Study to Characterize the PK and Local Extent and Duration of Exposure From FX006 in Patients With OA of the Knee

Study Overview
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Brief Summary
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The objectives of this study were to characterize the local extent and duration of exposure of TA from FX006 and TCA IR, characterize the systemic PK of FX006 and TCA IR, and assess the safety and general tolerability of a single 5 mL IA injection of 32 mg FX006 relative to 40 mg of TCA IR in patients with OA of the knee.

Detailed Description
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This study employed an open-label, single administration design and was conducted in male and female patients ≥40 years of age with OA of the knee. Patients were enrolled sequentially with at least 10 patients per cohort as follows: Cohort A: FX006 32 mg, Final Visit at Week 20 Cohort B: FX006 32 mg, Final Visit at Week 16 Cohort C: FX006 32 mg, Final Visit at Week 12 Cohort D: FX006 32 mg, Final Visit at Week 6 Cohort E: FX006 32 mg, Final Visit at Week 1 Cohort F: TCA IR 40 mg, Final Visit Week 6 Each patient was screened to confirm eligibility and assigned to a cohort on Day 1/baseline. Each patient was evaluated for safety during his/her participation in the study at 6, 12, 16, or 20 weeks following a single IA injection depending on the assigned Cohort, and plasma and synovial fluid was collected for drug concentration measurements. Safety and tolerability was assessed by physical examinations, index knee examinations, vital signs, clinical laboratory evaluations, and adverse events (AEs). No efficacy assessments were employed in this study.

Official Title
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An Open-label, Single Administration Study to Characterize the Systemic Pharmacokinetics and Local Extent and Duration of Exposure of Triamcinolone Acetonide From FX006 in Patients With Osteoarthritis of the Knee

Conditions
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Osteoarthritis of the Knee

Intervention / Treatment
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* Drug: FX006 32 mg
* Drug: TCA IR 40


Participation Criteria
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Eligibility Criteria
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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 Symptoms associated with OA of the knee for ≥ 6 months prior to Screening (patient reported is acceptable) Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA 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 Exclusion Criteria: Fibromyalgia, Reiter's syndrome, 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 joint within 12 months of Screening IA corticosteroid (investigational or marketed) in any joint within 6 months of Screening IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening Intravenous or Intramuscular corticosteroids (investigational or marketed) within 3 months of Screening Oral corticosteroids (investigational or marketed) within 1 month of Screening Inhaled, intranasal or topical corticosteroids (investigational or marketed) within 2 weeks of Screening Any other IA investigational drug/biologic use within 6 months of Screening or 5 half-lives (whichever is longer) Prior use of FX006 Women of child-bearing potential not using effective contraception or who are pregnant or nursing

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FX006 32 mg<br>Single 5 mL intra-articular (IA) injection Extended-release formulation | Drug: FX006 32 mg<br>* Single 5 mL IA injection<br>* Other names: Zilretta;|
| Active Comparator: TCA IR 40 mg<br>Commercially available triamcinolone acetonide, single 1 mL intra-articular (IA) injection Immediate-release formulation | Drug: TCA IR 40<br>* Single 1 mL IA injection<br>* Other names: Triamcinolone Acetonide Crystalline Suspension (TAcs);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid | All baseline (pre-treatment) values and all post-baseline values recorded as below LLOQ (<50 pg/mL) were set to zero. Geometric mean summary statistics were computed on adjusted concentration values. One (1) was added to each concentration value observed. BLQ values for the computation of geometric mean are included in the summary with a value of 1 (0+1). | Up to 20 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | All baseline (pre-treatment) values and all post-baseline values that are recorded as below LLOQ were set to zero for analysis and were included in the descriptive mean calculations. Values below LLOQ were not included in geometric mean calculations. | Up to 20 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, knee, pain, corticosteroid, intra-articular, injection