- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04229394
2ccPA Study in Patients With Symptomatic Knee Osteoarthritis
Phase I Safety, Tolerability, and Pharmacokinetics Study of 2ccPA in Patients With Symptomatic Knee Osteoarthritis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Osteoarthritis (OA) is a degenerative disease frequently associated with symptoms such as inflammation, stiffness, muscle weakness, joint swollen and joint pain. 2-carba-cyclic phosphatidic acid (2ccPA) is the derivative of natural occurring phospholipid mediator, cyclic phosphatidic acid (cPA). Previous studies suggested that 2ccPA inhibits inflammation and may relieve the pain caused by osteoarthritis.
This clinical study aims to assess the safety, tolerability, and pharmacokinetics as well as the maximal tolerated dose (MTD) of a single-dose 2ccPA in symptomatic knee OA. Safety and efficacy data for the design and conduction of subsequent studies will also be collected.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Taipei, Taiwan, 114
- Tri-Service General Hospital
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Taipei, Taiwan, 112
- Veteran General Hospital Taipei
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Taipei, Taiwan, 25160
- Mackay Memorial Hospital
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Taipei, Taiwan, 833
- Kaohsiung Chang Gung Memorial Hospital
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Taipei, Taiwan
- National Cheng Kung University Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female subjects who are aged between 40 and 75 years old (inclusive)
- Subjects diagnosed with symptomatic knee OA for at least 6 months prior to study entry (randomization)
- Subjects whose radiographic evidence of knee OA are classified as grade II or III (according to Kellgren and Lawrence grading system)
- Subjects with OA knee pain on the majority of days in the past 30 days prior to study entry (randomization).
- A score of over 8 and below 16 out of 20 for the WOMAC pain subscale in the index knee in screening
- Male subjects must agree to practice medically acceptable contraceptive regimen (i.e., sterilization surgery, barrier method, abstention) from screening visit until at least 1 month after the study treatment.
- Subjects who are willing to sign the informed consent form (ICF)
- Subjects with normal liver and renal function:
ALT and AST do not exceed 1.5 ULN (upper limit of normal) Serum Cr levels do not exceed 1.0 ULN
Exclusion Criteria:
- Subjects with known hypersensitivity to study medication
- Female subjects who are pregnant or lactating. Women of childbearing potential must agree to practice medically acceptable contraceptive regimen from screening visit until at least 1 month after the study treatment and must have a negative urine pregnancy test no earlier than 72 hours prior to study treatment.
- Intra-articular use of corticosteroid, hyaluronic acid or other intra-articular injection in study knee within 3 months prior to study entry (randomization)
- Use of chondroitin and/ or glucosamine within 4 weeks prior to study entry (randomization)
- Subjects with known malignancy
- History of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, lymphoma, arthritis associated with inflammatory bowel disease, sarcoidosis and amyloidosis
- Prior arthroscopic or open surgery on the study knee within 6 months prior to study entry (randomization)
- Clinical signs and symptoms of active knee infection or being treated for knee infection at screening
- Patients with active inflammation: patients with CRP higher than upper limit of normal range at screening visit will be excluded from the study.
- Subjects with concurrent medical or arthritic condition that could interfere with evaluation of the index knee joint, including fibromyalgia, based on investigator's clinical judgment
- More significant pain from the back or the hip than the knee
- Skin breakdown or lesion on the study knee that is not suitable for injection, based on investigator's discretion
- Prior knee replacement on the study knee or planned knee replacement during the study period
- Subjects with (1) meniscus tears which requires repairment surgery OR (2) anterior cruciate ligament rupture based on screening MRI results
- Patients with known severe synovitis, synovium necrosis in the target knee joint judged by investigator at screening
- Patients with PT/ APTT higher than the upper limit of normal range at screening
- History of drug or alcohol dependence in the past 3 years
- Having known infection with HIV-1, HBV, HCV
- Use of any investigational drug or participation in any drug study within 4 weeks prior to study entry (randomization)
- Subjects who are unwilling or unable to comply with study procedures
- Any clinical condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk to participate in the study or confounds the ability to interpret data from the study as judged by the investigator.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 2ccPA
Only day 1 Intra-articular injection can be given under direct ultrasound guidance; the only one strength for 2ccPA injection vial is 2,400 μg (1.2 mL per vial). IP name: 2-carba-cyclic phosphatidic acid (2ccPA) |
Four dose cohorts (50 μg, 200 μg, 800 μg, and 2,400 μg) are planned in this study sequentially. study group: one dose intra-articular on day1
Other Names:
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Placebo Comparator: Placebo
Only day 1 Intra-articular injection can be given under direct ultrasound guidance; placebo
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A total of 8 subjects will be recruited and randomized in each dose cohort with a 3:1 ratio (6 subjects in the 2ccPA treatment arm and 2 subjects in the placebo arm). control group: one dose intra-articular on day 1 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse events will be coded with MedDRA and analyzed by system organ class (SOC) and preferred term. The number of subjects who experience DLT will be calculated at each dose level and the result of MTD will be provided.
