Key Inclusion Criteria:
Male and female participants >= 50 and <= 80 years old on the day of Informed Consent signature.
Participants must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 35 kg/m2 at screening. BMI = Body weight (kg) / [Height (m)]2
High sensitivity C-reactive protein (hsCRP) >=2 mg/L at screening
Symptomatic OA with pain (Numeric Rating Scale [NRS] 5-9, inclusive) in the target knee for the majority of days in the last 3 months prior to screening
KOOS pain sub-scale score <= 60 in index knee at screening and baseline
Radiographic disease: K&L grade 2 or 3 knee osteoarthritis and joint space width 2-4 mm for males and 1.5-3.5 mm for females in the medial tibiofemoral compartment (TFC) in the target knee
Active synovial inflammation at screening, defined as either moderate (score 9-12) or severe (score >=13) based on contrast enhanced MRI (CE-MRI) of the whole knee for synovitis detection from 11 sites
Key Exclusion Criteria:
Total WBC count < 3,000/µL, absolute peripheral blood neutrophil count (ANC) < 1,000/µL, hemoglobin < 8.5 g/dL (85 g/L) or platelet count < 100,000/µL at Screening
Known autoimmune disease with inflammatory arthritis (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus), crystal-induced arthritis (gout, pseudogout associated arthritis), active acute or chronic infection or past infection of the knee joint, Lyme disease involving the knee, reactive arthritis, systemic cartilage disorders, moderate to severe fibromyalgia (widespread pain index, WPI, >4 out of 19), or a known systemic connective tissue disease
Any known active infections, including skin or knee infections or infections that may compromise the immune system, such as HIV or chronic hepatitis B or C infection. COVID-19 specific: PCR or antigen test against COVID-19 is mandatory where required by the local Health Authority and/or by local regulation, e.g. in Germany.
Use of prohibited medications: any local i.e. treatment into the knee, including but not restricted to viscosupplementation and corticosteroids within 12 weeks prior to Day 1; long-term treatment (>14 days) with oral corticosteroids >5 mg/day within 4 weeks prior to Day 1; oral glucosamine, chondroitin sulfate, or any nutraceutical with potential activity on cartilage repair within 2 weeks prior to Day 1; systemic Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or selective COX-2 inhibitors within 5 half-lives from PRO assessments; any other immunomodulatory drugs or treatment which cannot be discontinued or switched to a different medication within 28 days or 5 half-lives of screening (whichever is longer if required by local regulations), or until the expected PD effect has returned to baseline.
Contralateral knee pain >=4 by NRS for the majority of days in the last 3 months prior to Screening
Participants with the CYP2C9 *3/*3 genotype defined as homozygous carriers of the CYP2C9*3 allele.
Severe malalignment greater than 7.5 degrees in the target knee (either varus or valgus), measured using x-ray at Screening