Study of FX006 for the Treatment of Pain in Patients With Osteoarthritis of the Knee

A Double-Blind, Randomized, Single-Dose 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 safety and efficacy of FX006 for the treatment of pain in patients with osteoarthritis of the knee.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis of the Knee
• Intervention / Treatment: Drug: FX006; Drug: Placebo; Drug: TCA IR 40

Detailed Description

This study was a double-blind, randomized, single dose design. The study was conducted in male and female patients ≥40 years of age with OA of the knee. Approximately 450 patients with OA of the knee were randomized to 1 of 3 treatment groups (1:1:1) and treated with a single IA injection of:

• 32 mg FX006,
• normal saline (placebo), or
• 40 mg TCA IR.

Randomization was stratified by weekly mean of the average daily (24-hour) pain intensity (ADP) scores at baseline, with the following classifications: 5 to <6, 6 to <7, and ≥7.

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 in approximately 6 months.

• Study Type: Interventional
• Enrollment (Actual): 486
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Broadmeadow, New South Wales, Australia, 02292
    • Geelong, New South Wales, Australia, 03220
    • Merewether, New South Wales, Australia, 02291
    • St. Leonards, New South Wales, Australia, 02065
  • Queensland
    • Sherwood, Queensland, Australia, 04075
  • Victoria
    • Malvern, Victoria, Australia, 03145
• Canada
  • Ontario
    • Quebec, Ontario, Canada, G1W4R4
    • Toronto, Ontario, Canada, M9V4B4
    • Windsor, Ontario, Canada, N8W1E6
• Denmark
  • Aalborg, Denmark
  • Ballerup, Denmark
  • Vejle, Denmark
• Estonia
  • Tallinn, Estonia
• Hong Kong
  • Hong Kong, Hong Kong
• Lithuania
  • Vilnius, Lithuania, 10323
• Romania
  • Bucharest, Romania, 30463
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
    • Tucson, Arizona, United States, 85712
  • California
    • Anaheim, California, United States, 92801
    • Canoga Park, California, United States, 91303
    • North Hollywood, California, United States, 91606
    • San Diego, California, United States, 92103
  • Colorado
    • Denver, Colorado, United States, 80209
  • Florida
    • Atlantis, Florida, United States, 33462
    • DeLand, Florida, United States, 32720
    • Hialeah, Florida, United States, 33012
    • Sarasota, Florida, United States, 34232
    • West Palm Beach, Florida, United States, 33409
  • Kansas
    • Prairie Village, Kansas, United States, 66206
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
  • North Carolina
    • Cary, North Carolina, United States, 27518
    • Cary, North Carolina, United States
      • PMG Research of Cary
    • Charlotte, North Carolina, United States, 28209
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
  • Tennessee
    • Knoxville, Tennessee, United States, 37912
      • PMG Research of Knoxville
    • Knoxville, Tennessee, United States, 37938
      • PMG Research of Knoxville
  • Texas
    • Dallas, Texas, United States, 75231
  • Virginia
    • Newport News, Virginia, United States, 23606

Participation Criteria

Eligibility Criteria

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

Description

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 symptoms associated with OA of the index knee for 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
• Index knee pain for > 15 days over the last month
• 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

Exclusion Criteria:

• Any condition that could possibly confound the patient's assessment of index knee pain in judgement of the investigator (i.e., iIpsilateral hip OA, gout, 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 or greater than the index knee pain)
• Fibromyalgia, Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease
• History of infection in the index knee
• Clinical signs and symptoms of active knee infection or crystal disease of the index knee within 1 month of Screening
• Unstable joint within 12 months of screening
• 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) or oral corticosteroids (investigational or marketed) within 1 month 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 32mg; Single 5 mL intra-articular (IA) injection Extended-release Formulation	Drug: FX006; Single 5 mL IA injection; Other Names: Zilretta
Placebo Comparator: Normal Saline; Single 5 mL intra-articular (IA) injection	Drug: Placebo; Single 5 mL IA injection; Other Names: Normal Saline
Active Comparator: TCA IR 40 mg; Single 1 mL intra-articular (IA) injection TCA IR 40 mg: Immediate-release formulation	Drug: TCA IR 40; Single 1 mL IA injection; Other Names: Kenalog®-40 Injection; Kenacort-A 40; Triamcinolone Acetonide Crystalline Suspension (TAcs)

