New Treatment of Knee Osteoarthritis

Pivotal clinical investigation, interventional, prospective, comparative, single-blinded, controlled with two arms, randomized, multicentre clinical trial designed to assess the performance and safety of ABIO3419 for the treatment of osteoarthritis of the knee.

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:

• 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.
• 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.

• Subject with an infections, inflammation or skin diseases in the area of the injection site.

• Subject with a disorder that may impact wound healing such as connective tissue or immunosuppressive disorder.

• Subject having received chemotherapy agents, immunosuppressive medications within the past 3 months.

• 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.

• Subjects having received:
• 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.
• Chondroitinsulphate, glucosamine sulphate, diacereine, bisphosphonates or matrix metalloproteinase (MMP) inhibitors within 30 days prior to the baseline visit.
• Viscosupplementation of the target knee within 6 months prior to the baseline visit.
• Any kind of pain relief medicine and NSAIDs in the 24 hours prior to the baseline visit (V2).

• Subjects with a KL grade 4 patellofemoral osteoarthritis or subjects with a patellofemoral osteoarthritis KL grade higher than the femora-tibial one.

• 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.

• 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.

• 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.

• 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.

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

• 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).

• Subjects with a current malignancy or having treatment for a malignancy, except non-melanoma skin cancer.

• Subjects with drug or alcohol abuse 26. Subject who is deprived of their freedom by administrative or legal decision.

• 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.

• 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.