The Effect of Intra-articular Bilateral Knee Injections of Zilretta on Performance Measures in Adults With Knee OA
Condition: Knee Osteoarthritis
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: Zilretta
Intervention description: Zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee osteoarthritis.
Intervention MeSH terms: Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: This will be an open-label study to determine the functional effects of IA injection of Zilretta into bilateral knees of 70 subjects with KL grade 2-4 symptomatic knee OA. Measurement of OARSI recommended physical performance measures, patient-reported physical function, quality of life and pain at baseline, 6, 12 and 24 weeks will allow assessment of short and long-term effects, consistent with OARSI and OMERACT recommendations
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No

Summary:

      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 ≤ 41 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 treatment.

        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.

          -  A gout attack in the past 2 years.

          -  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
             screening.

          -  IV or IM (Intramuscular) 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 subject 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.