A Phase 2, Open Label, Pharmacokinetic (PK) Study of TLC599 in Subjects With Osteoarthritis of the Knee

A Phase 2, Open-label, Pharmacokinetic (PK) Study of a Single Intra-articular Administration of TLC599 in Subjects With Mild to Moderate Osteoarthritis of the Knee

This study is a multi-center, Phase 2, open-label, 1-period, parallel study with 9 cohorts of subjects with osteoarthritis (OA) of the knee enrolled to receive single-dose of TLC599 or Dexamethasone sodium phosphate (DSP) via IA injection and 1 cohort of healthy subjects to receive single-dose of DSP via intravenous (IV) injection.

Study Overview

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

Detailed Description

This Phase 2, open-label, 1 period, parallel study will enroll

1. approximately 90 subjects to receive a single dose of TLC599 or DSP via intra-articular (IA) injection, followed by a PK evaluation period up to 24 weeks and an additional follow-up period of 1 to 5 weeks. Additional subjects may be recruited as needed to achieve at least 10 subjects completing the 1-week blood collection period for each treatment.
2. approximately 12 healthy subjects to receive a single dose of DSP via IV injection, followed by a PK evaluation period up to 1 week and an additional follow-up period of 1 week. Additional subjects may be recruited as needed to achieve at least 12 subjects completing the 48-hour blood collection period for IV DSP.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital
  • Taipei City, Taiwan, 114
    • Tri-Service General Hospital
  • Taipei City, Taiwan, 116
    • Taipei Municipal Wanfang Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
  • Florida
    • Miami, Florida, United States, 33014
      • Panax Clinical Research
    • Miami, Florida, United States, 33136
      • South Coast Research Center
    • Miami, Florida, United States, 33136
      • Syneos Health
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina
  • Texas
    • McAllen, Texas, United States, 78501
      • Futuro Clinical Trials, LLC.
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Study Criteria for Patients with OA of the Knee (Cohort G1-G9)

Inclusion Criteria:

• Age 45 or older, non or moderate smokers, body mass index (BMI) ≤ 40.0 kg/m2.
• Knee OA symptoms with confirmed mild to moderate OA.
• Study knee OA severity grade 1-3 (Kellgren-Lawrence).
• Agree to use contraception

Exclusion Criteria:

• Clinically significant (CS) abnormalities (physical, lab, hepatitis B/C, HIV, electrocardiogram [ECG], vital sign or unstable illness).
• Positive urine drug screen, tuberculosis (TB) test; significant alcohol/drug abuse
• Allergic reactions to TLC599, its components, related drugs or cosyntropin.
• History of autoimmune disease, immunodeficiency diseases, treated malignancy, CS opportunistic infection, tuberculosis, infective arthritis or concurrent knee infection
• Intra-articular bleeding in study knee.
• Skin issues at injection site or hindrance to knee joint penetration.
• Blood coagulation disorders.
• Stroke or myocardial infarction
• Poorly controlled hypertension or vital sign abnormalities.
• Interfering conditions with dosing, visits, or compliance or refusal of synovial fluid collection.
• Medication: Strong/moderate Cytochrome P450 (CYP) 3A/3A4 inhibitors/inducers, prescription meds, over-the-counter (OTC)/natural health products, meds affecting platelet function, depot injection/implant, IA corticosteroid, hyaluronic acid, or other injection in study knee, impact on endogenous steroid levels, systemic corticosteroids, live attenuated vaccine, chemotherapeutic/immunosuppressant use for inflammatory diseases.
• Plasma donation or significant blood loss.
• Pregnancy, breastfeeding, or planning to be pregnant/breastfeed
• Serious local/systemic infection or symptomatic viral/bacterial infection
• Severe OA (grade 4) in non-study knee (Kellgren-Lawrence).
• Recent surgery, scheduled knee replacement or lower limb amputation.
• Known/adrenal insufficiency risk.
• Recent participation in other study research

Study Criteria for Healthy Subjects (Cohort G10)

Inclusion Criteria:

• Age 18-45, non-smokers, BMI 18.5-25 kg/m2, body weight ≥ 50.0 kg (males) or ≥ 45.0 kg (females).
• Healthy with no CS illness/surgery within 4 weeks or CS medical history.
• Agree to use contraception
• No new tattoos/body piercings at the injection site until the study ends.

