Study of FX006 for the Treatment of Pain in Patients With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Osteoarthritis of the Knee

Intervention / Treatment
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* Drug: FX006
* Drug: Placebo
* Drug: TCA IR 40


Participation Criteria
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Eligibility Criteria
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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

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FX006 32mg<br>Single 5 mL intra-articular (IA) injection Extended-release Formulation | Drug: FX006<br>* Single 5 mL IA injection<br>* Other names: Zilretta;|
| Placebo Comparator: Normal Saline<br>Single 5 mL intra-articular (IA) injection | Drug: Placebo<br>* Single 5 mL IA injection<br>* Other names: Normal Saline;|
| Active Comparator: TCA IR 40 mg<br>Single 1 mL intra-articular (IA) injection TCA IR 40 mg: 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 |
| --- | --- | --- |
| 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 | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where ) indicates no pain and 10 indicates pain as bad as you can imagine. | Baseline and 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where ) indicates no pain and 10 indicates pain as bad as you can imagine. | Baseline to 12 Weeks | 
| AUE of Change From Baseline in Weekly Mean of the ADP Scores From Baseline to Week 12 for FX006 Relative to TCA IR | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where ) indicates no pain and 10 indicates pain as bad as you can imagine. | Baseline to 12 Weeks | 
| 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 | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where ) indicates no pain and 10 indicates pain as bad as you can imagine. | Baseline through 12 Weeks | 
| AUE of Change From Baseline in Weekly Mean of the ADP Scores From Baseline to Week 24 for FX006 Relative to Placebo | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where ) indicates no pain and 10 indicates pain as bad as you can imagine. | Baseline to 24 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