Osteoarthritis (OA) is one of the most common diseases affecting the joints, usually those that are weight bearing such as the knees. OA is considered to be a disease of the cartilage in the joints even though it involves the whole joint, including the bone and synovium (thin lining of the joints which produces synovial fluid). With time, more and more of the cartilage is destroyed by the disease with inflammation commonly occurring.

AS902330 is expected to increase the production and development of specific bone cells: chondrocytes and osteoblasts (cells that produce and maintain bone and cartilage). This is expected to lead to repair and generation of the cartilage, and a narrowing of the space width between the knee joints in a selected region of the knee cartilage. The purpose of this study is to see how safe treatment with AS902330 is, and to evaluate its effect on the knee cartilage. In addition, the study will also measure the effects of AS902330 in the blood, which reflect disease activity.

Inclusion Criteria:

1. Male or female >= 40 years of age; females must be postmenopausal or surgically sterile
2. Established diagnosis of primary femoro-tibial OA of the target knee by standard American College of Rheumatology Criteria for at least six months (clinical AND radiological criteria)
3. Radiological disease stage 2 or 3 (i.e., clear evidence of OA, but not most advanced disease) in the target knee according to the Kellgren-Lawrence grading of knee OA
4. No major knee surgery (e.g., partial or total knee replacement, interventional arthroscopy) in the target knee planned for at least 12 months after first injection of the study drug
5. Documented need for symptomatic PRN (as needed)-treatment for OA in the target knee with systemic non-steroidal anti-inflammatory drugs (NSAIDs) and/or other analgesics.
6. Total WOMAC score between 24 and 72 (out of 96, corresponding to mild, moderate, or severe, but not extreme OA symptoms) for the target knee while on oral symptomatic treatment at baseline
7. Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
8. Patients must have read and understood the informed consent form, and must have signed it prior to any study-related procedure

Exclusion Criteria:

• any condition, including laboratory findings and findings in the medical history or in the pre-study assessments, that in the opinion of the Investigator constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation
• clinically significant abnormal hematology (hemoglobin, leucocytes, and platelets), or blood chemistry values (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, and creatinine
• receipt of any investigational product or any experimental therapeutic procedure within the last 12 weeks preceding screening
• participation in FIH study 27575 or in a different cohort of this study
• i.a. treatment of the target knee with steroids or hyaluronic acid derivatives within the 3 months before baseline
• for MAD cohorts, any contra-indications to MRI according to MRI guidelines
• any condition that would interfere with efficacy or safety assessments in the target knee
• any drug or food supplement with potential disease-modifying effect (glucosamine, diacerin, chondroitin sulfate) unless given at a stable dose over at least 4 weeks prior to first injection
• use of electrotherapy or acupuncture for OA, unless there is a stable regimen for at least 4 weeks before baseline
• any known active infections, including suspicion of intra-articular infection and/or infections that may compromise the immune system such as HIV, Hepatitis B or Hepatitis C infection
• history of sarcoma and/or of other active malignancy within five years, except adequately treated basal cell or squamous cell carcinoma of the skin
• signs and symptoms suggestive of transmissible spongiform encephalopathy
• secondary osteoarthritis: e.g., joint dysplasias, aseptic osteonecrosis, acromegaly, Paget's disease, Ehlers-Danlos syndrome, Gaucher's disease, Stickler's syndrome, joint infection, hemophilia, hemochromatosis, calcium pyrophosphate deposition disease, or neuropathic arthropathy whatever the cause