Osteoarthritis of the KneePhase 2NCT03754049
A Phase 2, Open Label, Pharmacokinetic (PK) Study of TLC599 in Subjects With Osteoarthritis of the Knee
A Phase 2 study testing TLC599 and DSP in people with Osteoarthritis of the Knee, run by Taiwan Liposome Company at 10 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Osteoarthritis of the Knee
- What is being tested?
- TLC599 and DSP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 21 Jan 2019to 7 Nov 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- 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.
Who cannot join
- 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.
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- 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)
- 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
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States7 sites
Clinical Trials of South Carolina
Charleston, South Carolina, 29406
Futuro Clinical Trials, LLC.
McAllen, Texas, 78501
Panax Clinical Research
Miami, Florida, 33014
South Coast Research Center
Miami, Florida, 33136
Syneos Health
Miami, Florida, 33136
Arizona Research Center
Phoenix, Arizona, 85053
JBR Clinical Research
Salt Lake City, Utah, 84107
Taiwan3 sites
China Medical University Hospital
Taichung, 404
Tri-Service General Hospital
Taipei, 114
Taipei Municipal Wanfang Hospital
Taipei, 116
About this study
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
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.
Read the detailed description
This Phase 2, open-label, 1 period, parallel study will enroll
- 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.
- 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.
- Conditions
- Osteoarthritis of the Knee
- Being tested
- TLC599, DSP
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TLC599Drug
Also called TLC599 Injection
TLC599 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient).
DSPDrug
Also called Dexamethasone Sodium Phosphate
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.
| Study group | Role | What they receive |
|---|---|---|
| TLC599 12 mg | Experimental | 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. Receives: Drug: TLC599 |
| TLC599 6 mg | Experimental | 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. Receives: Drug: TLC599 |
| DSP 4 mg | Active comparator | 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). Receives: Drug: DSP |
| DSP 10 mg | Active comparator | 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). Receives: Drug: DSP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the Curve [AUC]
Area under the concentration-time curve
Measured: Baseline till 24 weeks post investigational product (IP) administration
Cmax: maximum concentration
Maximum concentration
Measured: Baseline till 24 weeks post IP administration
Tmax: time to peak concentration
Time to peak concentration
Measured: Baseline till 24 weeks post IP administration
Secondary outcomes (2)
Number of adverse events (AEs), including serious adverse event (SAE) and treatment-emergent AE
Number of AEs, including SAE and treatment-emergent AE
Measured: Screening till 25 weeks post IP administration
Cortisol concentration
Cortisol concentration
Measured: baseline till 24 weeks post IP administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2018
- Study start21 Jan 2019
- Primary completion7 Nov 2023
- Study completion7 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis of the KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taiwan Liposome Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Terry Tai, MD, Study director, Taiwan Liposome Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03754049
- Sponsor's protocol ID
- TLC599A2004
- Status last verified
- Oct 2024
- First submitted
- 16 Nov 2018
- Last updated
- 23 Oct 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03754049
- Acronym / sponsor ID
- TLC599A2004
- Conditions
- Osteoarthritis of the Knee
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Taiwan Liposome CompanyIndustry (pharma, biotech, devices)
- Study start
- 21 Jan 2019 (actual)
- Primary completion
- 7 Nov 2023 (actual)
- Study completion
- 7 Nov 2023 (actual)
- First posted
- 27 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TLC599 12 mg | Experimental | Drug: TLC59912 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. |
| TLC599 6 mg | Experimental | Drug: TLC5996 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. |
| DSP 4 mg | Active comparator | Drug: DSPDexamethasone 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). |
| DSP 10 mg | Active comparator | Drug: DSPDexamethasone 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
- Age 18-45, non-smokers, BMI 18.5-25 kg/m2, body weight ≥ 50.0 kg (males) or ≥ 45.0 kg (females).
Key exclusion criteria (33 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TLC599Also: TLC599 InjectionTLC599 is manufactured with the proprietary lipid formulation in lyophilized form (BioSeizer) for the reconstitution with the aqueous DSP (active ingredient). | Drug | TLC599 12 mg, TLC599 6 mg |
| DSPAlso: Dexamethasone Sodium PhosphateDexamethasone sodium phosphate (DSP) is a glucocorticoid widely used in the treatment of joint pain such as gout, osteoarthritis and rheumatoid arthritis via IA injection. | Drug | DSP 10 mg, DSP 4 mg |
Primary outcome
Area under the Curve [AUC]
Time frame: Baseline till 24 weeks post investigational product (IP) administration
Area under the concentration-time curve
Cmax: maximum concentration
Time frame: Baseline till 24 weeks post IP administration
Maximum concentration
Tmax: time to peak concentration
Time frame: Baseline till 24 weeks post IP administration
Time to peak concentration
2 secondary outcomes
Number of adverse events (AEs), including serious adverse event (SAE) and treatment-emergent AE
Time frame: Screening till 25 weeks post IP administration
Cortisol concentration
Time frame: baseline till 24 weeks post IP administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Terry Tai, MD study director
Taiwan Liposome Company
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TLC599 and DSP in people with Osteoarthritis of the Knee, run by Taiwan Liposome Company at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the Curve [AUC] (time frame: Baseline till 24 weeks post investigational product (IP) administration). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2024.