital
  • Taipei, Taiwan
    • Taipei Medical Universtiy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TLC599 LD group; 12 mg DSP with 100 µmol PL (1.0 mL)	Drug: TLC599 LD group; Single dose via intra-articular injection; Other Names: 12 mg DSP with 100 µmol PL (1.0 mL)
Experimental: TLC599 HD group; 18 mg DSP with 150 µmol PL (1.5 mL)	Drug: TLC599 HD group; Single dose via intra-articular injection; Other Names: 18 mg DSP with 150 µmol PL (1.5 mL)
Placebo Comparator: Placebo group; 1.5 mL normal saline	Drug: Normal Saline; Single dose via intra-articular injection; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC questionnaire pain sub-scale	Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in pain / function subscales of WOMAC.	at Weeks 1, 4, 8, 12, 16, 20, and 24
Pain score (VAS)	Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS).	at Weeks 1, 4, 8, 12, 16, 20, and 24
Pain score (VAS)	Change from baseline through Weeks 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS).	from dosing through Week 12, 16, 20, 24
WOMAC questionnaire pain sub-scale	Change from baseline through Weeks 12, 16, 20, and 24 in the patient rated visual analogue scale (VAS).	from dosing through Week 12, 16, 20, 24
EuroQol-5 Dimension questionnaire	Change from baseline to Weeks 1, 4, 8, 12, 16, 20, and 24 in EuroQol-5 Dimension questionnaire.	at Weeks 1, 4, 8, 12, 16, 20, and 24
Usage of acetaminophen	Total consumption of acetaminophen at Weeks 1, 4, 8, 12, 16, 20, and 24.	at Weeks 1, 4, 8, 12, 16, 20, and 24
Incidence of Treatment-Emergent Adverse Events	To evaluate the safety and tolerability of TLC599 by incidence of Treatment-Emergent Adverse Events reported by Investigators	up to 24 weeks after dosing

Collaborators and Investigators

• Sponsor: Taiwan Liposome Company
• Investigators: Study Director: Yvonne Shih, PhD, Taiwan Liposome Company

Publications and helpful links

General Publications

• Hunter DJ, Chang CC, Wei JC, Lin HY, Brown C, Tai TT, Wu CF, Chuang WC, Shih SF. TLC599 in patients with osteoarthritis of the knee: a phase IIa, randomized, placebo-controlled, dose-finding study. Arthritis Res Ther. 2022 Feb 21;24(1):52. doi: 10.1186/s13075-022-02739-4.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2017
• Primary Completion (Actual): July 4, 2018
• Study Completion (Actual): July 4, 2018

Study Registration Dates

• First Submitted: December 12, 2016
• First Submitted That Met QC Criteria: December 26, 2016
• First Posted (Estimated): December 29, 2016

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Dexamethasone; osteoarthritis of the knee; DSP; TLC599
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: TLC599A2003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No