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 (ADP) Intensity Scores for 32 mg FX006 Versus Placebo	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where ) indicates "no pain" and 10 indicates "pain as bad as you can imagine."	Baseline and 12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Effect Curve (AUE) of Change From Baseline in the Weekly Mean of the ADP Scores From Baseline to Week 12 for FX006 Relative to Placebo	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where ) indicates "no pain" and 10 indicates "pain as bad as you can imagine."	Baseline to 12 Weeks
AUE of Change From Baseline in Weekly Mean of the ADP Scores From Baseline to Week 12 for FX006 Relative to TCA IR	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where ) indicates "no pain" and 10 indicates "pain as bad as you can imagine."	Baseline to 12 Weeks
Change From Baseline to Week 12 in the Weekly Mean of the ADP Scores From Baseline to Week 12 for FX006 Relative to TCA IR	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where ) indicates "no pain" and 10 indicates "pain as bad as you can imagine."	Baseline through 12 Weeks
AUE of Change From Baseline in Weekly Mean of the ADP Scores From Baseline to Week 24 for FX006 Relative to Placebo	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where ) indicates "no pain" and 10 indicates "pain as bad as you can imagine."	Baseline to 24 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Each Week in Weekly Mean of the ADP Scores	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where ) indicates "no pain" and 10 indicates "pain as bad as you can imagine."	Weeks 1-11 & Weeks 13-24
Change From Baseline Over Time for WOMAC A (Pain Subscale) at Weeks 4, 8, 12, 16, 20 and 24.	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.	Weeks 4, 8, 12, 16, 20, and 24
Change From Baseline Over Time for WOMAC B (Stiffness Subscale) at Weeks 4, 8, 12, 16, 20 and 24	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.	Weeks 4, 8, 12, 16, 20 and 24
Change From Baseline Over Time for WOMAC C (Function Subscale) at Weeks 4, 8, 12, 16, 20 and 24	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.	Weeks 4, 8, 12, 16, 20 and 24
Change From Baseline Over Time for Knee Injury and Osteoarthritis Outcome Score (KOOS) Quality of Life (QOL) Subscale at Weeks 4, 8, 12 and 24	The Knee injury and Osteoarthritis Outcome Score (KOOS) is a participant (patient)-reported outcome measurement instrument, developed to assess the patient's opinion about their knee and associated problems. The KOOS evaluates both short-term and long-term consequences of knee injury and also consequences of primary osteoarthritis (OA). It holds 42 items in five separately scored subscales: KOOS Pain, KOOS Symptoms, Function in daily living (KOOS ADL), Function in Sport and Recreation (KOOS Sport/Rec), and knee-related Quality of Life (KOOS QOL). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems). Each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures. Higher scores indicate better quality of life.	Weeks 4, 8, 12, and 24
Responder Status as Defined by Proportion of Patients Experiencing >30% Decrease in Pain From Baseline in Weekly Mean of the ADP Scores at Each Week (Weeks 1-24)	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 1-24
Responder Status as Defined by Proportion of Patients Experiencing >50% Decrease in Pain From Baseline in Weekly Mean of the ADP Scores at Each Week (Weeks 1-24)		Weeks 1-24
Time to Onset of Pain Relief	Time to onset of pain relief is defined as the time from administration of study drug to the first daily pain assessment showing >30% improvement from the weekly mean of the ADP scores at baseline	Baseline to >30% improvement (measured up to 30 days)
Average Weekly and Total Consumption of Rescue Medications at Each Week (Weeks 1-24)		Weeks 1-24

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Ross E, Katz NP, Conaghan PG, Kivitz A, Turk DC, Spitzer AI, Jones DG, Lanier RK, Cinar A, Lufkin J, Kelley SD. Improved Treatment Effect of Triamcinolone Acetonide Extended-Release in Patients with Concordant Baseline Pain Scores on the Average Daily Pain and Western Ontario and McMaster Universities Osteoarthritis Index Pain Scales. Pain Ther. 2022 Mar;11(1):289-302. doi: 10.1007/s40122-021-00335-z. Epub 2021 Nov 17.
• Langworthy MJ, Conaghan PG, Ruane JJ, Kivitz AJ, Lufkin J, Cinar A, Kelley SD. Efficacy of Triamcinolone Acetonide Extended-Release in Participants with Unilateral Knee Osteoarthritis: A Post Hoc Analysis. Adv Ther. 2019 Jun;36(6):1398-1411. doi: 10.1007/s12325-019-00944-3. Epub 2019 Apr 9.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: February 3, 2015
• First Submitted That Met QC Criteria: February 5, 2015
• First Posted (Estimated): February 6, 2015

Study Record Updates

• Last Update Posted (Estimated): 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate; FX006
• Other Study ID Numbers: FX006-2014-008