A Study to Assess Safety and Tolerability of PCRX-201 in Subjects With Painful Osteoarthritis of the Knee

August 21, 2026 updated by: Pacira Pharmaceuticals, Inc

A Phase 2, Two-Part, Randomized, Double-Blind, Active-Controlled Study to Assess the Safety and Tolerability of Enekinragene Inzadenovec (PCRX-201) in Subjects With Painful Osteoarthritis of the Knee

The goal of this clinical trial is to learn if a single knee injection of different doses (Dose A and Dose B) of an investigation product PCRX-201, following steroid pretreatment, is safe and tolerable in male of female patients 45 to 80 years old with osteoarthritis of the knee. It will also learn how the body reacts to the PCRX-201 injection and how effective the treatment is.

Researchers will compare Dose A and Dose B of PCRX-201 versus placebo from Week 1 through Week 52 to assess adverse events. Researchers will also explore how PCRX-201 may impact knee pain and joint function over time.

Participants will be asked to

  • Visit the clinic for pretreatment and drug administration

  • Visit the clinic for checkups and tests:

    1. Screening through Week 52: intially weekly, bi-weekly, later monthly
    2. Week 53 through Week 260 (Year 5): 8 visits throughout the period

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study will consist of two parts, Part A and Part B, which will use PCRX-201 from two different manufacturing processes. A total of 135 eligible subjects, with painful OA of the index knee will be enrolled. Subjects will be randomly assigned to a treatment dose group, stratified by Kellgren-Lawrence (K-L) Grade, in both parts of the study. Enrollment of subjects with K-L Grade 4 will be capped at 4 subjects per dose group in Part A and 8 subjects per dose group in Part B.

Enrollment of subjects with K-L Grade 2 or 3 will include a minimum of 4 subjects per Grade per dose group in Part A and a minimum of 8 subjects per Grade per dose group in Part B. This study does not require an equal number of subjects between K-L Grade 2 and 3. All eligible subjects will be pretreated with the same dose of methylprednisolone acetate (40 mg) on Day 1 immediately before treatment with PCRX-201 or placebo.

Part A will enroll approximately 45 subjects into 3 dose groups (15 subjects in each treatment group, stratified by K-L Grade as noted above).

Part B will enroll approximately 90 subjects into 3 groups (30 subjects in each treatment group, stratified by K-L Grade as noted above). Enrollment in Part B is dependent upon the availability of study drug developed with manufacturing process 2.

Study Type

Interventional

Enrollment (Estimated)

