Knee OsteoArthritis Long-term Assessment

Randomized Controlled Single-Blind Multi-Centre Evaluation of the Safety and Performance of an Injection of Hydrogel OA 2% in Subjects With Knee Osteoarthritis

The goal of this clinical study is to learn if Hydrogel OA 2% injection is safe and whether it works to improve symptoms of diagnosed knee osteoarthritis in adults when compared to Hyaluronic Acid (Durolane), a treatment that is currently often used for treatment of knee osteoarthritis. The main question it aims to answer is:

- How many study participants will experience side effects related to Hydrogel OA 2% during the study when compared to Hyaluronic Acid (Durolane)?

All study participants will receive either one Hydrogel OA 2% or Hyaluronic Acid (Durolane) injection in their knee during the clinical study. Study participants will not know which treatment they have received. Study participants will also receive a call from the researchers and visit the clinic three times to report whether they have experienced any side effects, and complete a questionnaire that will ask questions on whether their symptoms have improved since they received an injection.

Inclusion Criteria:

• Adults accepting to participate in the study and having signed the written informed consent form before any protocol-specific procedures and able to understand and follow the instructions as described in the protocol.
• Unilateral symptomatic tibiofemoral KOA confirmed by a "standing knee" X-ray. In case of bilateral KOA on X-ray only one knee (indexed knee) presents symptomatic OA pain.
• Age 35 ≤ 75 years.
• BMI 20 ≤ 35.
• Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain score 25-85.
• Radiological Kellgren and Lawrence (K&L) grade II and III from a standing knee radiograph with minimum joint space of 1 mm in the study knee.
• Fully ambulatory for functional assessments.
• Willingness to refrain from taking any pain medication for 48 hours prior to each study visit.
• Female subjects must be on effective contraception (pill, patch, ring, diaphragm, implant or intrauterine device), if not surgically sterile (tubal ligation or hysterectomy) or postmenopausal for at least one year. Females must show a negative pregnancy test at the treatment visit.

Exclusion Criteria:

• Bilateral tibiofemoral KOA where the non-symptomatic knee presents worse radiological grade of KOA.
• Radiological K&L grade 0, I, or IV from a standing knee radiograph assessed during the screening visit, using the most recent x-ray taken either immediately or within the past 3 months. Significant clinically assessed varus or valgus deformation of the selected knee side of more than 10 degrees.
• Extension deficit of the index knee of higher than 5 degrees.
• Bilateral symptomatic tibiofemoral KOA or a combined unilateral symptomatic tibiofemoral knee and hip OA.
• Clinical signs of significant effusion with noticeable swelling and/or inflammation related severe pain during the treatment visit.
• Evidence of active lymphatic or venous stasis or serious blood disorders (e.g., anemia), bleeding disorders (e.g., hemophilia), blood clots, or blood cancers (e.g., leukemia, lymphoma, and myeloma).
• Active bacterial infection, resulting in hospitalization and/or requiring intravenous antibiotic treatment.
• Synovial infection, skin infections or any skin diseases in the area of the injection site.
• History of autoimmune diseases that cause chronic joint pain and inflammation in the knee joint, including rheumatoid arthritis, psoriasis arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, gout, pseudogout, systemic sclerosis, Sjögren's disease, adult-onset still's disease.
• Known or suspected generalized chronic pain disorder.
• Severe alteration of mobility preventing any functional assessment.
• Allergy or hypersensitivity to any of the product components.
• Conditions (orthopedic, rheumatologic, musculoskeletal or inflammatory) causing symptomatic and/or radiating pain in the lower extremities that might interfere with the symptomatic OA knee pain, including hip OA assessed by physical examination by the physician.
• Symptomatic patellofemoral knee OA.
• Oral corticotherapy ≥4 mg/day (in prednisone equivalent) in the last 3 months before injection.
• Severe acute illness within 14 days prior to investigational device administration.

Any intra-articular injection (hyaluronan, hydrogel, soft implant, corticosteroid, platelet-rich plasma, local anesthetic etc.) arthroscopy, surgery in the treated knee; or cell-based therapy or an invasive procedure on the treated knee in the last 6 months before screening visit.

• Anticipated need for any surgical or other invasive procedure throughout the course of the clinical investigation, including prosthesis in the treatment knee, any concurrent OA treatments including alternative treatments (e.g., acupuncture, ultrasound, magnetic resonance etc.).
• Any investigator-assessed clinically significant condition that may represent a substantial risk to the patient or may have an impact on the study assessments.
• Participation in another clinical trial in the last 3 months before injection.
• Pregnancy and breastfeeding.
• Legal incapacity or limited legal capacity to consent.
• Trauma of the treatment knee in the last 6 months before the treatment visit.