The study will be conducted in participants with symptomatic knee OA to explore the safety, tolerability, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of MAD of M6495.

Inclusion Criteria:

• Kellgren Lawrence (KL) radiological Grade of 2 to 4 in the target knee
• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore of greater than or equal to (>=) 40 out of 100 in the target knee at screening
• Primary or post-traumatic femorotibial OA according to American College of Rheumatology clinical and radiographic criteria
• Have completed at least 4 days of the participant 7-day diary in the period from Day -8 to Day 1
• Can give signed informed consent
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• History of arthroscopy or intra-articular administration of corticosteroids or hyaluronic acid into the target knee within 6 months before screening
• Intention of having major knee surgeries or total knee replacement during the time frame of this study in either knee
• Secondary OA in target knee joint because of joint dysplasia, aseptic osteonecrosis, acromegaly, Paget disease, Stickler syndrome, hemochromatosis, gout, chondrocalcinosis, or calcium pyrophosphate deposition disease
• Any known active systemic infection, including infection that might compromise the immune system such as human immunodeficiency virus, or hepatitis B or C
• History of myocardial infarction or cerebrovascular event within 6 months prior to screening, or current active angina pectoris, symptomatic heart failure, seizures, untreated hypertension, gastrointestinal bleeding, or any other significant medical condition in the Investigator's opinion
• History of cancer, except adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix, unless considered cured >= 5 years
• Other protocol defined exclusion criteria could apply