The Effect of Intra-articular Bilateral Knee Injections of Zilretta on Performance Measures in Adults With Knee OA

This study will be an open-label trial to determine the functional effects of bilateral IA
injections of Zilretta into knee joints of 70 subjects with bilateral KL grade 2-4
symptomatic knee osteoarthritis (OA). Measurement and evaluation of outcomes at baseline, 6,
12 and 24 weeks will allow assessment of short and long-term effects, consistent with
Osteoarthritis Research Society International (OARSI) and Outcome Measures in Rheumatology
(OMERACT) recommendations.

Eligibility Criteria

Inclusion Criteria:

- Men and women age 30 years or older with symptomatic bilateral knee OA

- Symptomatic knee OA will be defined as the presence of a definite osteophyte or joint
space narrowing (KL Grade ≥2) on posteroanterior (PA) fixed flexion knee radiographs
in subjects limited by bilateral pain rated on a Numerical Rating Scale as ≥ 4/10 on
more than half of the days over the past month. Radiographic change must be visible at
standard image size, irrespective of capability to detect more subtle changes through
digital enhancement

- Bilateral knee symptoms for ≥ 3 months prior to screening

- Has undergone at least one prior conservative osteoarthritis treatment (e.g. Physical
therapy, analgesics)

- Body Mass Index ≤ 40 kg/m2

- Ambulatory

- Willing and able to comply with the study procedures and visit schedules and ability
to follow verbal and written instructions

- Willingness to abstain from the use of protocol-restricted medications during the
study after signing informed consent and also willing to abstain from use of all
analgesics other than acetaminophen 1 week prior to beginning of the study

Exclusion Criteria

- Current consumption of more than 14 alcoholic drinks per week

- Clinical signs and symptoms of active knee infection or crystal disease of either knee
within 1 month of screening

- Diagnosed with rheumatoid arthritis, Reiter's syndrome, psoriatic arthritis, gout,
ankylosing spondylitis, or arthritis secondary to other inflammatory diseases; HIV,
viral hepatitis; chondrocalcinosis, Paget's disease, or villonodular synovitis

- Diagnosed with leukemia, known presence of metastatic malignant cells, or ongoing or
planned chemotherapeutic treatment

- Diseases of the spine, hip or other lower extremity joints judged by the investigator
to be contributing to the pain in either knee (i.e. sciatica, nerve pain, hip OA).
Note: Patients with hip replacement in either hip may be enrolled provided there is
sufficient pain relief after hip replacement that analgesics are not required

- Untreated symptomatic injury of either knee (e.g., acute traumatic injury, anterior
cruciate ligament injury, clinically symptomatic meniscus injury characterized by a
mechanical issue such as locking or catching)

- Uncontrolled diabetes (HbA1c >7.2)

- Women who report pregnancy or childbearing potential and not using acceptable
contraceptive measures (oral contraceptive, long acting reversible contraceptive
therapy) (due to the potential for change in body mass and distribution to alter knee
symptoms over the period of follow-up).

- Presence of surgical hardware or other foreign body intended to treat arthritis or
cartilage-related pathology in either knee

- Arthroscopy or open surgery of either knee within 6 months of screening

- Planned/anticipated surgery of either knee during the study period

- Use of systemic immunosuppressant within 6 weeks of screening

- Oral corticosteroids (investigational or marketed) within 2 weeks of screening (unless
on chronic stable dose for >3 months)

- IA corticosteroid (investigational or marketed) in either knee within 3 months of

- Corticosteroid injection (investigational or marketed) within 3 months of screening

- Any other IA drug/biologic use within 6 months of screening or 5 half-lives (whichever
is longer) (e.g., hyaluronic acid, platelet-rich plasma (PRP) injection, stem cells,
prolotherapy and amniotic fluid injection)

- Any documented clinically significant degree of cognitive impairment or other
condition, finding, or psychiatric illness at screening which, in the opinion of the
investigator, could compromise patient safety

- Any condition other than OA of the knee which, in the opinion of the investigator,
affects the ability to ambulate to a sufficient degree to interfere with the
assessment of the safety and treatment effects of the study injection

- Participated in any interventional drug or device trial within 30 days prior to
screening or concurrent participation in another research study that could complicate
interpretation of the study findings

Principal Investigator

Neil A Segal, MD

Study Contact

Jennifer Bedard,, 913-574-0961

Estimated Completion Date

Wednesday, June 10, 2020 #