Effectiveness Trial for Evaluating IAHA for PFPS

Objective: To determine the safety and effectiveness of intra-articular hyaluronan (IAHA)
injections for the treatment of symptomatic patellofemoral pain syndrome (PFPS) and determine
if this treatment can provide incremental clinical benefits over standard care for patients
with this diagnosis.

Study Design: Two-arm, single-center, parallel, pragmatic, randomized, non-blinded,
effectiveness trial

Indication for Use: For treatment of adult patients with Patellofemoral Pain Syndrome (PFPS)
who have failed to respond to conservative treatment and simple analgesics (e.g.
acetaminophen).

Setting: University Teaching Hospital, Faculty Practice

Subjects: Male and female patients aged 18-40 diagnosed with symptomatic patellofemoral pain
syndrome (PFPS) that meet all inclusion and exclusion criteria. Approximately 68 subjects
will be enrolled based on a power analysis of sample size estimation.

Methods: Patients signing informed consent will be randomized to one of two groups: (1)
Standard Care, (2) Standard Care plus Intra-articular hyaluronan (IAHA) administered as a
course of 3 consecutive weekly intra-articular injections.

Standard Care is defined as consisting of physical therapy, activity modification (relative
rest), and/or oral analgesic therapy. Upon entering the trial, a specific physical therapy
(PT) protocol will be implemented.

Data will be captured on the study knee history and symptoms. Radiographic examinations will
be performed including weight-bearing anterior-posterior views with knees flexed 30 degrees,
lateral, and sunrise views. The diagnosis of PFPS will be based on the subjects' being less
than 40 years of age, and the occurrence of chronic retropatellar pain in the absence of
other pain-causing abnormalities.

Arthrocentesis will be performed before all intra-articular injections, and any synovial
fluid collected will be visually inspected for signs of infection before performing any
injections. The volume of synovial fluid will be measured, and the samples will then be
retained for further biomarker analysis.

A follow-up visit will be scheduled approximately 3 months after the baseline visit, to
reevaluate patient condition.

Study Duration: A period of approximately 15 months is anticipated from the time the first
patient is enrolled to the completion of the last patient visit. A final study report will
then be generated after this 18 month time point.

Inclusion Criteria:

- Adults from the ages of 18-40, male or female

- Diagnosis of unilateral OR bilateral patellofemoral pain syndrome

- Duration of diagnosis no less than 2 months and no greater than 3 years in the study
knee

- Unresponsive to standard treatment of at least 6 weeks duration, consisting of
physical therapy, activity modification (relative rest), and/or oral analgesic therapy

- Insidious onset of symptoms unrelated to a traumatic incident

- Pain described as "behind", "underneath", or "around" the patella reported during at
least two of the following activities:

- Going up or down stairs

- Squatting

- Running

- Hopping or jumping

- Kneeling

- Prolonged sitting

- A baseline activity related VAS pain score between 50 and 90

Exclusion Criteria:

- Any co-morbidity that would influence the safety of intra-articular injections or
impede safety and efficacy measurements in the study knee, such as:

- Coagulopathies or the use of anticoagulant medications

- History of allergy to any of the treatment interventions planned

- Acute inflammation and/or palpable effusion in the study knee

- Current or history of musculoskeletal infection in the study knee

- Severe malalignment, deformity or chronic subluxation of study knee

- History of prior patellar dislocation of the study knee

- Ipsilateral joint/limb conditions (e.g. hip, thigh, lower leg, ankle, foot)

- Any condition other than PFPS in the contralateral knee present at the time of
enrollment or developing during the course of enrollment

- Any radiographic signs of the following:

- Osteoarthritis in any of the study knee compartments

- Osteochondritis dissecans (OCD) lesions

- Physeal injuries

- Bone tumors

- Vulnerable subjects and pregnant women

- Participation in any other musculoskeletal studies