Study to Evaluate the Effect of FX006 on Synovial Inflammation in Patients With OA of the Knee

Study Overview
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Brief Summary
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This is an open-label study assessing the effect of the administration of a single intra-articular (IA) injection of FX006 32 mg on synovial volume in patients with osteoarthritis (OA) of the knee.

Detailed Description
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This is an open-label study assessing the effect of the administration of a single intra-articular (IA) injection of FX006 32 mg on synovial volume in patients with osteoarthritis (OA) of the knee. The study will be conducted in male and female patients who are ≥ 40 years of age. Eligible patients who provide written consent and meet all entry criteria will undergo initial ultrasound examination and MRI with contrast of the index knee, and then receive a single IA injection of FX006 administered to the index knee at Baseline/Day 1. Patients will return to the clinic at Weeks 6 and 24 for an MRI with contrast of the index knee and other assessments. Patients must also have a blood sample drawn for Estimated Glomerular Filtration Rate (eGFR) testing within 30 days prior to the scheduled MRIs. In addition, a patient questionnaire will be administered and adverse events (AEs) and concomitant medication updates will be collected via telephone at Weeks 12 and 18.

Official Title
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An Open-Label Study to Evaluate the Effect of the Administration of FX006 on Synovial Inflammation in Patients With Osteoarthritis of the Knee

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: FX006 32 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 ≥ 40 years of age Body mass index (BMI) ≤ 40 kg/m^2 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 Symptoms associated with OA of the index knee for ≥ 6 months prior to Screening (patient self-report is acceptable) 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 based on X-ray performed during Screening (centrally read) Exclusion Criteria: Any inflammatory arthritis including reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, gout or secondary OA from gout History of infection or crystal disease in the index knee joint Unstable index knee joint (such as a torn anterior cruciate ligament) within 12 months of Screening Surgery or arthroscopy of the index knee within 12 months of Screening IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening IA treatment of the index knee with hyaluronic acid (investigational or marketed) within 6 months of Screening IV or IM corticosteroids (investigational or marketed) within 3 months of Screening Oral corticosteroids (investigational or marketed) within 1 month of Screening Any other IA drug/biologic in the index knee within 6 months of Screening or 5 half-lives (whichever is longer) (e.g., platelet rich plasma (PRP) injection, stem cells, prolotherapy and amniotic fluid injection) Prior administration of FX006 eGFR results <40 mL/minute Any contraindication to MRI Scanning (e.g., presence of certain ferromagnetic foreign bodies or electronic devices including most cardiac pacemakers, claustrophobia) Known hypersensitivity to any form of radiographic contrast 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FX006 32 mg<br>Single intra-articular (IA) injection of FX006 32 mg | Drug: FX006 32 mg<br>* Extended-release 32 mg FX006 IA injection<br>* Other names: Zilretta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Standardized Change in Synovial Volume (SV) at 6 Weeks | Synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. Standardization was performed by dividing the model-derived least squares means and corresponding confidence intervals by the adjusted standard deviation (SD). Therefore, the mean standardized change represents the change in synovial volume expressed in standard deviation units. | Baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Absolute Change in Synovial Volume at 6 Weeks | Mean absolute change from baseline at 6 weeks in synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. The least squares mean changes are estimated using a mixed effects model for repeated measures with fixed effects for study time point, study site, baseline score and baseline femur bone volume (mm^3) and a random effect for patient. | Baseline to Week 6 | 
| Mean Standardized Change in Synovial Volume (SV) at 24 Weeks | Synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. Standardization was performed by dividing the model-derived least squares means and corresponding confidence intervals by the adjusted standard deviation (SD). Therefore, the mean standardized change represents the change in synovial volume expressed in standard deviation units. | Baseline to Week 24 | 
| Mean Absolute Change in Synovial Volume at 24 Weeks | Mean absolute change (mm^3) from baseline at 24 weeks in synovial volume (mm^3) as measured by MRI and read by a central imaging vendor. The least squares mean changes are estimated using a mixed effects model for repeated measures with fixed effects for study time point, study site, baseline score and baseline femur bone volume (mm^3) and a random effect for patient. | Baseline to Week 24 | 

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