Study of FX006 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 evaluate the safety, efficacy and pharmacokinetics of FX006 in patients with osteoarthritis of the knee.

Detailed Description
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Study FX006-2011-001 was a multi-center, randomized, double-blind, active comparator, parallel-group, single-dose study designed to assess the magnitude and duration of pain relief of three doses (10, 40, and 60 mg) of FX006, an extended-release formulation of TCA, relative to commercially-available TCA IR. The general tolerability of a single injection of FX006 also was assessed. Secondary objectives included exploration of the effect of FX006 on functional improvement, responder status, time to onset of pain relief, global impressions of change, and consumption of analgesic medications and evaluation of the PK profile of single injection of the three dose levels of FX006. The study was planned to be conducted in up to 224 male and female patients ≥40 years of age with OA of the knee enrolled at 22 study centers in the US, Australia, and Canada.

Official Title
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A Double-Blind, Randomized, Parallel Group, Dose-Ranging Study Comparing FX006 to Commercially Available Triamcinolone Acetonide Injectable Suspension 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: TCA IR


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 Diagnosis of unilateral or bilateral OA of the knee for at least 6 months prior to Screening with confirmation of OA according to American College of Rheumatology Criteria for Classification of Idiopathic OA of the Knee (clinical and radiological) based on an X-ray performed within 6 months prior to Screening or during the Screening period 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 of infection in the index joint Clinical signs and symptoms of active knee infection or crystal disease of the index knee Presence of surgical hardware or other foreign body in the index knee Unstable joint (such as a torn anterior cruciate ligament) 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 Oral, inhaled and intranasal corticosteroids (investigational or marketed) within 1 month of Screening Prior arthroscopic or open surgery of the index knee within 12 months of Screening Planned/anticipated surgery of the index knee during the study period Active or history of malignancy within the last 5 years, with the exception of resected basal cell carcinoma, squamous cell carcinoma of the skin, or resected cervical atypia or carcinoma in situ Insulin-dependent diabetes Active psychiatric disorder including psychosis and major depressive disorder History of or active Cushing's syndrome Any other clinically significant acute or chronic medical conditions (e.g., uncontrolled diabetes) Skin breakdown at the knee where the injection would take place 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 10 mg<br>Single 3 mL intra-articular (IA) injection Extended-Release Formulation | Drug: FX006<br>* Single 3 mL intra-articular injection<br>|
| Experimental: FX006 40 mg<br>Single 3 mL intra-articular (IA) injection Extended-Release Formulation | Drug: FX006<br>* Single 3 mL intra-articular injection<br>|
| Experimental: FX006 60 mg<br>Single 3mL intra-articular (IA) injection Extended-Release Formulation | Drug: FX006<br>* Single 3 mL intra-articular injection<br>|
| Active Comparator: TCA IR 40 mg<br>Single 1 mL intra-articular (IA) injection Immediate-Release Triamcinolone Acetonide | Drug: TCA IR<br>* Single 1 mL intra-articular 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 8 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | 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. | 8 weeks | 
| Change From Baseline to Week 10 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | 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. | 10 weeks | 
| Change From Baseline to Week 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | 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. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg | 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. | Weeks 8, 10 and 12 | 
| Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | 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. | Weeks 1-7 and Week 9 and 11 | 
| WOMAC A (Pain Subscale) Change From Baseline at Week 8 | 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. | 8 weeks | 
| WOMAC A1 (Pain on Walking Question) Change From Baseline at Week 8 | 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. | 8 weeks | 
| WOMAC B (Stiffness Subscale) Change From Baseline at Week 8 | 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. | 8 weeks | 
| WOMAC C (Function Subscale) Change From Baseline at Week 8 | 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. | 8 weeks | 
| Percent of Responders According to OMERACT-OARSI Criteria at Week 8 | Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International. Responders are defined as participants with high improvement in pain or function. | 8 weeks | 
| Responder Status as Defined by the Proportion of Patients Achieving >50% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 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. | 8 weeks | 
| Responder Status as Defined by the Proportion of Patients Achieving >30% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 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. | 8 weeks | 
| Responder Status as Defined by the Proportion of Patients Achieving >20% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 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. | 8 weeks | 
| Patient Global Impression of Change Scores at Week 8 | 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. | Week 8 | 
| Clinical Global Impression of Change Scores at Week 8 | The Clinical Global Impression of Change is a scale that the clinician uses to assess the participants' global function and determine if there has been an improvement or not. The clinician selects one response from the response options that gives the most accurate description of the participant's 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. | 8 weeks | 
| Average Weekly and Total Consumption of Rescue Medications Over 8 Weeks. |  | 8 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