2ccPA Study in Patients With Symptomatic Knee Osteoarthritis

NCT04229394 | Completed Phase 1 FDA Drug

• 1 other identifier: OEP-2PM102-101
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

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.

Conditions

Osteoarthritis (OA) of the Knee

Keywords

2ccPA

Outcome Measures

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

  85 days

Secondary Outcomes (20)

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

  85 days

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

  85 days

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

  85 days

• Maximum plasma concentration (Cmax) of 2ccPA

  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.

• Time to maximum plasma concentration (Tmax) of 2ccPA

  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.

Study Arms (2)

2ccPA

EXPERIMENTAL

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

PLACEBO COMPARATOR

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

Drug: placebo

Interventions

2ccPA 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

Also known as: 2-carba-cyclic phosphatidic acid

2ccPA

placebo 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

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Orient Europharma Co., Ltd.: lead

Study Sites (5)

Veteran General Hospital Taipei

Taipei, 112, Taiwan

Location

Tri-Service General Hospital

Taipei, 114, Taiwan

Location

Mackay Memorial Hospital

Taipei, 25160, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Taipei, 833, Taiwan

Location

National Cheng Kung University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Osteoarthritis

Interventions

2-carba-cyclic phosphatidic acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Hsiang-Cheng Chen, PHD

  Tri-Service General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The subjects and study site personnel (other than the study site pharmacists) are all blinded to the treatment assignment. An un-blind pharmacist is necessary for study drug preparation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: January 18, 2020
• Study Start: February 13, 2018
• Primary Completion: March 22, 2021
• Study Completion: March 22, 2021
• Last Updated: April 30, 2021

Record last verified: 2021-04

Locations

TW (5)