Study to Assess the Safety of Repeat Administration of FX006 Administered to Patients With Osteoarthritis of the Knee

An Open-label Study to Assess the Safety of Repeat Administration of FX006 to Patients With Osteoarthritis of the Knee

This is an Open-label Study to Assess the Safety of Repeat Dose of FX006 Administered to Patients with Osteoarthritis (OA) of the Knee

Study Overview

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

Detailed Description

This study is an open-label, repeat administration design of 32 mg FX006. The study will be conducted in male and female patients ≥ 40 years of age with symptomatic OA of the knee.

Eligible patients will be offered participation to receive an initial intra-articular (IA) injection of FX006 administered to the index knee at Day 1.

Patients who receive an initial injection of FX006 will return at Weeks 4 and 8 before being evaluated at 12, 16, 20 and 24 weeks for repeat administration. At the first evaluation where the patient has been determined to meet repeat administration eligibility criteria, the patient will be eligible to receive a second IA injection of FX006.

Patients who are eligible to receive a second injection will be evaluated for a total of 52 weeks post initial injection at: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52, regardless of the time at which they receive their second injection. In addition, X-rays will be completed at Screening and Week 52 or End of Study (EOS) for assessment of safety.

Patients that do not benefit from the initial treatment as determined by evaluation at Week 12 will complete the study at the Week 12 follow-up visit.

Patients who are not eligible for a second injection of FX006 after evaluation at Weeks 12, 16, 20, and 24 will complete the study at the Week 24 follow-up visit.

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Tucson Orthopedic
  • California
    • Anaheim, California, United States, 92801
      • Dream Team Clinical Research
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • Torrance, California, United States, 90509
      • Harbor-UCLA Medical Center
  • Florida
    • Clearwater, Florida, United States, 37761
      • Tampa Bay Medical Research
    • Gulf Breeze, Florida, United States, 32561
      • The Andrews Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Sports Medicine Institute
  • Massachusetts
    • Chestnut Hill, Massachusetts, United States, 02467
      • Brigham and Women's Hospital
    • Dedham, Massachusetts, United States, 02026
      • New England Baptist Hospital
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research
  • North Carolina
    • Durham, North Carolina, United States, 27701
      • Duke University
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37938
      • PMG Research of Knoxville

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Written consent to participate in the study
• 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
• Symptoms associated with OA of the index knee for ≥ 6 months prior to Screening
• Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA
• Kellgren-Lawrence (KL) Grade 2, 3 or 4 in the index knee based on X-ray performed during Screening
• Qualifying score for WOMAC A at Screening and Day 1/Baseline
• Index knee pain for >15 days over the last month (as reported by the patient)
• Body mass index (BMI) ≤ 40 kg/m2
• Ambulatory and in good general health
• Willingness to abstain from use of protocol-restricted medications during the study

Exclusion Criteria:

• Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease
• History of infection in the index knee joint
• Clinical signs and symptoms of active knee infection or crystal disease of the index knee within 1 month of Screening
• Presence of surgical hardware or other foreign body in the index knee
• Unstable index knee joint (such as a torn anterior cruciate ligament) within 12 months of Screening
• IA corticosteroid (investigational or marketed) in index knee within 3 months of Screening
• IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening
• IV or intramuscular (IM) corticosteroids (investigational or marketed) within 3 months of Screening
• Oral corticosteroids (investigational or marketed) within 1 month of Screening
• Any other IA drug/biologic use within 6 months of Screening or 5 half-lives (whichever is longer) (e.g., platelet rich plasma (PRP) injection, stem cells, prolotherapy and amniotic fluid injection)
• Prior administration 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FX006 32 mg; Single intra-articular injection	Drug: FX006 32 mg; Single intra-articular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of Treatment Emergent Adverse Events (TEAEs) in Patients With Symptomatic Osteoarthritis (OA) of the Knee Who Received Two Doses of 32 mg FX006	Analyses of adverse events (AE) were performed for events considered treatment-emergent (TE) in patients who received two doses of 32 mg FX006. TE was defined as any AE with onset after administration of the 1st dose of study drug or any event present at baseline but worsened in intensity through the study. Severity was graded by the PI using the Common Terminology Criteria for AEs Version 4.0. Grading went from Grade 1 (Mild) to Grade 5 (Death Related to AE).	Up to 52 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain 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. WOMAC A is the independent sub-scale for pain that is comprised of 5 questions. WOMAC A was administered at each visit from screening through Week 52/EOS.	12 Weeks Post Each FX006 Administration
WOMAC B Stiffness 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. WOMAC B is the independent sub-scale for stiffness that is comprised of 2 questions. WOMAC B was administered at each visit from screening through Week 52/EOS.	12 Weeks Post Each FX006 Administration
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. WOMAC C is the independent sub-scale for function that is comprised of 17 questions. WOMAC C was administered at each visit from screening through Week 52/EOS.	12 Weeks Post Each FX006 Administration
Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale	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 sub-scales: KOOS Pain, KOOS Symptoms, Function in daily living, Function in Sport and Recreation, and knee-related Quality of Life (KOOS QOL). Only KOOS QOL sub-scale (Q1-Q4) was used in this study. A Likert scale is used and all items have five possible answer options scored from 0 (No Problem) 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. Higher scores indicate a better quality of life. KOOS was administered at study visits from BL/Day 1 through week 52.	Up to 12 Weeks Post Each FX006 Administration

Collaborators and Investigators

• Sponsor: Pacira Pharmaceuticals, Inc
• Investigators: Study Director: Scott Kelley, MD, Flexion Therapeutics

Publications and helpful links

General Publications

• Spitzer AI, Richmond JC, Kraus VB, Gomoll A, Jones DG, Huffman KM, Peterfy C, Cinar A, Lufkin J, Kelley SD. Safety and Efficacy of Repeat Administration of Triamcinolone Acetonide Extended-release in Osteoarthritis of the Knee: A Phase 3b, Open-label Study. Rheumatol Ther. 2019 Mar;6(1):109-124. doi: 10.1007/s40744-019-0140-z. Epub 2019 Feb 11.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2017
• Primary Completion (Actual): July 19, 2018
• Study Completion (Actual): July 19, 2018

Study Registration Dates

• First Submitted: February 6, 2017
• First Submitted That Met QC Criteria: February 6, 2017
• First Posted (Estimated): February 8, 2017

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; Steroid; Intra-articular; Injection
• 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: FX006-2016-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No