Inclusion Criteria:
* 1\. Voluntarily given informed consent to investigation participation in writing encompassing 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 of Rheumatology (ACR) clinical and radiographic criteria for OA of the knee, and meeting the following conditions:
1. Non-severe Grade 2 to 3 osteoarthritis of the knee according to the Kellgren-Lawrence (KL) classification, confirmed by an extension face X-rays shot, supported by flexion face X-rays shot (optional) obtained within 6 months from the screening visit.
2. Subjects suffering from OA symptoms of the target knee for at least 6 months prior to the screening visit.
* 4\. Pain during walking on flat ground in the target knee of at least 40 mm and maximum 80 mm on a 0-100 mm VAS at the baseline visit (Visit 2).
* 5\. Subjects in treatment failure of first line treatment with oral NSAIDS
* 6\. Women of childbearing potential must have a negative urine pregnancy test prior to each injection.
* 7\. Subject who is able to comply with the study requirements, at the Investigator\'s appreciation.
Exclusion Criteria:
\- 1. Pregnant and breastfeeding women
* 2\. Subject with bilateral OA of the knees is excluded if one of the following points is present on the non-targeted knee has:
* a visual analog scale (VAS) score greater than 30mm (\> 30mm),
* a KL score is greater than 2 (\>2)
* a dedicated pain relief medicine 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 the study: 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 or anaphylactic shock according to the investigator opinion.
* 5\. Subject with a known allergy or hypersensitivity to Hyaluronic Acid or bovine collagen.
* 6\. Subject with a past history of severe streptococcal disease or an active streptococcus infection according to the investigator opinion.
7\. Subject with an infections, inflammation or skin diseases in the area of the injection site.
8\. Subject with a disorder that may impact wound healing such as connective tissue or immunosuppressive disorder.
9\. Subject having received chemotherapy agents, immunosuppressive medications within the past 3 months.
10\. Subject with bleeding disorders or subject having received medication (anti-platelet agents and anticoagulant) that will likely increase the risk of bleeding within the past 24 hours before injections.
11\. Subjects having received:
1. Intra-articular steroid injections within 60 days of the baseline visit or during study participation. Oral corticosteroids within four weeks of the screening visit or during study participation.
2. Chondroitinsulphate, glucosamine sulphate, diacereine, bisphosphonates or matrix metalloproteinase (MMP) inhibitors within 30 days prior to the baseline visit.
3. Viscosupplementation of the target knee within 6 months prior to the baseline visit.
4. Any kind of pain relief medicine and NSAIDs in the 24 hours prior to the baseline visit (V2).
12\. Subjects with a KL grade 4 patellofemoral osteoarthritis or subjects with a patellofemoral osteoarthritis KL grade higher than the femora-tibial one.
13\. Subjects with coxarthrosis. 14. Subjects having had any previous surgery in the target knee within 6 months prior to the screening visit, or any planned surgery in the target knee throughout the duration of the investigation.
15\. Subjects who have had arthroplasty at the target knee at any time. 16. Subjects having had diagnostic or surgical knee arthroscopy, or knee lavage in the target knee in the 6 months prior to the screening visit.
17\. Subjects that are candidate for knee replacement within the study period. 18. Subjects with body mass index (BMI) \> 35 kg/m2. 19. Subjects with large intra-articular effusion of the target knee, venous or lymphatic stasis, inflammatory flare-up with various symptoms, local inflammation.
20\. Subjects with history of septic OA of any joint 21. Subjects with significant pain outside the target knee, including significant hip or back pain and with fibromyalgia.
22\. Subjects with clinically significant valgus/varus deformities, ligamentous laxity, or meniscal instability as assessed by the Investigator.
23\. Subjects with other musculoskeletal condition affecting the target knee that would impair assessment of the effectiveness in the target knee (e.g. Paget's disease of bone).
24\. Subjects with a current malignancy or having treatment for a malignancy, except non-melanoma skin cancer.
25\. Subjects with drug or alcohol abuse 26. Subject who is deprived of their freedom by administrative or legal decision.
27\. Subject living in a social or sanitary establishment. 28. Subject being in an exclusion period for a previous study or with a current or recent (\<3 months) participation in another investigational study involving a drug or combined device with drug.
29\. Other condition preventing the subject to participate the study in the Investigator's opinion: subject deemed unreliable or incapable of understanding and complying with the study assessment or unrealistic expectations of treatment results.
