Study on Knee Osteoarthritis

Inclusion Criteria:

1. Voluntarily given informed consent to investigation participation in writingencompassing consent to data recording and verification procedures.

2. Male and female subjects, aged 35 to 85 years (inclusive).

3. Subjects affected by knee osteoarthritis, as defined by American College ofRheumatology (ACR) clinical and radiographic criteria for osteoarthritis of theknee, and meeting the following conditions:

4. Kellgren-Lawrence Grade 2 to 3 severity osteoarthritis of the knee confirmed byan extension face X-rays shot, supported by flexion face X-rays shot (optional)obtained within 6 months from the screening visit.

5. Subjects suffering from osteoarthritis symptoms of the target knee for at least 6 months prior to the screening visit.

6. Pain during walking on flat ground in the target knee of at least 40 mm and maximum 80 mm on a 0-100 mm Visual Analogic Scale at the baseline visit (Visit 2).

7. Women of childbearing potential must have a negative urine pregnancy test prior toeach injection.

8. Subject who is able to comply with the study requirements, at the Investigator'sappreciation.

9. Subject being affiliated to a health social security system

Exclusion Criteria:

1. Pregnant and breastfeeding women

2. Subject with bilateral osteoarthritis of the knees is excluded if one of thefollowing point is present on the non-targeted knee has:

• a visual analog scale score greater than 30mm (> 30mm),

• a Kellgren-Lawrence score is greater than 2 (>2)

• a dedicated antalgic consumption.

3. Subject suffering from a severe or progressive disease or any other pathology which,according to the investigator, may interfere with evaluation of the results of thestudy: diabetes, autoimmune pathology, cardiac pathologies, hepatic deficiency,epilepsy, porphyria, rheumatoid arthritis or other systemic inflammatory process.

4. Subject who has a known history of severe multiple allergies, angioedema oranaphylactic shock according to the investigator opinion.

5. Subject with a known allergy or hypersensitivity to Hyaluronic Acid or bovinecollagen.

6. Subject with a past history of severe streptococcal disease or an activestreptococcus infection according to the investigator opinion.

7. Subject with a disorder that may impact wound healing such as connective tissue orimmunosuppressive disorder.

8. Subject having received chemotherapy agents, immunosuppressive medications withinthe past 3 months.

9. Subject with bleeding disorders or subject received medication (anti-platelet agentsand anticoagulant) that will likely increase the risk of bleeding within the past 24hours before injections.

10. Subjects having received:

11. Intra-articular knee corticosteroids within 60 days prior to the baselinevisit.

12. Chondroitinsulphate, glucosamine sulphate, diacereine, bisphosphonates ormatrix metalloproteinase inhibitors within 30 days prior to the baseline visit.

13. Viscosupplementation of the target knee within 6 months prior to the baselinevisit.

14. Any kind of antalgic and Non-steroidal anti-inflammatory drugs in the 24 hoursprior to the baseline visit (V2) and before each visit.

15. Subjects with a Kellgren-Lawrence grade 4 femora-patellar osteoarthritis or subjectswith a femora-patellar osteoarthritis Kellgren-Lawrence grade higher than thefemora-tibial one.

16. Subjects with coxarthrosis.

17. Subjects having had any previous surgery in the target knee within 6 months prior tothe screening visit, or any planned surgery in the target knee throughout theduration of the investigation.

18. Subjects who have had arthroplasty at the target knee at any time.

19. Subjects having had diagnostic or surgical knee arthroscopy, or knee lavage in thetarget knee in the 6 months prior to the screening visit.

20. Subjects that are candidate for knee replacement within next 6 months.

21. Subjects with body mass index > 35 kg/m2.

22. Subjects with large intra-articular effusion of the target knee, venous or lymphaticstasis, inflammatory flare-up with various symptoms, local inflammation.

23. Subjects with history of septic osteoarthritis of any joint

24. Subjects with significant pain outside the target knee, including significant hip orback pain and with fibromyalgia.

25. Subjects with clinically significant valgus/varus deformities, ligamentous laxity,or meniscal instability as assessed by the Investigator.

26. Subjects with other musculoskeletal condition affecting the target knee that wouldimpair assessment of the effectiveness in the target knee (e.g. Paget's disease ofbone).

27. Subjects with a current malignancy or having treatment for a malignancy, exceptnon-melanoma skin cancer.

28. Subjects with drug or alcohol abuse

29. Subject who is deprived of their freedom by administrative or legal decision.

30. Subject living in a social or sanitary establishment.

31. Subject being in an exclusion period for a previous study or with a current orrecent (<3 months) participation in another investigational study involving a drugor combined device with drug.

32. Other condition preventing the subject to participate the study in theInvestigator's opinion: subject deemed unreliable or incapable of understanding andcomplying with the study assessment or unrealistic expectations of treatmentresults.