A Phase 2, Open Label, PK Study of TLC599 in Subject With Osteoarthritis of the Knee

OSTEOARTHRITIS OF THE KNEE Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03754049
• Other study ID #: TLC599A2004
• Status: Completed
• Phase: Phase 2
• Start date: January 21, 2019
• Est. completion date: November 7, 2023

Study information

• Verified date: January 2024
• Source: Taiwan Liposome Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 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 recieve 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: November 7, 2023
• Est. primary completion date: November 7, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Cohort G1-G9 Study Criteria

Inclusion Criteria:

• Age 45 or older, non or moderate smokers, 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:

• CS abnormalities (physical, lab, hepatitis B/C, HIV, ECG, vital sign or unstable illness).

• Positive urine drug screen, 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 CYP 3A/3A4 inhibitors/inducers, prescription meds, 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

Cohort G10 (Healthy Subjects) Study Criteria

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 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

Related Conditions & MeSH terms

• Osteoarthritis
• OSTEOARTHRITIS OF THE KNEE
• Osteoarthritis, Knee

Intervention

Drug:
• TLC599
TLC599 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient).
• 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.

Locations

Country	Name	City	State
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taipei Municipal Wanfang Hospital	Taipei City
Taiwan	Tri-Service General Hospital	Taipei City
United States	Clinical Trials of South Carolina	Charleston	South Carolina
United States	Futuro Clinical Trials, LLC.	McAllen	Texas
United States	Panax Clinical Research	Miami	Florida
United States	South Coast Research Center	Miami	Florida
United States	Syneos Health	Miami	Florida
United States	Arizona Research Center	Phoenix	Arizona
United States	JBR Clinical Research	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Taiwan Liposome Company

Countries where clinical trial is conducted

United States,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the Curve [AUC]	Area under the concentration-time curve	Baseline till 24 weeks post IP administration
Primary	Cmax: maximum concentration	Maximum concentration	Baseline till 24 weeks post IP administration
Primary	Tmax: time to peak concentration	Time to peak concentration	Baseline till 24 weeks post IP administration
Secondary	Number of AEs, including SAE and treatment-emergent AE	Number of AEs, including SAE and treatment-emergent AE	Screening till 25 weeks post IP administration
Secondary	Cortisol concentration	Cortisol concentration	baseline till 24 weeks post IP administration