Euflexxa for the Treatment of Osteoarthritis

The FLEXX trial was the first well-controlled, randomized, double-blind, multicenter study
evaluating the efficacy of Euflexxa (1% sodium hyaluronate) therapy for knee osteoarthritis.
Five-hundred-and-eighty patients were randomized to receive either Euflexxa or normal saline.
There were significant improvements in the Visual analogue scale score Osteoarthritis
Research Society International responder index, HRQoL, and function at 26-week follow-up.1
However, the FLEXX trial did not evaluate changes in synovial fluid bio-marker levels. The
present study will be a prospective pilot study of 25 subjects who will receive
intra-articular Euflexxa. The primary objective of this study is to prospectively determine,
at 6-weeks, and 6-months post treatment, the changes in levels of synovial fluid biomarkers
from pre- to post-injection in patients who receive Euflexxa. In addition, we will assess
patient reported pain and patient reported outcomes up to 2 years from initiation of study.

Inclusion criteria:

1. OA of the knee by American College of Rheumatology criteria

2. Those who failed non-pharmacological measures or simple analgesics

3. moderate to severe pain score of 41 to 90 mm recorded on 100-mm visual analog scale
(VAS) immediately following a 50-foot walk

4. bilateral standing anterior-posterior radiograph demonstrating Kellgren and Lawrence
grade 2 or 3 OA of the target knee

5. ability and willingness to use only acetaminophen as the analgesic (rescue) study
medication

6. unassisted walking 50 feet on a flat surface and going up and down stairs

7. willingness and ability to complete efficacy and safety questionnaires

Exclusion criteria:

1. Age less than 18 years

2. any major injury to the target knee within the prior 12 months

3. any surgery to the target knee within the prior 12 months

4. surgery to the contralateral knee or other weight-bearing

5. inflammatory arthropathies

6. gout or pseudogout within the previous 6 months

7. radiographic acute fracture, severe loss of bone density, avascular necrosis, and/or
severe bone or joint deformity in the target knee

8. osteonecrosis of either knee

9. fibromyalgia, pes anserine bursitis, lumbar radiculopathy, and/or neurogenic or
vascular claudication

10. target knee joint infection or skin disorder/ infection within the previous 6 months

11. symptomatic OA of the hips, spine, or ankle; known hypersensitivity to acetaminophen,
IA-BioHA, or phosphate-buffered saline solution

12. Women of childbearing potential who are pregnant, nursing, or planning to become
pregnant, and those who do not agree to remain on an acceptable method of birth
control throughout the study

13. history of immune disorders; vascular insufficiency of lower limbs or peripheral
neuropathy

14. current treatment or treatment of cancer within the previous 2 years (excluding basal
cell or squamous cell carcinoma of the skin)

15. active liver or renal disease

16. any clinically significant abnormal laboratory value [to be defined in detail at a
later point]

17. any intercurrent chronic disease or condition that might interfere with the completion
of the study

18. participation in any experimental device study within the prior 6 months or any
experimental drug study within the prior month