A Study to Evaluate the Safety and Efficacy of 2ccPA in Patients With Symptomatic Knee Osteoarthritis

NCT05807529 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: OEP-2PM102-201
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II study aims to evaluate the safety of single doses of 2ccPA 4,800 μg and 7,200 μg (Phase I), as well as the safety and efficacy of multiple doses of 2ccPA (Phase II) in patients with osteoarthritis (OA) of the knee.

Conditions

Osteoarthritis, Knee

Outcome Measures

Primary Outcomes (3)

• To define maximum tolerated dose (MTD) following the intra-articular (IA) administration of a single ascending dose (SAD) 2ccPA in patients with osteoarthritis of the knee.

  85 Days

• To evaluate the safety of 2ccPA including incidence of adverse events (AEs) and serious adverse events (SAEs).

  85 Days

• To evaluate the efficacy of multiple doses of 2ccPA vs placebo in terms of changes in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) on Day 85

  The Western Ontario and McMaster Universities Osteoarthritis (WOMAC) is a widely-used, proprietary outcome measurement tool used to evaluate the condition of subjects with Osteoarthritis (OA) of the knee and hip, including pain (5 questions), stiffness (2 questions) and physical functioning (17 questions) of the joints. Each question is scored on a scale of 0-4, which corresponds to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4).

  85 Days

Secondary Outcomes (10)

• To evaluate the efficacy of 2ccPA vs placebo in terms of changes in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) on Day 15, 29, 57 and 168

  85 Days

• To evaluate the efficacy of 2ccPA vs placebo in terms of proportion of subjects with a 20% (WOMAC20), 50% (WOMAC50), and 70% (WOMAC70) improvement in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) on Days 15, 29, 57, 85 and 168

  168 Days

• To evaluate the efficacy of 2ccPA vs placebo in terms of pain assessed by Numeric Rating Scale (NRS) on Days 15, 29, 57, 85 and 168.

  168 Days

• To evaluate the efficacy of 2ccPA vs placebo in terms of changes in Joint Space Narrowing (JSN) measured by x-ray on Day 168

  168 Days

• Maximum plasma concentration (Cmax) of 2ccPA

  168 Days

Study Arms (2)

2ccPA

EXPERIMENTAL

IP name: 2-carba-cyclic phosphatidic acid (2ccPA)

Drug: 2ccPA

placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

2ccPA DRUG

2-carba-cyclic phosphatidic acid (2ccPA) is a first-in-class phospholipase autotaxin (ATX) inhibitor that may act as a disease-modifying drug and may relieve OA associated symptoms. Phase I: 2 dose cohorts (4800μg, 7200μg) single dose at Day 1 Phase II: 3 dose cohorts (2400μg, 4800μg, 7200μg) multiple dose at Day 1, 15, 29

Also known as: 2-carba-cyclic phosphatidic acid

2ccPA

Placebo DRUG

Phase I: 2 dose cohorts (4800μg, 7200μg) single dose at Day 1 Phase II: 3 dose cohorts (2400μg, 4800μg, 7200μg) multiple dose at Day 1, 15, 29

placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent from any patient capable of giving consent.
• Male or female patients, 40 to 80 years of age.
• Documented clinical diagnosis of symptomatic OA affecting at least one knee of a minimum of 6 months prior to screening.
• The study knee has OA of Grade 2 to 3 severity based on the Kellgren Lawrence grading scale.
• A score \> 6 and \< 16 out of 20 on the WOMAC pain subscale for the study knee.
• Pain in the study knee for most of the 30 days (i.e., more than half of the days) prior to randomization.
• Women of childbearing potential must agree to practice a medically acceptable contraceptive regimen from screening visit until at least 1 month after the study treatment and must have a negative pregnancy test no earlier than 72 hours prior to study treatment. Male subjects must agree to practice a medically acceptable contraceptive regimen (i.e., sterilization surgery, barrier method, abstention) from screening visit until at least 1 month after the study treatment.

You may not qualify if:

• Patients with known or suspected hypersensitivity to 2ccPA or any of its excipients.
• Use of intra-articular corticosteroids, hyaluronic acid, or other IA injection in the study knee within 3 months prior to study entry (randomization).
• Use of chondroitin and/or glucosamine within 4 weeks prior to study entry (randomization).
• Administered or requiring systemic or topical treatment of the study knee joint including immunosuppressive agents, anti-inflammatory drugs, steroids, or opioids for knee OA within 1 week prior to randomization. Acetaminophen (oral daily dose ≤ 3000 mg or topical use at any dose) can be taken up to 24 hours prior to randomization. For long-acting steroids (i.e., dexamethasone, betamethasone), subjects who received systemic treatment within 2 weeks before randomization will be excluded.
• History of post-traumatic knee arthritis, or evidence of intra-articular bleeding of the study knee.
• History of reiter's syndrome, gouty arthritis, systemic lupus erythematosus (SLE), sicca syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, lymphoma, arthritis associated with inflammatory bowel disease, sarcoidosis, amyloidosis or any other immune disease that based on investigators' discretion.
• Periarticular inflammation from any cause, including referred pain, bursitis, tendonitis, soft tissue tenderness or acute pain from injury.
• Subjects with clinical signs and symptoms of active knee infection or being treated for knee infection at screening.
• Arthroscopic or open surgery on the study knee within 6 months prior to study entry (randomization).
• Prior knee replacement on the study knee or planned knee replacement during the study period.
• Subjects with meniscus tears that require repairment surgery or known anterior cruciate ligament rupture.
• Subjects with known severe synovitis, synovium necrosis in the study knee joint.
• Subjects with known malignancy.
• Use of any chemotherapeutic or systemic immunosuppressant agents for inflammatory diseases within 6 months prior to study entry (randomization).
• Current use of anticoagulants, including warfarin, heparin, low molecular weight heparin, dabigatran, or factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, and betrixaban). Subject requiring routine use of low-dose aspirin for preventing thrombosis (≤ 100 mg/day) will not be excluded.

Sponsors & Collaborators

• Orient Europharma Co., Ltd.: lead

Study Sites (1)

Tri-Service General Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

2-carba-cyclic phosphatidic acid

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Hsiang-Cheng Chen

  Tri-Service General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2022
• First Posted: April 11, 2023
• Study Start: November 3, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: March 21, 2024

Record last verified: 2024-03

Locations

TW (1)