Clinical trial NCT02357459: Study of FX006 for the Treatment of Pain in Patients With Osteoarthritis of the Knee
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthritis of the Knee
Keywords: osteoarthritis
knee
pain
corticosteroid
intra-articular
injection
Lead sponsor: Pacira Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2015-02-06
Enrollment: 486
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 safety and efficacy of FX006 for the treatment of pain in patients with osteoarthritis of the knee.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline and 12 Weeks
Secondary outcomes:
measure: 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
timeFrame: Baseline to 12 Weeks
measure: AUE of Change From Baseline in Weekly Mean of the ADP Scores From Baseline to Week 12 for FX006 Relative to TCA IR
timeFrame: Baseline to 12 Weeks
measure: 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
timeFrame: Baseline through 12 Weeks
measure: AUE of Change From Baseline in Weekly Mean of the ADP Scores From Baseline to Week 24 for FX006 Relative to Placebo
timeFrame: Baseline to 24 Weeks
Other outcomes:
measure: Change From Baseline to Each Week in Weekly Mean of the ADP Scores
timeFrame: Weeks 1-11 & Weeks 13-24
measure: Change From Baseline Over Time for WOMAC A (Pain Subscale) at Weeks 4, 8, 12, 16, 20 and 24.
timeFrame: Weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline Over Time for WOMAC B (Stiffness Subscale) at Weeks 4, 8, 12, 16, 20 and 24
timeFrame: Weeks 4, 8, 12, 16, 20 and 24
measure: Change From Baseline Over Time for WOMAC C (Function Subscale) at Weeks 4, 8, 12, 16, 20 and 24
timeFrame: Weeks 4, 8, 12, 16, 20 and 24
measure: 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
timeFrame: Weeks 4, 8, 12, and 24
measure: 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)
timeFrame: Weeks 1-24
measure: 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)
timeFrame: Weeks 1-24
measure: Time to Onset of Pain Relief
timeFrame: Baseline to >30% improvement (measured up to 30 days)
measure: Average Weekly and Total Consumption of Rescue Medications at Each Week (Weeks 1-24)
timeFrame: Weeks 1-24
Locations:
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Anaheim
country: United States
state: California
city: Canoga Park
country: United States
state: California
city: North Hollywood
country: United States
state: California
city: San Diego
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Atlantis
country: United States
state: Florida
city: DeLand
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Prairie Village
country: United States
state: Kansas
city: Albuquerque
country: United States
state: New Mexico
city: Cary
country: United States
state: North Carolina
city: Cary
country: United States
facility: PMG Research of Cary
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Duncansville
country: United States
state: Pennsylvania
city: Knoxville
country: United States
facility: PMG Research of Knoxville
state: Tennessee
city: Knoxville
country: United States
facility: PMG Research of Knoxville
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Newport News
country: United States
state: Virginia
city: Broadmeadow
country: Australia
state: New South Wales
city: Geelong
country: Australia
state: New South Wales
city: Merewether
country: Australia
state: New South Wales
city: St. Leonards
country: Australia
state: New South Wales
city: Sherwood
country: Australia
state: Queensland
city: Malvern
country: Australia
state: Victoria
city: Quebec
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Windsor
country: Canada
state: Ontario
city: Aalborg
country: Denmark
city: Ballerup
country: Denmark
city: Vejle
country: Denmark
city: Tallinn
country: Estonia
city: Hong Kong
country: Hong Kong
city: Vilnius
country: Lithuania
city: Bucharest
country: Romania
Study officials:
affiliation: Flexion Therapeutics
name: Neil Bodick, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.