Exclusion Criteria:

• CS abnormal physical, ECG or vital sign findings.
• Known/adrenal insufficiency risk.
• Abnormal lab results (HBV, HCV, HIV, TB).
• Positive pregnancy test or lactating; positive urine drug screen or cotinine test.
• Significant alcohol/drug abuse or positive alcohol test.
• Significant drug allergies or allergic reactions to DSP, dexamethasone, cosyntropin, natural adrenocorticotropic hormone (ACTH), or other related drugs.
• History/presence of conditions including CS opportunistic infection, serious local/systemic infection, autoimmune, blood, heart, vascular, respiratory, lung, skin, liver, gallbladder, retinopathy, neuromuscular, cancer, kidney, diabetes, severe allergic reactions, or others that would preclude participation.
• Fever
• Active/latent tuberculosis or symptomatic viral/bacterial infection
• Medication: Depot injection/implant, vaccine, drug known to induce or inhibit CYP3A4 metabolism, prescription meds, OTC/natural health products.
• Consumption of specified fruits.
• Recent participation in other study research
• Plasma donation or significant blood loss.
• Reasons preventing study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TLC599 12 mg; 12 mg TLC590 (proprietary lipid formulation that consists of 12 mg DSP [active ingredient] with 100 μmol phospholipid) via IA injection in patients with OA of the knee. This 12 mg TLC599 treatment arm consists of six (6) cohorts (G1 to G6), each with different follow-up periods or visit schedules. However, the results will be pooled into a single treatment arm to allow for meaningful analysis across the various synovial fluid (SF) time points, as each subject only has one opportunity to collect an SF sample.	Drug: TLC599; TLC599 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient).; Other Names: TLC599 Injection
Experimental: TLC599 6 mg; 6 mg TLC590 (proprietary lipid formulation that consists of 6 mg DSP [active ingredient] with 50 μmol phospholipid) via IA injection in patients with OA of the knee. This 6 mg TLC599 treatment arm consists of two (2) cohorts (G7 and G8), each with different follow-up periods or visit schedules. However, the results will be pooled into a single treatment arm to allow for meaningful analysis across the various synovial fluid (SF) time points, as each subject only has one opportunity to collect an SF sample.	Drug: TLC599; TLC599 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient).; Other Names: TLC599 Injection
Active Comparator: DSP 4 mg; Dexamethasone Sodium Phosphate (DSP) at a concentration of 4 mg/mL, 1 mL for a total of 4 mg DSP via IA injection in patients with OA of the knee (G9).	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
Active Comparator: DSP 10 mg; Dexamethasone Sodium Phosphate (DSP) at a concentration of 4 mg/mL, 2.5 mL for the total of 10 mg DSP via IV injection in healthy subjects (G10).	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax: maximum concentration	Maximum concentration	Baseline till 24 weeks post IP administration
Tmax: time to peak concentration	Time to peak concentration	Baseline till 24 weeks post IP administration
Area under the Curve [AUC]	Area under the concentration-time curve	Baseline till 24 weeks post investigational product (IP) administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortisol concentration	Cortisol concentration	baseline till 24 weeks post IP administration
Number of adverse events (AEs), including serious adverse event (SAE) and treatment-emergent AE	Number of AEs, including SAE and treatment-emergent AE	Screening till 25 weeks post IP administration

Collaborators and Investigators

• Sponsor: Taiwan Liposome Company
• Investigators: Study Director: Terry Tai, MD, Taiwan Liposome Company

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2019
• Primary Completion (Actual): November 7, 2023
• Study Completion (Actual): November 7, 2023

Study Registration Dates

• First Submitted: November 16, 2018
• First Submitted That Met QC Criteria: November 22, 2018
• First Posted (Actual): November 27, 2018

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 22, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Enzyme Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Dexamethasone 21-phosphate
• Other Study ID Numbers: TLC599A2004

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