Inclusion Criteria: * Subjects must be willing and able to comply with the study procedures and visit schedule and able to follow verbal and written instructions. * Subjects must be male or female and 45 to 80 years old, inclusive, at Screening. * Subjects must exhibit symptoms associated with osteoarthritis of the index knee for ≥12 months before Screening (subject self-reporting is acceptable). * Subjects must have index knee pain for \>15 days over the last month before Screening (subject self-reporting is acceptable). * Subjects must have failed 2 or more therapies: Restricted physical activity as per Osteoarthritis Research Society International (OARSI) core level recommendation, ie, "structured land-based exercise" (this may include physical therapy), and failure of an additional type of conservative therapy for OA of the index knee, eg, nonselective NSAIDs or COX-2 inhibitors, in the past 12 months. * Subjects must have a body mass index (BMI) ≤40 kg/m2 at Screening. * Subjects must have an index knee examination indicating the index knee and the intended injection site area are free of any signs of local or joint infection at Baseline. * Subjects must have an index knee Average Daily Knee Pain (NRS) between ≥5.0 and ≤9.0 at Screening and Baseline. * Sexually active subjects of child-bearing potential (SOCBP) and their partners must agree to use effective birth control while in the study * Subjects must have active synovitis in the index knee as determined by ultrasound Doppler. * Subjects must exhibit American College of Rheumatology Criteria (clinical and radiological) for osteoarthritis as follows: 1. Knee pain 2. At least 1 of the following: i. Age \>50 years ii. Morning stiffness \<30 minutes iii. Crepitus on knee motion c. Osteophytes * Subjects must have K-L Grade 2, 3, or 4 in the index knee based on X-rays performed during Screening and confirmed by trained radiographers at a central facility before enrollment * Subjects need to show the presence of moderate or severe synovitis based on 11-point synovitis score using contrast-enhanced MRI Exclusion Criteria: * Subjects have any current or prior diagnosis of autoimmune connective tissue disorders, secondary OA conditions, benign synovial tumors, gout/pseudogout, reactive arthritis, RA, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease. * Subjects have any active systemic or local infection, including infection of the index knee * Subjects are unable to undergo MRI with contrast MRI * Subjects with X-ray or MRI exclusionary events * Subjects have an unstable index knee joint (eg, torn anterior cruciate ligament) within 12 months of Screening * Subjects have used any approved or investigational IA drug/biologic in index knee within 6 months of Screening (eg, hyaluronic acid, platelet rich plasma, stem cells, prolotherapy, and amniotic fluid injection) * Subjects are receiving or have received any gene therapy treatment (eg, IL-1Ra) in the past 3 years * Subjects have used IA steroids ≤3 months before screening Other protocol-defined criteria apply