Time Frame: 85 days
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To determine safety and tolerability as well as the maximal tolerated dose (MTD) of a single-dose 2ccPA in symptomatic knee OA
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85 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
20% improvement in the The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and physical function subscales
Time Frame: 85 days
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Proportion of subjects with a 20% improvement in the WOMAC pain and physical function subscales on Day 2, Day 3, Day 8, Day 15, Day 29 post treatment, compared with placebo group and baseline
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85 days
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50% improvement in the The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and physical function subscales
Time Frame: 85 days
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Proportion of subjects with a 50% improvement in the WOMAC pain and physical function subscales on Day 2, Day 3, Day 8, Day 15, Day 29 post treatment, compared with placebo group and baseline
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85 days
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70% improvement in the The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and physical function subscales
Time Frame: 85 days
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Proportion of subjects with a 70% improvement in the WOMAC pain and physical function subscales on Day 2, Day 3, Day 8, Day 15, Day 29 post treatment, compared with placebo group and baseline
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85 days
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Maximum plasma concentration (Cmax) of 2ccPA
Time Frame: at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Pharmacokinetic profile of 2ccPA
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at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Time to maximum plasma concentration (Tmax) of 2ccPA
Time Frame: at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Pharmacokinetic profile of 2ccPA
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at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Area under plasma concentration-time curve (AUC) of 2ccPA
Time Frame: at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Pharmacokinetic profile of 2ccPA
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at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Apparent total body clearance (CL/F) of 2ccPA
Time Frame: at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Pharmacokinetic profile of 2ccPA
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at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Apparent volume of distribution (Vz/F) of 2ccPA
Time Frame: at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Pharmacokinetic profile of 2ccPA
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at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Elimination half-life (t1/2) of 2ccPA
Time Frame: at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Pharmacokinetic profile of 2ccPA
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at baseline (pre-dose), 15 ± 5 minutes, 30 ± 5 minutes, 1 hour ± 10 minutes, 2 hours ± 10 minutes, 4 hours ± 10 minutes, 6 hours ± 10 minutes, 8 hours ± 10 minutes, 12 ± 2 hours, 24 ± 2 hours (Day 2) and 48 ± 2 hours (Day 3) after 2ccPA treatment.
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Synovial fluid 2ccPA level
Time Frame: before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.
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Changes from baseline (pre-dose) in synovial fluid 2ccPA and synovial fluid matrix metalloproteinase (MMP)-1, -3 and -13 levels at 24 hours after 2ccPA treatment
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before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.
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Synovial fluid matrix metalloproteinase (MMP)-1 level
Time Frame: before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.
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Changes from baseline (pre-dose) in synovial fluid 2ccPA and synovial fluid matrix metalloproteinase (MMP)-1, -3 and -13 levels at 24 hours after 2ccPA treatment
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before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.
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Synovial fluid matrix metalloproteinase (MMP)-3 level
Time Frame: before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.
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Changes from baseline (pre-dose) in synovial fluid 2ccPA and synovial fluid matrix metalloproteinase (MMP)-1, -3 and -13 levels at 24 hours after 2ccPA treatment
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before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.
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Synovial fluid matrix metalloproteinase (MMP)-13 level
Time Frame: before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.
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Changes from baseline (pre-dose) in synovial fluid 2ccPA and synovial fluid matrix metalloproteinase (MMP)-1, -3 and -13 levels at 24 hours after 2ccPA treatment
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before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.
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Serum prostaglandin E2 (PGE2) level
Time Frame: at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment
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Changes from baseline (pre-dose) in serum prostaglandin E2 (PGE2) levels at 30 minutes, 1 hour, 2 hours, 4 hours, 12 hours and 24 hours after 2ccPA treatment
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at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment
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Serum matrix metalloproteinase (MMP)-1 level
Time Frame: at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment
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Changes from baseline (pre-dose) in serum matrix metalloproteinase (MMP)-1,at 30 minutes, 1 hour, 2 hours, 4 hours, 12 hours and 24 hours after 2ccPA treatment
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at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment
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Serum matrix metalloproteinase (MMP)-3 levels
Time Frame: at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment
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Changes from baseline (pre-dose) in serum matrix metalloproteinase (MMP)-3,at 30 minutes, 1 hour, 2 hours, 4 hours, 12 hours and 24 hours after 2ccPA treatment
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at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment
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Serum matrix metalloproteinase (MMP)-13 level
Time Frame: at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment
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Changes from baseline (pre-dose) in serum matrix metalloproteinase (MMP)-13,at 30 minutes, 1 hour, 2 hours, 4 hours, 12 hours and 24 hours after 2ccPA treatment
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at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment
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Plasma concentration of 2ccPA
Time Frame: at pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours and 48 hours after 2ccPA treatment
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Plasma concentration of 2ccPA at pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours and 48 hours after 2ccPA treatment
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at pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours and 48 hours after 2ccPA treatment
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Joint space narrowing
Time Frame: 85 days
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To investigate joint space narrowing by MRI at Day 85, compared with baseline and the placebo group
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85 days
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Ectopic bone formation
Time Frame: 85 days
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To investigate ectopic bone formation by MRI at Day 85, compared with baseline and the placebo group
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85 days
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Hsiang-Cheng Chen, PHD, Tri-Service General Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- OEP-2PM102-101
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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