Study of FX006 vs Normal Saline in Patients With Osteoarthritis of the Knee

A Double-Blind, Randomized, Parallel Group, Dose-Ranging Study to Assess the Safety and Efficacy of FX006 for the Treatment of Pain in Patients With Osteoarthritis of the Knee

The purpose of this study was to assess the magnitude and duration of pain relief of a single IA injection of 2 doses (16 and 32 mg) of FX006, an extended-release formulation of TCA, relative to normal saline (placebo control).

Study Overview

• Status: Completed
• Conditions: Osteoarthritis of the Knee
• Intervention / Treatment: Drug: Placebo; Drug: FX006 32 mg; Drug: FX006 16 mg

Detailed Description

This was a double-blind, randomized, parallel group, dose-ranging, single-dose study. The study was conducted in male and female patients ≥40 years of age with OA of the knee.

Approximately 300 patients with OA of the knee were randomized, using a centralized randomization procedure, to 1 of 3 treatment groups (1:1:1) and treated with a single IA injection of:

• 16 mg FX006,
• 32 mg FX006, or
• normal saline (placebo).

Each patient was evaluated for a total of 24 weeks following a single IA injection. Following screening, safety and efficacy were evaluated at 7 out-patient visits (Days 1 [Baseline], Weeks 4, 8, 12, 16, 20, and 24).

The study was expected to enroll over approximately 6 to 7 months.

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada
  • Ontario
    • Kitchener, Ontario, Canada
    • Sarnia, Ontario, Canada
    • Toronto, Ontario, Canada
    • Windsor, Ontario, Canada
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
    • Birmingham, Alabama, United States, 35216
    • Mobile, Alabama, United States, 36608
  • Arizona
    • Phoenix, Arizona, United States, 85023
    • Tucson, Arizona, United States, 85704
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
  • California
    • Anaheim, California, United States, 92801
    • Canoga Park, California, United States, 91303
    • El Cajon, California, United States, 92020
    • Los Angeles, California, United States, 90036
    • North Hollywood, California, United States, 91606
    • San Diego, California, United States, 92103
  • Connecticut
    • Stamford, Connecticut, United States, 06905
  • Florida
    • DeLand, Florida, United States, 32720
    • Fort Lauderdale, Florida, United States, 33316
    • Orlando, Florida, United States, 32825
    • Pinellas Park, Florida, United States, 33781
    • Tampa, Florida, United States, 33613
  • Georgia
    • Marietta, Georgia, United States, 30060
  • Indiana
    • Evansville, Indiana, United States, 47713
  • Kentucky
    • Paducah, Kentucky, United States, 42003
  • Maryland
    • Wheaton, Maryland, United States, 20902
  • Massachusetts
    • New Bedford, Massachusetts, United States, 02740
  • Michigan
    • Troy, Michigan, United States, 48085
  • Missouri
    • Kansas City, Missouri, United States, 64114
  • Nevada
    • Las Vegas, Nevada, United States, 89106
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
  • New York
    • New York, New York, United States, 10018
    • Rochester, New York, United States, 14609
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
    • Duncansville, Pennsylvania, United States, 16635
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
  • Texas
    • Dallas, Texas, United States, 75231
    • Houston, Texas, United States, 77055
    • San Antonio, Texas, United States, 78258
    • Victoria, Texas, United States, 77901
  • Virginia
    • Danville, Virginia, United States, 24541

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

• Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions
• Male or female >=40 years of age
• Has documented diagnosis of OA of the index knee made at least 6 months prior to Screening
• Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA
• Kellgren-Lawrence (K-L) Grade 2 or 3 in the index knee per Screening X-ray
• Qualifying mean score on the 24-h average pain score (0-10 numeric rating scale)
• Body mass index (BMI) ≤ 40 kg/m2
• Willingness to abstain from use of restricted medications

Main Exclusion Criteria:

• Ipsilateral hip OA
• Fibromyalgia, chronic pain syndrome or other concurrent medical or arthritic conditions which could interfere with the evaluation of the index knee
• History of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis or amyloidosis
• History of arthritides due to crystals (e.g., gout, pseudogout)
• History or clinical signs and symptoms of infection in the index joint
• Knee pain that is not clinically attributable to OA of the knee (e.g., radicular low back pain and hip pain that is referred to the knee that could cause misclassification)
• Pain in any other area of the lower extremities or back that is equal to or greater than the index knee pain
• IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening
• IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening
• Intramuscular (IM) corticosteroids (investigational or marketed) within 3 months of Screening
• Oral corticosteroids (investigational or marketed) within 1 month of Screening
• Inhaled, intranasal and topical corticosteroids (investigational or marketed) within 2 weeks of Screening
• Any other IA investigational drug/biologic within 6 months of Screening
• Prior use of FX006
• Women of child-bearing potential not using effective contraception or who are pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FX006 16 mg; Single 5 mL intra-articular (IA) injection Extended-release formulation	Drug: FX006 16 mg; Single 5 mL IA injection
Experimental: FX006 32 mg; Single 5 mL intra-articular (IA) injection Extended-release formulation	Drug: FX006 32 mg; Single 5 mL IA injection; Other Names: Zilretta
Placebo Comparator: Placebo; Normal Saline Single 5 mL intra-articular (IA) injection	Drug: Placebo; Single 5 mL IA injection; Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 in the Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores for 32 mg FX006 Versus Placebo	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain"and 10 indicates "pain as bad as you can imagine."	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 for WOMAC C (Function Subscale)	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline and Week 12
Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC)	The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.	Baseline and Week 12
Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."	Baseline and Weeks 16, 20 and 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC)	The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.	Baseline and Week 12
Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria	Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International. (OMERACT-OARSI) Responders are defined as participants with high improvement in pain or function.	Weeks 4, 8 and 12
Change From Baseline to Week 12 for WOMAC C (Function Subscale)	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5- point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline and Week 12
Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."Weeks 12, 16, 20, and 24 are specified as the primary and secondary endpoints for the 32 mg group and the placebo group	Baseline and Up to Week 24
Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline and Weeks 4, 8, 16, 20 and 24 (Week 12 data is represented in the secondary outcome measure)
Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline and Weeks 4, 8, 12, 16, 20 and 24
Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC	The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.	Baseline and Weeks 4, 8, 16, 20, and 24 (Week 12 data reported in secondary outcome measure)
Proportion of Patients Experiencing a >20%, 30% and 50% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Week 12	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."	12 weeks
Time to Onset of Pain Relief	Time to onset of pain relief in days is defined as the time from administration of study treatment to the first pain assessment showing >30% improvement from the weekly average daily pain score at baseline.	Baseline up to 24 Weeks after administration of study treatment

Collaborators and Investigators

• Sponsor: Pacira Pharmaceuticals, Inc
• Investigators: Study Director: Neil Bodick, MD, Flexion Therapeutics

Publications and helpful links

General Publications

• Conaghan PG, Cohen SB, Berenbaum F, Lufkin J, Johnson JR, Bodick N. Brief Report: A Phase IIb Trial of a Novel Extended-Release Microsphere Formulation of Triamcinolone Acetonide for Intraarticular Injection in Knee Osteoarthritis. Arthritis Rheumatol. 2018 Feb;70(2):204-211. doi: 10.1002/art.40364. Epub 2017 Dec 20.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: April 15, 2014
• First Submitted That Met QC Criteria: April 15, 2014
• First Posted (Estimated): April 17, 2014

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: osteoarthritis; pain; knee; corticosteroid; injection; intra-articular
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; FX006
• Other Study ID Numbers: FX006-2014-006