Study of FX006 vs Normal Saline in Patients With Osteoarthritis of the Knee

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

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).

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.

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