Study of FX006 vs Normal Saline 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 magnitude and duration of pain relief of a single IA injection of 2 doses (16 and 32 mg) of FX006, an extended-release formulation of TCA, relative to normal saline (placebo control).

Detailed Description
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This was a double-blind, randomized, parallel group, dose-ranging, single-dose study. The study was conducted in male and female patients ≥40 years of age with OA of the knee. Approximately 300 patients with OA of the knee were randomized, using a centralized randomization procedure, to 1 of 3 treatment groups (1:1:1) and treated with a single IA injection of: 16 mg FX006, 32 mg FX006, or normal saline (placebo). 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 over approximately 6 to 7 months.

Official Title
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A Double-Blind, Randomized, Parallel Group, Dose-Ranging 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 32 mg
* Drug: Placebo
* Drug: FX006 16 mg


Participation Criteria
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Eligibility Criteria
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Main 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 documented diagnosis of OA of the index knee made 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 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 Main Exclusion Criteria: Ipsilateral hip OA Fibromyalgia, chronic pain syndrome or other concurrent medical or arthritic conditions which could interfere with the evaluation of the index knee History of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis or amyloidosis History of arthritides due to crystals (e.g., gout, pseudogout) History or clinical signs and symptoms of infection in the index joint Knee pain that is not clinically attributable to OA of the knee (e.g., 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 to or greater than the index knee pain 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) corticosteroids (investigational or marketed) within 3 months of Screening Oral corticosteroids (investigational or marketed) within 1 month of Screening Inhaled, intranasal and topical corticosteroids (investigational or marketed) within 2 weeks 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 16 mg<br>Single 5 mL intra-articular (IA) injection Extended-release formulation | Drug: FX006 16 mg<br>* Single 5 mL IA injection<br>|
| 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;|
| Placebo Comparator: Placebo<br>Normal Saline Single 5 mL intra-articular (IA) injection | Drug: Placebo<br>* Single 5 mL IA injection<br>* Other names: Normal Saline;|

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 Intensity Scores for 32 mg FX006 Versus Placebo | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no painand 10 indicates pain as bad as you can imagine. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 for WOMAC C (Function Subscale) | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. | Baseline and Week 12 | 
| Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC) | The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. | Baseline and Week 12 | 
| Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores | 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. | Baseline and Weeks 16, 20 and 24 | 

 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