135

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35235
        • Withdrawn
        • Alabama Clinical Therapeutics, LLC
      • Birmingham, Alabama, United States, 35205
        • Not yet recruiting
        • Flourish Research - Birmingham
        • Principal Investigator:
          • Kenneth Jaffe
        • Contact:
    • Arizona
      • Phoenix, Arizona, United States, 85018
        • Not yet recruiting
        • OrthoArizona
        • Contact:
        • Principal Investigator:
          • Kipling Sharpe
      • Phoenix, Arizona, United States, 85032
        • Not yet recruiting
        • AARA Clinical Research - Arizona Arthritis & Rheumatology Associates - Phoenix
        • Contact:
        • Principal Investigator:
          • Eric Peters
    • California
      • Beverly Hills, California, United States, 90211
        • Active, not recruiting
        • Osteoporosis Medical Center
      • Chula Vista, California, United States, 91910
        • Not yet recruiting
        • Advanced Clinical Research Center, LLC dba TriWest Research Associates, LLC
        • Principal Investigator:
          • Arthur Mabaquiao
        • Contact:
      • Covina, California, United States, 91722
        • Not yet recruiting
        • Medvin Clinical Research - Covina
        • Principal Investigator:
          • Samy Metyas
        • Contact:
      • Huntington Beach, California, United States, 92647
        • Recruiting
        • Beach Physicians Medical Group Inc.
        • Principal Investigator:
          • Bassil Aish
        • Contact:
      • La Mesa, California, United States, 91942
        • Active, not recruiting
        • Horizon Clinical Research
      • Santa Monica, California, United States, 90403
      • West Hills, California, United States, 91307
        • Withdrawn
        • Alliance Clinical West Hills (Focus Clinical Research)
      • Whittier, California, United States, 90602
        • Not yet recruiting
        • Medvin Clinical Research - Whittier
        • Principal Investigator:
          • Tien-I Karleen Su
    • Florida
      • Daytona Beach, Florida, United States, 32117
        • Recruiting
        • Arrow Clinical Trials
        • Principal Investigator:
          • David Billmeier
        • Contact:
      • Oldsmar, Florida, United States, 34677-4681
        • Active, not recruiting
        • Journey Research Inc.
      • Plantation, Florida, United States, 33317
      • Sarasota, Florida, United States, 34232
        • Not yet recruiting
        • Gulfcoast Research Institute
        • Contact:
        • Principal Investigator:
          • Edward Stolarski
      • West Palm Beach, Florida, United States, 33409
        • Active, not recruiting
        • Palm Beach Research Center
      • Winter Park, Florida, United States, 32789
        • Active, not recruiting
        • Conquest Research
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Not yet recruiting
        • Pinnacle Trials, Inc.
        • Contact:
        • Principal Investigator:
          • Francisco Chevres
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Not yet recruiting
        • Rush Medical College - Division of Rheumatology
        • Principal Investigator:
          • Joel Block
        • Contact:
    • Louisiana
      • Lake Charles, Louisiana, United States, 70605
        • Not yet recruiting
        • Accurate Clinical Research, Inc. - Lake Charles
        • Principal Investigator:
          • Enrique Mendez
      • New Orleans, Louisiana, United States, 70115
        • Not yet recruiting
        • Best Clinical Trials, LLC
        • Contact:
        • Principal Investigator:
          • Neil Duplantier
    • Maryland
      • Baltimore, Maryland, United States, 21215
    • Michigan
      • Rochester Hills, Michigan, United States, 48307
        • Not yet recruiting
        • Michigan Orthopaedic and Spine Surgeons
        • Contact:
        • Principal Investigator:
          • Nathan Rimmke
    • Nebraska
      • Lincoln, Nebraska, United States, 68516
        • Recruiting
        • Physicians Research Collaboration
        • Principal Investigator:
          • Melvin Churchill
        • Contact:
    • Nevada
      • Las Vegas, Nevada, United States, 89109
        • Active, not recruiting
        • Excel Clinical Research
    • New York
      • Brooklyn, New York, United States, 11235-3919
        • Not yet recruiting
        • NY Scientific
        • Contact:
        • Principal Investigator:
          • Alexander Brun
      • New York, New York, United States, 10016
        • Not yet recruiting
        • New York University (NYU) Center for Musculoskeletal Care
        • Contact:
        • Principal Investigator:
          • Jonathan Samuels
    • North Carolina
      • Morehead City, North Carolina, United States, 28557
      • Wilmington, North Carolina, United States, 28412
        • Not yet recruiting
        • M3 Wake Research - Wilmington, NC
        • Principal Investigator:
          • Jeremy Hoff
    • Ohio
      • Dayton, Ohio, United States, 45432
        • Not yet recruiting
        • META Medical Research Institute
        • Principal Investigator:
          • Priyesh Mehta
        • Contact:
    • Pennsylvania
      • Altoona, Pennsylvania, United States, 16602-4472
        • Not yet recruiting
        • University Orthopedics Center
        • Principal Investigator:
          • Thomas Ellis
        • Contact:
      • Duncansville, Pennsylvania, United States, 16635
        • Active, not recruiting
        • Altoona Center For Clinical Research
    • South Carolina
      • Charleston, South Carolina, United States, 29406
        • Active, not recruiting
        • Clinical Trials of South Carolina - Charleston
      • Columbia, South Carolina, United States, 29206
        • Active, not recruiting
        • Clinical Trials of South Carolina - Columbia
    • Tennessee
      • Collierville, Tennessee, United States, 38017
    • Texas
      • Dallas, Texas, United States, 75230
        • Active, not recruiting
        • Zenos Clinical Research
      • Dallas, Texas, United States, 75231
      • Houston, Texas, United States, 77034
        • Not yet recruiting
        • Accurate Clinical Research, Inc - Houston
        • Principal Investigator:
          • Philip Waller
      • Lewisville, Texas, United States, 75057
        • Active, not recruiting
        • Epic Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subjects must be willing and able to comply with the study procedures and visit schedule and able to follow verbal and written instructions.
  • Subjects must be male or female and 45 to 80 years old, inclusive, at Screening.
  • Subjects must exhibit symptoms associated with osteoarthritis of the index knee for ≥12 months before Screening (subject self-reporting is acceptable).
  • Subjects must have index knee pain for >15 days over the last month before Screening (subject self-reporting is acceptable).
  • Subjects must have received 2 or more failed 2 or more therapies: Restricted physical activity as per Osteoarthritis Research Society International (OARSI) core level recommendation, ie, "structured land-based exercise" (this may include physical therapy), and failure of an additional type of conservative therapy for OA of the index knee, eg, nonselective NSAIDs or COX-2 inhibitors, in the past 12 months.
  • Subjects must have a body mass index (BMI) ≤40 kg/m2 at Screening.
  • Subjects must have an index knee examination indicating the index knee and the intended injection site area are free of any signs of local or joint infection at Baseline.
  • Subjects must have an index knee Average Daily Knee Pain (NRS) between ≥5.0 and ≤9.0 at Screening and Baseline.
  • Sexually active subjects of child-bearing potential (SOCBP) and their partners must agree to use effective birth control while in the study
  • Subjects must have active synovitis in the index knee as determined by ultrasound Doppler (Part A only) For Part B, participants must have active synovitis in the index knee as determined by contrast-enhanced MRI.

