Proof of Concept Study Comparing FX006 to Kenalog®-40 in Patients With Post-Traumatic Osteoarthritis of the Knee

A Double-Blind, Randomized, Parallel Group, Proof of Concept Study Comparing FX006 to Kenalog®-40 in Patients With Post-Traumatic Osteoarthritis of the Knee

This study was a double-blind, randomized, parallel group, proof of concept study comparing FX006 to Kenalog®-40 (triamcinolone acetonide injectable suspension, USP) in patients with post-traumatic osteoarthritis of the knee.

Study Overview

• Status: Terminated
• Conditions: Post-traumatic Osteoarthritis of the Knee
• Intervention / Treatment: Drug: FX006 32 mg; Drug: TCA IR 40 mg

Detailed Description

This study was a double-blind, randomized, parallel group, proof of concept study patients with post-traumatic osteoarthritis (PTOA) of the knee. Approximately 124 eligible patients were intended to be randomized to one of the two treatment groups (1:1) and treated with a single intra-articular (IA) injection of:

• 32 mg of FX006
• 40 mg of Kenalog®-40 (triamcinolone acetonide injectable suspension, USP)

Each prospective patient underwent a screening evaluation to confirm a diagnosis of PTOA of the knee and concurrence with all other eligibility criteria. Patients were be treated on Day 1 (Baseline) and returned to the clinic at Weeks 4, 8 and 12 for evaluation of safety and efficacy.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78234
      • San Antonio Military Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (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 ≥20 and ≤50 years of age
• Diagnosis of post-traumatic OA of the knee
• Kellgren-Lawrence (K-L) Grade 2 or 3 in the index knee within 6 months prior to or at Screening
• 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 and therapies during the study

Exclusion Criteria:

• Prior osteotomy of the index knee
• Any condition that could possibly confound the patient's assessment of index knee pain in the judgement of the Investigator (i.e., ipsilateral hip OA, gout, radicular low back pain and hip pain that is referred to the knee that could cause misclassifcation, pain in any other area of the lower extremeties or back that is equal to 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, or clinical signs and symptoms of active infection of the index knee
• Crystal disease of the index knee within one month of Screening
• Disease secondary to surgical treatment of Shatzker grade IV, V, or VI tibial plateau fractures (OTA classification C2 or C3); surgical treatment of OTA calssifcation C2 or C3 distal femur fractures; or >2mm of articular incongruity after surgery
• 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
• Prior arthroplasty of any type of the index knee or planned/anticipated surgery of the index knee during the study period
• Type 1 or Type 2 diabetes requiring insulin
• 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FX006 32mg; Single 5 mL intra-articular (IA) injection Extended-release formulation	Drug: FX006 32 mg; Experimental; Other Names: Zilretta
Active Comparator: TCA IR 40 mg; Single 1 mL intra-articular (IA) injection Immediate-release formulation	Drug: TCA IR 40 mg; Comparator; Other Names: Kenalog®-40; Triamcinolone Acetonide Crystalline Suspension (TAcs)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Change From Baseline in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores Over Weeks 5 to 10	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."	5-10 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores, Change From Baseline to Each Week and Average Change From Baseline Over Weeks 1 to 12 and Weeks 4 to 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."	12 Weeks
Proportion of Patients Experiencing a >20% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Each Week		12 Weeks
Proportion of Patients Experiencing a >50% or >30% Decrease in Pain From Baseline in Weekly Mean of Average Daily 24-hr Pain Intensity Scores at Each Week		12 Weeks
Proportion of Patients Experiencing Each of >50% or >30% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Each Week		12 Weeks
WOMAC A (Pain Subscale)	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12	12 weeks
WOMAC A1 (Pain on Walking Question)	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12	12 weeks
WOMAC B (Stiffness)	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12	12 weeks
WOMAC C (Function)	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12	12 weeks
WOMAC (Total):	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12	12 weeks
Knee Injury and Osteoarthritis Score (KOOS)	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12	12 weeks
Patient Global Impression of Change (PGIC) at Weeks 4, 8 and 12		12 weeks
Clinical Global Impression of Change (CGIC) at Weeks 4, 8 and 12		12 weeks
Percent of Responders (Defined as Patients With High Improvement in Pain or Function) According to OMERACT-OARSI Criteria at Weeks 4, 8 and 12		12 weeks
Time to Onset of Pain Relief	Time to onset of pain relief in days is defined as the time from first dose to the first daily pain assessment showing >30% improvement from the weekly mean of the average daily (24-hr) pain intensity scores at Baseline	Baseline to >30% improvement
Average Weekly and Total Consumption of Rescue Medication		12 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: May 27, 2015
• First Submitted That Met QC Criteria: June 8, 2015
• First Posted (Estimated): June 11, 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; Intra-articular; Injection; Post-traumatic
• 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: FX006-2014-007