Study of Efficacy, Safety and Tolerability of DFV890 in Patients With Knee Osteoarthritis

Key Inclusion Criteria:

• Male and female participants >= 50 and <= 80 years old on the day of InformedConsent signature.

• Participants must weigh at least 50 kg to participate in the study, and must have abody mass index (BMI) within the range of 18 - 35 kg/m2 at screening. BMI = Bodyweight (kg) / [Height (m)]2

• High sensitivity C-reactive protein (hsCRP) >=1.8 mg/L at screening

• Symptomatic OA with pain (corresponding to Numeric Rating Scale [NRS] 5-9,inclusive) in the target knee for the majority of days in the last 3 months prior toscreening

• KOOS pain sub-scale score <= 60 in index knee at screening and baseline

• Radiographic disease: K&L grade 2 or 3 knee osteoarthritis in the target knee,confirmed by X-ray at screening.

• Active synovial inflammation at screening (defined a summary score of ≥7 with atleast one region scoring 2) on contrast enhanced MRI (CE-MRI) of the whole knee forsynovitis 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 torheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupuserythematosus), crystal-induced arthritis (gout, pseudogout associated arthritis),active acute or chronic infection or past infection of the knee joint, Lyme diseaseinvolving the knee, reactive arthritis, systemic cartilage disorders, moderate tosevere fibromyalgia (widespread pain index, WPI, >4 out of 19), or a known systemicconnective tissue disease

• Any known active infections, including skin or knee infections or infections thatmay 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 requiredby the local Health Authority and/or by local regulation, e.g. in Germany.

• Use of prohibited medications: any local i.a. treatment into the knee, including butnot restricted to viscosupplementation and corticosteroids within 12 weeks prior toDay 1; long-term treatment (>14 days) with oral corticosteroids >5 mg/day within 4weeks prior to Day 1; oral glucosamine, chondroitin sulfate, or any nutraceuticalwith potential activity on cartilage repairfrom screening 1; systemic Non-SteroidalAnti-Inflammatory Drugs (NSAIDs), selective Cyclooxygenase-2 (COX- 2) inhibitors orother non-opioid analgesics not defined as basic pain medication within 5 half-livesfrom PRO assessments; any other immunomodulatory drugs or treatment which cannot bediscontinued or switched to a different medication within 28 days or 5 half-lives ofscreening (whichever is longer if required by local regulations), or until theexpected PD effect has returned to baseline.

• Moderate to severe pain in the contralateral knee for the majority of days in thelast 3 months prior to Screening, as per patient judgment.

• Severe malalignment greater than 7.5 degrees in the target knee (either varus orvalgus), measured using x-ray at Screening.

Additional protocol-defined inclusion / exclusion criteria may apply.