2ccPA Study in Patients With Symptomatic Knee Osteoarthritis

NCT ID: NCT04229394

Last Updated: 2021-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-13
• Study Completion Date: 2021-03-22

Brief 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.

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.

Conditions

Osteoarthritis (OA) of the Knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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)

Group Type: EXPERIMENTAL

2ccPA

Intervention Type: DRUG

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

placebo

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

Intervention Type: DRUG

Other Intervention Names

2-carba-cyclic phosphatidic acid

Eligibility Criteria

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

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Orient Europharma Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hsiang-Cheng Chen, PHD

Role: PRINCIPAL_INVESTIGATOR

Tri-Service General Hospital

Locations

Veteran General Hospital Taipei

Taipei, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Mackay Memorial Hospital

Taipei, , Taiwan

Kaohsiung Chang Gung Memorial Hospital

Taipei, , Taiwan

National Cheng Kung University Hospital

Taipei, , Taiwan

Countries

Taiwan

Other Identifiers

OEP-2PM102-101

Identifier Type: -

Identifier Source: org_study_id