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

Study Purpose

This study is a single-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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 50 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Male or female non or moderate smokers, 50 years or older, with BMI ≤ 40.0 kg/m2. 2. Has symptoms associated with OA of the knee for at least 6 months prior to Screening and confirmation of mild to moderate OA. 3. The study knee has OA with grade 1-3 in severity based on the Kellgren-Lawrence grades. 4. Females of childbearing potential to use acceptable contraceptive methods for 21 weeks after study drug administration. 5. Male subjects must to use acceptable contraceptive methods from dosing until 21 weeks after study drug administration. 6. Willing and able to comply with study procedures and provide written informed consent.

Exclusion Criteria:

1. Clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results or positive test for hepatitis B, hepatitis C, or HIV found during screening. 2. Positive urine drug screen at screening. 3. History of allergic reactions to TLC599, its components or other related drugs. 4. Clinically significant and unstable illness. 5. History of clinically significant autoimmune disease. 6. Evidence of intra articular bleeding of the study knee at baseline prior to study drug administration. 7. History of infective arthritis or suspected / concurrent infection in the study knee at baseline prior to study drug administration; clinical symptoms and signs of acute infection or infection-related inflammation in the non-study knee before study drug administration. 8. Skin lesion/breakdown at the anticipated injection site or any condition that would impair penetration of the study knee joint space. 9. Platelet count < 80,000/μL, or blood coagulation disorders at the Screening. 10. Total white blood cell count <3000/ μL or >13000/ μL. 11. History of acquired or congenital immunodeficiency diseases. 12. History of treated malignancy which is disease free for ≤ 5 years prior to the Screening, except for basal cell carcinoma and squamous cell carcinoma of skin or carcinoma in situ of the uterine cervix. 13. Stroke or myocardial infarction within 3 months prior to the Screening. 14. Subjects with a condition or in a situation which will interfere with the subject's ability to comply or cooperate with the dosing and visit schedules and the protocol evaluations or may not be suitable for this study. 15. Clinically significant ECG abnormalities or vital sign abnormalities at screening. 16. History of significant alcohol abuse within one year prior to the Screening or regular use of alcohol within six months prior to the Screening. 17. History of significant drug abuse within one year prior to the Screening or use of soft drugs within 3 months prior to the Screening or hard drugs within 1 year prior to the Screening. 18. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to dosing, administration of a biological product in the context of a clinical research study within 90 days prior to dosing, or concomitant participation in an investigational study involving no drug or device administration. 19. Any use of medication; 1. drugs known to induce or inhibit hepatic CYP 3A4 metabolism within 30 days prior to dosing; 2. prescription medication within 14 days prior to dosing; 3. over-the-counter products and natural health products within 7 days prior to dosing; 4. prescription medication known to affect platelet function within 14 days prior to dosing; 5. a depot injection or an implant of any drug within 3 months prior to dosing; 6. use of IA corticosteroid, hyaluronic acid, or other IA injection in the study knee within 4 months prior to dosing; 7. any IA injection drug that could impact endogenous steroid levels within 6 months prior to dosing; 8. systemic corticosteroids within 30 days prior to dosing; 9. use of any chemotherapeutic or systemic immunosuppressant agents for inflammatory diseases within 6 months prior to dosing. 20. Donation of plasma within 7 days prior to dosing. Donation or loss of blood of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to dosing. 21. Female subjects who are pregnant, breast-feeding, or plan to become pregnant/breast-feeding. 22. History of latent or active tuberculosis or exposure to endemic areas within 8 weeks prior to the Screening. 23. Positive QuantiFERON®-TB test indicating possible tuberculosis infection at the Screening. 24. Immunization with a live attenuated vaccine 1 month prior to dosing or planned vaccination during the course of the study. 25. History of clinically significant opportunistic infection. 26. Serious local infection or systemic infection within the 3 months prior to the Screening. 27. Presence of fever associated with a symptomatic viral or bacterial infection within 2 weeks prior to dosing. 28. Subjects with previous diagnosis of severe OA with grade 4 classification based on the Kellgren-Lawrence grades. 29. Subject who had a surgery within 4 weeks prior to dosing or expected to have a knee replacement surgery scheduled within 21 weeks after the study drug administration.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03754049
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Taiwan Liposome Company
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Carl Brown, PhD
Principal Investigator Affiliation Taiwan Liposome Company
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

OSTEOARTHRITIS OF THE KNEE
Additional Details

This single center, Phase 2, open-label, 1 period, parallel study will enroll 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 will be recruited as needed, to achieve at least 6 subjects per cohort with adequate SF volume for DP and DEX concentration analysis at EOPK.

Arms & Interventions

Arms

Experimental: TLC599 12 mg

12 mg DSP with 100 μmol phospholipid via IA injection;

Experimental: TLC599 6 mg

6 mg DSP with 50 μmol phospholipid via IA injection.

Active Comparator: DSP 4mg

Dexamethasone Sodium Phosphate (DSP): 4 mg/mL, 1 mL via IA injection.

Interventions

Drug: - TLC599

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

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Panax Clinical Research, Miami, Florida

Status

Recruiting

Address

Panax Clinical Research

Miami, Florida, 33014

Site Contact

Wyatt, MD

chengyu@tlcbio.com

305-698-4500

South Coast Research Center, Miami, Florida

Status

Recruiting

Address

South Coast Research Center

Miami, Florida, 33136

Site Contact

Wyatt, MD

chengyu@tlcbio.com

786-343-6937

Syneos Health, Miami, Florida

Status

Recruiting

Address

Syneos Health

Miami, Florida, 33136

Site Contact

Wyatt, MD

chengyu@tlcbio.com

305-547-5800