Clinical trial NCT03754049: A Phase 2, Open Label, Pharmacokinetic (PK) Study of TLC599 in Subjects With Osteoarthritis of the Knee
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis of the Knee
Lead sponsor: Taiwan Liposome Company
Sponsor class: INDUSTRY
First posted: 2018-11-27
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Area under the Curve [AUC]
timeFrame: Baseline till 24 weeks post investigational product (IP) administration
measure: Cmax: maximum concentration
timeFrame: Baseline till 24 weeks post IP administration
measure: Tmax: time to peak concentration
timeFrame: Baseline till 24 weeks post IP administration
Secondary outcomes:
measure: Number of adverse events (AEs), including serious adverse event (SAE) and treatment-emergent AE
timeFrame: Screening till 25 weeks post IP administration
measure: Cortisol concentration
timeFrame: baseline till 24 weeks post IP administration
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Miami
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami
country: United States
facility: South Coast Research Center
state: Florida
city: Miami
country: United States
facility: Syneos Health
state: Florida
city: Charleston
country: United States
facility: Clinical Trials of South Carolina
state: South Carolina
city: McAllen
country: United States
facility: Futuro Clinical Trials, LLC.
state: Texas
city: Salt Lake City
country: United States
facility: JBR Clinical Research
state: Utah
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei City
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei City
country: Taiwan
facility: Taipei Municipal Wanfang Hospital
Study officials:
affiliation: Taiwan Liposome Company
name: Terry Tai, MD
role: STUDY_DIRECTOR
References: