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

• ClinicalTrials.gov Identifier: NCT02116972
• Recruitment Status: Completed
• First Posted: April 17, 2014
• Results First Posted: March 20, 2018
• Last Update Posted: March 20, 2018
• Sponsor: Flexion Therapeutics, Inc.
• Information provided by (Responsible Party): Flexion Therapeutics, Inc.

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Osteoarthritis of the Knee	Drug: FX006 32 mg; Drug: Placebo; Drug: FX006 16 mg	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 310 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2014
• Actual Primary Completion Date: November 2015
• Actual Study Completion Date: November 2015

Arms and Interventions

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 Name: Zilretta
Placebo Comparator: Placebo; Normal Saline Single 5 mL intra-articular (IA) injection	Drug: Placebo; Single 5 mL IA injection; Other Name: Normal Saline

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Baseline and 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."

Secondary Outcome Measures :

1. Change From Baseline to Week 12 for WOMAC C (Function Subscale) [ Time Frame: Baseline and Week 12 ]
   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.
2. Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC) [ Time Frame: Baseline and Week 12 ]
   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.
3. 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 [ Time Frame: Baseline and Weeks 16, 20 and 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."

Other Outcome Measures:

1. Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria [ Time Frame: Weeks 4, 8 and 12 ]
   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.
2. Change From Baseline to Week 12 for WOMAC C (Function Subscale) [ Time Frame: Baseline and Week 12 ]
   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.
3. Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC) [ Time Frame: Baseline and Week 12 ]
   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.
4. Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores [ Time Frame: Baseline and Up to Week 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 12, 16, 20, and 24 are specified as the primary and secondary endpoints for the 32 mg group and the placebo group
5. Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function [ Time Frame: Baseline and Weeks 4, 8, 16, 20 and 24 (Week 12 data is represented in the secondary outcome measure) ]
   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.
6. Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain [ Time Frame: Baseline and 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.
7. Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC [ Time Frame: Baseline and Weeks 4, 8, 16, 20, and 24 (Week 12 data reported in secondary outcome measure) ]
   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.
8. 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 [ Time Frame: 12 weeks ]
   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."
9. Time to Onset of Pain Relief [ Time Frame: Baseline up to 24 Weeks after administration of study treatment ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Alabama

Anniston, Alabama, United States, 36207

Birmingham, Alabama, United States, 35216

Mobile, Alabama, United States, 36608

United States, Arizona

Phoenix, Arizona, United States, 85023

Tucson, Arizona, United States, 85704

United States, Arkansas

Hot Springs, Arkansas, United States, 71913

United States, 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

United States, Connecticut

Stamford, Connecticut, United States, 06905

United States, 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

United States, Georgia

Marietta, Georgia, United States, 30060

United States, Indiana

Evansville, Indiana, United States, 47713

United States, Kentucky

Paducah, Kentucky, United States, 42003

United States, Maryland

Wheaton, Maryland, United States, 20902

United States, Massachusetts

New Bedford, Massachusetts, United States, 02740

United States, Michigan

Troy, Michigan, United States, 48085

United States, Missouri

Kansas City, Missouri, United States, 64114

United States, Nevada

Las Vegas, Nevada, United States, 89106

United States, New Mexico

Albuquerque, New Mexico, United States, 87102

United States, New York

New York, New York, United States, 10018

Rochester, New York, United States, 14609

United States, North Carolina

Raleigh, North Carolina, United States, 27612

United States, Oklahoma

Oklahoma City, Oklahoma, United States, 73112

United States, Pennsylvania

Altoona, Pennsylvania, United States, 16602

Duncansville, Pennsylvania, United States, 16635

United States, South Carolina

Mount Pleasant, South Carolina, United States, 29464

United States, Texas

Dallas, Texas, United States, 75231

Houston, Texas, United States, 77055

San Antonio, Texas, United States, 78258

Victoria, Texas, United States, 77901

United States, Virginia

Danville, Virginia, United States, 24541

Canada, Ontario

Kitchener, Ontario, Canada

Sarnia, Ontario, Canada

Toronto, Ontario, Canada

Windsor, Ontario, Canada

Canada

Quebec, Canada

Sponsors and Collaborators

Flexion Therapeutics, Inc.

Investigators

• Study Director: Neil Bodick, MD; Flexion Therapeutics

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Flexion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02116972
• Other Study ID Numbers: FX006-2014-006
• First Posted: April 17, 2014
• Results First Posted: March 20, 2018
• Last Update Posted: March 20, 2018
• Last Verified: March 2018

Keywords provided by Flexion Therapeutics, Inc.:

osteoarthritis; knee; pain; corticosteroid; intra-articular; injection

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; FX006; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors