Study to Compare Exposure of TA Following Administration of Either FX006 or TAcs in Patients With Bilateral Knee OA

Study Overview
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Brief Summary
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This is a randomized, open-label, parallel group study to compare systemic exposure of triamcinolone acetonide following administration into both knees of either FX006 or TAcs.

Detailed Description
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This is a randomized, open label, parallel group study that will be conducted in male and female patients ≥ 40 years of age with bilateral knee OA. Approximately 24 patients will be randomized to one of two treatment groups (1:1) and treated with IA injections to both knees of either: extended-release FX006 64 mg total dose (approximately 12 patients) or immediate-release TAcs 80 mg total dose (approximately 12 patients) Each patient will be screened to confirm the diagnosis of OA and eligibility based on the inclusion/exclusion requirements and will be randomized to treatment on Day 1. Following screening, pharmacokinetics (PK) and safety will be evaluated at 6 out-patient visits scheduled on Study Days 1 [calendar day of injection], 2, 8, 15, 29, and 43.

Official Title
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A Randomized, Open-label, Parallel Group Study in Patients With Bilateral Knee Osteoarthritis Comparing the Systemic Exposure of Triamcinolone Acetonide Following Administration Into Both Knees of Either Extended-release FX006 or Immediate-release TAcs (Triamcinolone Acetonide Suspension)

Conditions
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Bilateral Knee Osteoarthritis

Intervention / Treatment
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* Drug: FX006 32 mg
* Drug: TAcs 40 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written consent to participate in the study Male or female greater than or equal to 40 years of age Symptoms consistent with OA in both knees for greater than or equal to 6 months prior to Screening (patient reported is acceptable) Currently meets ACR Criteria (clinical and radiological) for OA in both knees Knee pain in both knees for greater than 15 days over the last month (as reported by the patient) Body mass index (BMI) less than or equal to 40 kg/m2 Morning serum cortisol result within normal range at Screening (5-23 mcg/dL or 138-635 nmol/dL) Ambulatory and in good general health Willing and able to comply with the study procedures and visit schedules and able to follow verbal and written instructions. Willing to abstain from use of protocol-restricted medications during the study Exclusion Criteria: Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease History of infection in either knee joint Clinical signs and symptoms of active knee infection or crystal disease in either knee within 1 month of Screening Unstable joint (such as a torn anterior cruciate ligament) in either knee within 12 months of Screening Presence of surgical hardware or other foreign body in either knee Surgery or arthroscopy of either knee within 12 months of Screening IA treatment of any joint with any of the following agents within six (6) months of Screening: any corticosteroid preparation (investigational or marketed, including FX006), any biologic agent (e.g., platelet rich plasma (PRP) injection, stem cells, prolotherapy, amniotic fluid injection; investigational or marketed). IA treatment in either knee with hyaluronic acid (investigational or marketed) within 6 months of Screening Parenteral or oral corticosteroids (investigational or marketed) within 3 months of Screening Inhaled, intranasal or topical corticosteroids (investigational or marketed) within 2 weeks of Screening Females who are pregnant or nursing or plan to become pregnant during the study; men who plan to conceive during the study

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FX006 32 mg<br>Two intra-articular (IA) injections of FX006 32 mg (total dose of 64 mg) | Drug: FX006 32 mg<br>* Drug: Extended-release 32 mg FX006 IA injection into each knee (total 64 mg dose)<br>* Other names: Zilretta;|
| Active Comparator: TAcs 40 mg<br>Two intra-articular (IA) injections of TAcs 40 mg (total dose of 80 mg) | Drug: TAcs 40 mg<br>* Drug: Immediate-release 40mg TAcs IA injection into each knee (total 80 mg dose)<br>* Other names: TCA-IR 40;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Plasma drug concentrations (pg/mL) by Time Point across FX006 and TAcs treatment arms in plasma. For the PK analysis and individual concentration vs. time plots, a concentration that is BLOQ is assigned a value of zero if it occurs in a profile before the first measurable concentration. If a BLOQ value occurs after a measurable concentration in a profile and is followed by a value above the lower limit of quantification, then the BLOQ is treated as missing data. If a BLOQ value occurs at the end of the collection interval (after the last quantifiable concentration) it is set to zero. If two BLOQ values occur in succession after Cmax, the profile is deemed to have terminated at the first BLOQ value and any subsequent concentrations are set to zero for PK calculations | 43 days | 
| Incidence of Treatment Emergent Adverse Events | Safety analyses were conducted using the safety population. Analyses of adverse events will be performed for those events that are considered treatment emergent, where treatment emergent is defined as any adverse event with onset after the administration of study medication in the first knee through the end of the study or any event that was present at baseline but worsened in intensity through the end of the study. Severity of Adverse events were graded by the Principal Investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The grading went from Grade 1 (Mild) to Grade 5 (Death related to AE). | 43 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Knee, Corticosteroid, Bilateral, Pain, Intra-articular, Injection