Study of FX006 in Patients With Osteoarthritis of the Knee

• Change from Baseline to each of Weeks 8, 10 and 12 in weekly mean of the average daily (24-hour) pain intensity score. [ Time Frame: at 8, 10 and 12 weeks ] [ Designated as safety issue: No ]
• Incidence of treatment emergent adverse events [ Time Frame: through 12 weeks ] [ Designated as safety issue: Yes ]

• Change from Baseline to Week 8 in weekly average 24-hour average pain intensity [ Time Frame: at 8 weeks ] [ Designated as safety issue: No ]
• Incidence of treatment emergent adverse events [ Time Frame: through 12 weeks ] [ Designated as safety issue: Yes ]

• Change from Baseline to each of Weeks 1, 2, 3, 4, 5, 6, 7, 9 and 11 in weekly mean of the average (24-hour) pain intensity score. [ Time Frame: weekly through 12 weeks ] [ Designated as safety issue: No ]
• Time of onset of pain relief [ Time Frame: weekly through 12 weeks ] [ Designated as safety issue: No ]
• Continuous responder at each study week [ Time Frame: weekly through 12 weeks ] [ Designated as safety issue: No ]
• WOMAC A (pain subscale) change from Baseline [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• WOMAC B (stiffness subscale) change from Baseline [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• WOMAC C (function subscale) change from Baseline [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• WOMAC (total) change from Baseline [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• Percent of responders (defined as patients with high improvement in pain or function) according to OMERACT-OARSI criteria [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• Change in patient's and clinical observer's global impression of change scores [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• Average weekly and total consumption of rescue medications [ Time Frame: weekly through 12 weeks ] [ Designated as safety issue: No ]
• Pharmacokinetic profile [ Time Frame: through 12 weeks ] [ Designated as safety issue: No ]
• WOMAC A1 (pain on walking question) change from Baseline [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]

• Change from Baseline to Weeks 1, 2, 3, 4, 5, 6, 7, 9, 10, 11 and 12 in weekly average 24-hour average pain intensity. [ Time Frame: weekly through 12 weeks ] [ Designated as safety issue: No ]
• Time of onset of pain relief [ Time Frame: weekly through 12 weeks ] [ Designated as safety issue: No ]
• Continuous responder at each study week [ Time Frame: weekly through 12 weeks ] [ Designated as safety issue: No ]
• WOMAC A (pain subscale) change from Baseline [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• WOMAC B (stiffness subscale) change from Baseline [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• WOMAC C (function subscale) change from Baseline [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• WOMAC (total) change from Baseline [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• Percent of responders (defined as patients with high improvement in pain or function) according to OMERACT-OARSI criteria [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• Change in patient's and clinical observer's global assessment scores [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]
• Average weekly consumption of analgesic medications [ Time Frame: weekly through 12 weeks ] [ Designated as safety issue: No ]
• Pharmacokinetic profile [ Time Frame: through 12 weeks ] [ Designated as safety issue: No ]
• WOMAC A1 (pain on walking question) change from Baseline [ Time Frame: at 1, 2, 4, 8 and 12 weeks ] [ Designated as safety issue: No ]

The purpose of the study is to evaluate the safety, efficacy and pharmacokinetics of FX006 in patients with osteoarthritis of the knee.

This study will be a multi-center, randomized, double-blind, active comparator, parallel-group, single dose design.

Up to 224 patients with knee OA will be randomized to be treated with a single IA injection of either 10, 40, or 60 mg of FX006 or 40 mg of Kenalog-40.

Each patient will be evaluated for a total of 12 weeks following a single IA injection. Following screening, safety and efficacy and PK will be evaluated at 7 out-patient visits (Days 1 [Baseline], 2, 8, 15, 29, 57 and 85).

Analgesic effect will be assessed using weekly average of daily (24 hour) pain intensity score, Western Ontario & McMaster University Osteoarthritis Index (WOMAC) and patient and clinical global impression of change.

• Drug: FX006
  Single intra-articular injection
• Drug: Commercially available triamcinolone acetonide
  Single intra-articular injection

• Experimental: FX006 10 mg
  Intervention: Drug: FX006
• Experimental: FX006 40 mg
  Intervention: Drug: FX006
• Experimental: FX006 60 mg
  Intervention: Drug: FX006
• Active Comparator: commercially available triamcinolone acetonide (40 mg)
  Intervention: Drug: Commercially available triamcinolone acetonide

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