  • Subjects must exhibit American College of Rheumatology Criteria (clinical and radiological) for osteoarthritis as follows:

    1. Knee pain
    2. At least 1 of the following:

    i. Age >50 years ii. Morning stiffness <30 minutes iii. Crepitus on knee motion c. Osteophytes

  • Subjects must have K-L Grade 2, 3, or 4 (Part A) or K-L Grade 2 or 3 (Part B) in the index knee based on X-rays performed during Screening and confirmed by trained radiographers at a central facility before enrollment
  • Subjects need to show the presence of moderate or severe synovitis based on 11-point synovitis score using contrast-enhanced MRI (Part A). For Part B, participants need to show the presence of synovitis ≥5 on the Guermazi synovitis scoring scale using contrast-enhanced MRI to be enrolled.

Exclusion Criteria:

  • Subjects have any current or prior diagnosis of autoimmune connective tissue disorders, secondary OA conditions, benign synovial tumors, gout/pseudogout, reactive arthritis, RA, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease.
  • Subjects have any active systemic or local infection, including infection of the index knee
  • Subjects are unable to undergo MRI with contrast MRI
  • Subjects with X-ray or MRI exclusionary events
  • Subjects have an unstable index knee joint (eg, torn anterior cruciate ligament) within 12 months of Screening
  • Subjects have used any approved or investigational IA drug/biologic in index knee within 6 months of Screening (eg, hyaluronic acid, platelet rich plasma, stem cells, prolotherapy, and amniotic fluid injection)
  • Subjects are receiving or have received any gene therapy treatment (eg, IL-1Ra) in the past 3 years
  • Subjects have used IA steroids ≤3 months before screening
  • For Part B, subjects with any surgery related tot he index knee.

