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CompletedNCT04229394Updated Apr 30, 2021

2ccPA Study in Patients With Symptomatic Knee Osteoarthritis

A Phase 1 interventional study of 2ccPA and placebo in Osteoarthritis (OA) of the Knee, sponsored by Orient Europharma Co., Ltd.. Completed at 5 sites in Taiwan. Open to participants aged 40 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-04-30.

Sponsored by Orient Europharma Co., Ltd. · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Primary completion was Mar 2021, 5 years 6 months ago, and no results have been posted to the registry.
Phase
Phase 1
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
40 Years to 75 Years
Sex
All
01

Study summary

This clinical trial is designed to determine safety and tolerability as well as the MTD of a single-dose 2ccPA and PK data in symptomatic knee OA.

Read the 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.

02

Conditions studied

  • Osteoarthritis (OA) of the Knee

Keywords

  • 2ccPA
03

In context

Osteoarthritis

4,398 studies on the registry are indexed under Osteoarthritis; 583 are open to participants now.

This study's enrollment of 40 is below the median of 70 across 3,440 interventional studies indexed under Osteoarthritis.

Browse Osteoarthritis studies →

Lead sponsor

Orient Europharma Co., Ltd. is the lead sponsor of 7 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Male or female subjects who are aged between 40 and 75 years old (inclusive)
  2. Subjects diagnosed with symptomatic knee OA for at least 6 months prior to study entry (randomization)
  3. Subjects whose radiographic evidence of knee OA are classified as grade II or III (according to Kellgren and Lawrence grading system)
  4. Subjects with OA knee pain on the majority of days in the past 30 days prior to study entry (randomization).
  5. A score of over 8 and below 16 out of 20 for the WOMAC pain subscale in the index knee in screening
  6. 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.
  7. Subjects who are willing to sign the informed consent form (ICF)
  8. 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

Exclusion Criteria:

  1. Subjects with known hypersensitivity to study medication
  2. 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.
  3. Intra-articular use of corticosteroid, hyaluronic acid or other intra-articular injection in study knee within 3 months prior to study entry (randomization)
  4. Use of chondroitin and/ or glucosamine within 4 weeks prior to study entry (randomization)
  5. Subjects with known malignancy
  6. History of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, lymphoma, arthritis associated with inflammatory bowel disease, sarcoidosis and amyloidosis
  7. Prior arthroscopic or open surgery on the study knee within 6 months prior to study entry (randomization)
  8. Clinical signs and symptoms of active knee infection or being treated for knee infection at screening
  9. Patients with active inflammation: patients with CRP higher than upper limit of normal range at screening visit will be excluded from the study.
  10. 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
  11. More significant pain from the back or the hip than the knee
  12. Skin breakdown or lesion on the study knee that is not suitable for injection, based on investigator's discretion
  13. Prior knee replacement on the study knee or planned knee replacement during the study period
  14. Subjects with (1) meniscus tears which requires repairment surgery OR (2) anterior cruciate ligament rupture based on screening MRI results
  15. Patients with known severe synovitis, synovium necrosis in the target knee joint judged by investigator at screening
  16. Patients with PT/ APTT higher than the upper limit of normal range at screening
  17. History of drug or alcohol dependence in the past 3 years
  18. Having known infection with HIV-1, HBV, HCV
  19. Use of any investigational drug or participation in any drug study within 4 weeks prior to study entry (randomization)
  20. Subjects who are unwilling or unable to comply with study procedures
  21. 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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
40 participants (actual)

Study arms

  • 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)

    Drug: 2ccPA

  • Placebo comparator
    Placebo

    Only day 1 Intra-articular injection can be given under direct ultrasound guidance; placebo

    Drug: placebo

Interventions

  • Drug2ccPA

    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

    Also known as: 2-carba-cyclic phosphatidic acid

  • Drugplacebo

    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

06

What researchers measure

Primary outcomes

  1. 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.

    To determine safety and tolerability as well as the maximal tolerated dose (MTD) of a single-dose 2ccPA in symptomatic knee OA

    Time frame: 85 days

Secondary outcomes

  1. 20% improvement in the The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and physical function subscales

    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

    Time frame: 85 days

  2. 50% improvement in the The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and physical function subscales

    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

    Time frame: 85 days

  3. 70% improvement in the The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and physical function subscales

    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

    Time frame: 85 days

  4. Maximum plasma concentration (Cmax) of 2ccPA

    Pharmacokinetic profile 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.

  5. Time to maximum plasma concentration (Tmax) of 2ccPA

    Pharmacokinetic profile 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.

  6. Area under plasma concentration-time curve (AUC) of 2ccPA

    Pharmacokinetic profile 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.

  7. Apparent total body clearance (CL/F) of 2ccPA

    Pharmacokinetic profile 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.

  8. Apparent volume of distribution (Vz/F) of 2ccPA

    Pharmacokinetic profile 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.

  9. Elimination half-life (t1/2) of 2ccPA

    Pharmacokinetic profile 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.

  10. Synovial fluid 2ccPA level

    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

    Time frame: before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.

  11. Synovial fluid matrix metalloproteinase (MMP)-1 level

    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

    Time frame: before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.

  12. Synovial fluid matrix metalloproteinase (MMP)-3 level

    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

    Time frame: before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.

  13. Synovial fluid matrix metalloproteinase (MMP)-13 level

    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

    Time frame: before intra-articular injection treatment and 24 hours ± 2 hours after intra-articular injection.

  14. Serum prostaglandin E2 (PGE2) level

    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

    Time frame: at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment

  15. Serum matrix metalloproteinase (MMP)-1 level

    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

    Time frame: at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment

  16. Serum matrix metalloproteinase (MMP)-3 levels

    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

    Time frame: at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment

  17. Serum matrix metalloproteinase (MMP)-13 level

    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

    Time frame: at 1 hour, 12 hours, 24 hours, 48 hours, Day 8 and Day 15 (PGE2 only) after 2ccPA treatment

  18. Plasma concentration of 2ccPA

    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

    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

  19. Joint space narrowing

    To investigate joint space narrowing by MRI at Day 85, compared with baseline and the placebo group

    Time frame: 85 days

  20. Ectopic bone formation

    To investigate ectopic bone formation by MRI at Day 85, compared with baseline and the placebo group

    Time frame: 85 days

07

Study locations

5 sites
  • Veteran General Hospital Taipei
    Taipei, 112, Taiwan
  • Tri-Service General Hospital
    Taipei, 114, Taiwan
  • Mackay Memorial Hospital
    Taipei, 25160, Taiwan
  • Kaohsiung Chang Gung Memorial Hospital
    Taipei, 833, Taiwan
  • National Cheng Kung University Hospital
    Taipei, Taiwan
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 30, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT04229394
Lead sponsor
Orient Europharma Co., Ltd.
Responsible party
Sponsor
First posted
Jan 18, 2020
Start date
Feb 13, 2018
Primary completion
Mar 22, 2021
Completion
Mar 22, 2021
Last update
Apr 30, 2021

Study contacts

Hsiang-Cheng Chen, PHD
principal investigator · Tri-Service General Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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