Clinical trial NCT02116972: Study of FX006 vs Normal Saline in Patients With Osteoarthritis of the Knee
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis of the Knee
Keywords: osteoarthritis
knee
pain
corticosteroid
intra-articular
injection
Lead sponsor: Pacira Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2014-04-17
Enrollment: 310
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline to Week 12 for WOMAC C (Function Subscale)
timeFrame: Baseline and Week 12
measure: Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC)
timeFrame: Baseline and Week 12
measure: 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
timeFrame: Baseline and Weeks 16, 20 and 24
Other outcomes:
measure: Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria
timeFrame: Weeks 4, 8 and 12
measure: Change From Baseline to Week 12 for WOMAC C (Function Subscale)
timeFrame: Baseline and Week 12
measure: Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC)
timeFrame: Baseline and Week 12
measure: Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores
timeFrame: Baseline and Up to Week 24
measure: Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function
timeFrame: Baseline and Weeks 4, 8, 16, 20 and 24 (Week 12 data is represented in the secondary outcome measure)
measure: Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain
timeFrame: Baseline and Weeks 4, 8, 12, 16, 20 and 24
measure: Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC
timeFrame: Baseline and Weeks 4, 8, 16, 20, and 24 (Week 12 data reported in secondary outcome measure)
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
timeFrame: 12 weeks
measure: Time to Onset of Pain Relief
timeFrame: Baseline up to 24 Weeks after administration of study treatment
Locations:
city: Anniston
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Hot Springs
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: Canoga Park
country: United States
state: California
city: El Cajon
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: North Hollywood
country: United States
state: California
city: San Diego
country: United States
state: California
city: Stamford
country: United States
state: Connecticut
city: DeLand
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Pinellas Park
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Marietta
country: United States
state: Georgia
city: Evansville
country: United States
state: Indiana
city: Paducah
country: United States
state: Kentucky
city: Wheaton
country: United States
state: Maryland
city: New Bedford
country: United States
state: Massachusetts
city: Troy
country: United States
state: Michigan
city: Kansas City
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Albuquerque
country: United States
state: New Mexico
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Raleigh
country: United States
state: North Carolina
city: Oklahoma City
country: United States
state: Oklahoma
city: Altoona
country: United States
state: Pennsylvania
city: Duncansville
country: United States
state: Pennsylvania
city: Mount Pleasant
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Victoria
country: United States
state: Texas
city: Danville
country: United States
state: Virginia
city: Kitchener
country: Canada
state: Ontario
city: Sarnia
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Windsor
country: Canada
state: Ontario
city: Quebec
country: Canada
Study officials:
affiliation: Flexion Therapeutics
name: Neil Bodick, MD
role: STUDY_DIRECTOR
References:
citation: 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.