Other protocol-defined criteria apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Placebo Comparator: Part B Placebo
Biological: Placebo
Placebo injection
Experimental: Part A Dose A
Single Intra-Articular injection
Biological: Enekinragene Inzadenovec (PCRX-201)
Enekinragene Inzadenovec (PCRX-201) injection
Placebo Comparator: Part A, Placebo
Single Intra-Articular injection
Biological: Placebo
Placebo injection
Experimental: Part B Dose A
Single Intra-Articular injection
Biological: Enekinragene Inzadenovec (PCRX-201)
Enekinragene Inzadenovec (PCRX-201) injection
Experimental: Part B Dose B
Single Intra-Articular injection
Biological: Enekinragene Inzadenovec (PCRX-201)
Enekinragene Inzadenovec (PCRX-201) injection
Experimental: Part A, Dose B
Single Intra-Articular injection
Biological: Enekinragene Inzadenovec (PCRX-201)
Enekinragene Inzadenovec (PCRX-201) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence (number and percent) of treatment-emergent adverse events (TEAEs) for PCRX-201 Dose A and Dose B versus placebo from Week 1 through Week 52
Time Frame: Week 1 through Week 52.
Week 1 through Week 52.
Incidence (number and percent) of adverse events of special interest (AESIs) for PCRX-201 Dose A and Dose B versus placebo from Week 1 through Week 52
Time Frame: Week 1 through Week 52.
Week 1 through Week 52.
Incidence (number and percent) of serious adverse events (SAEs) for PCRX-201 Dose A and Dose B versus placebo from Week 1 through Week 52
Time Frame: Week 1 through Week 52.
Week 1 through Week 52.

Secondary Outcome Measures

Outcome Measure
Time Frame
Real-time quantitative polymerase chain reaction (qPCR) measurement profile in plasma of PCRX-201 Dose A and Dose B from postdose through Week 8
Time Frame: Days 1, 4, Weeks 2, 4, 8
Days 1, 4, Weeks 2, 4, 8
Real-time qPCR measurement profile of skin swab samples from Baseline through Week 4.
Time Frame: Days 1, 4, Weeks 2, 4
Days 1, 4, Weeks 2, 4
Assessment of the levels of neutralizing antibodies (NAbs), high-sensitivity C-reactive protein (hs-CRP), and biomarkers of inflammation (eg, interleukin [IL]- 1, cytokines [tumor necrosis factor alpha (TNFα), IL-1β, IL-6, IL-10], and chemokines [IL-8])
Time Frame: Days 1, 4, Weeks 2, 3, 4,12, 16, 24, 38
Days 1, 4, Weeks 2, 3, 4,12, 16, 24, 38
Absolute change from baseline in Average Daily Knee Pain (Numerical Rating Scale [NRS]) for PCRX-201 Dose A and Dose B versus placebo.
Time Frame: Weeks 38 and 52
Weeks 38 and 52
Absolute change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score for PCRX-201 Dose A and Dose B versus placebo.
Time Frame: Weeks 38 and 52
Weeks 38 and 52
Absolute change from baseline in WOMAC Stiffness Score for PCRX-201 Dose A and Dose B versus placebo.
Time Frame: Weeks 38 and 52
Weeks 38 and 52
Absolute change from baseline in WOMAC Physical Function Score for PCRX-201 Dose A and Dose B versus placebo.
Time Frame: Weeks 38 and 52
Weeks 38 and 52
Absolute change from Baseline on the Knee Injury and Osteoarthritis Outcome Score (KOOS) function/daily living score for PCRX-201 Dose A and Dose B versus placebo at Weeks 38 and 52.
Time Frame: Weeks 38 and 52
Weeks 38 and 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pacira Pharmaceuticals, Inc

Investigators

  • Study Director: Warrren Rizzo, MD, Pacira Pharmaceuticals, Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 26, 2025

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

July 1, 2032

Study Registration Dates

First Submitted

March 13, 2025

First Submitted That Met QC Criteria

March 13, 2025

First Posted (Actual)

March 19, 2025

Study Record Updates

Last Update Posted (Actual)

August 25, 2026

Last Update Submitted That Met QC Criteria

August 21, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201-C-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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