Extended and Controlled Release Liposomal Formulated Dexamethasone for Chronic Knee OA Pain (EXCELLENCE)

A Phase 3, Randomized, Double-blind, Placebo- and Active-controlled Study to Evaluate the Efficacy and Safety of TLC599 in Patients With Osteoarthritis of the Knee

Phase 3 randomized, double-blind, placebo- and active comparator-controlled study of TLC599.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis of the Knee
• Intervention / Treatment: Drug: DSP; Drug: TLC599; Other: Normal Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 504
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Broadmeadow, New South Wales, Australia, 2292
      • Genesis Research Services
    • Maroubra, New South Wales, Australia, 2035
      • Australian Clinical Research Network
    • Saint Leonards, New South Wales, Australia, 2065
      • Northern Sydney Local Health District
  • Queensland
    • Taringa, Queensland, Australia, 4068
      • Austrials
  • Western Australia
    • Victoria Park, Western Australia, Australia, 6100
      • Colin Bayliss Research and Teaching Unit
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35242
      • Cahaba Research, Inc
    • Birmingham, Alabama, United States, 35243
      • Affinity Orthopedic Specialists Llc
    • Sheffield, Alabama, United States, 35660
      • Shoals Medical Trials Inc
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
    • Phoenix, Arizona, United States, 85037
      • Gb Family Care
    • Surprise, Arizona, United States, 85374
      • Clinical Research Institute of Arizona Llc
    • Tucson, Arizona, United States, 85704
      • Noble Clinical Research Llc
  • California
    • La Mesa, California, United States, 919142
      • BioSolutions Clinical Research Center
    • North Hollywood, California, United States, 91606
      • Translational Reseach Group Inc Dba Providence Clinical Research
    • Rancho Cucamonga, California, United States, 91730
      • Prospective Research Innovations Inc
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research LLC
  • Florida
    • Clearwater, Florida, United States, 32789
      • Tampa Bay Medical Research
    • DeLand, Florida, United States, 32720
      • University Clinical Research-Deland, Llc Dba Accel Clinical Research
    • Jacksonville, Florida, United States, 33216
      • Jacksonville Center for Clinical Research
    • Lady Lake, Florida, United States, 32159
      • Charter Research, LLC
    • Miami, Florida, United States, 33143
      • Well Pharma Medical Research Corp
    • Orlando, Florida, United States, 32822
      • Conquest Research, LLC
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida
    • Winter Park, Florida, United States, 32789
      • Conquest Research (Winter Park)
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Drug Studies America
    • Marietta, Georgia, United States, 30060
      • Georgia Institute For Clinical Research Llc
    • Newnan, Georgia, United States, 30265
      • Better Health Clinical Research Inc
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60607
      • Chicago Clinical Research Institute, Inc.
    • Flossmoor, Illinois, United States, 60422
      • Healthcare Research Network II, LLC
    • Oak Brook, Illinois, United States, 60523
      • Affinity Health
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center LLC
  • Kansas
    • Wichita, Kansas, United States, 67205
      • Professional Research Network of Kansas Llc
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • DelRicht Research
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Healthcare Research Network
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
  • New York
    • Hartsdale, New York, United States, 10530
      • Drug Trials America
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research LLC
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Lowcountry Orthopedics C/O Coastal Carolina research center
  • Texas
    • Plano, Texas, United States, 75075
      • Clinical Investigations of Texas
    • San Antonio, Texas, United States, 78209
      • Quality Research Inc
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas Inc (Ctt)
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TLC599; TLC599 (1mL) IA injection	Drug: TLC599; TLC599 is a proprietary (Bioseizer) lipid formulation containing DSP (active ingredient); Other Names: TLC599 Injection
Active Comparator: Dexamethasone sodium phosphate; DSP 4mg (1mL) IA injection	Drug: DSP; 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.; Other Names: Dexamethasone Sodium Phosphate; Drug: TLC599; TLC599 is a proprietary (Bioseizer) lipid formulation containing DSP (active ingredient); Other Names: TLC599 Injection
Placebo Comparator: Normal Saline; Normal saline (1mL) IA injection	Other: Normal Saline; 0.9% normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 16
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.	Baseline, Week 20
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.	Baseline, Week 24
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.	Baseline, Week 36
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.	Baseline, Week 12
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".	Week 12
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.	through Week 12
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).	Weeks 4 through 12
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.	Baseline, Week 36
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".	Week 36
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.	Baseline, Week 12
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.	Baseline, Week 52

Collaborators and Investigators

• Sponsor: Taiwan Liposome Company
• Investigators: Study Director: Carl Brown, PhD, Taiwan Liposome Company

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2019
• Primary Completion (Actual): February 3, 2022
• Study Completion (Actual): February 3, 2022

Study Registration Dates

• First Submitted: October 9, 2019
• First Submitted That Met QC Criteria: October 9, 2019
• First Posted (Actual): October 11, 2019

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: September 12, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Dexamethasone 21-phosphate
• Other Study ID Numbers: TLC599A3005

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