safety performance chitosan osteoarthritis viscosupplementation

Conditions: Knee Osteoarthritis

Summary: kio014 is an innovative chitosan-based biomaterial intended for synovial fluid viscosupplementation indicated for the symptomatic treatment of knee osteoarthritis (oa). the study kio014-aproove is aimed to evaluate the safety and performance of kio014 in patients with symptomatic knee oa. a total of 100 patients will be enrolled. the study is divided in two stages. the stage 1 cohort is the safety cohort where 10 patients will be enrolled. stage 1 patients receiving two injections of kio014 at day 0 and at month 3, and will be followed for 12 months post initial injection. the stage 2 cohort is the performance cohort for 90 patients, and this stage will be randomized controlled and single-blind for the patient. in stage 2, 60 patients will receive an intra-articular injection of kio014 (test group) and 30 patients will receive an intra-articular injection of durolane® (control group). patients will be followed for 6 months.


Eligibility criteria:
inclusion criteria: * male or female with age ≥ 40 years and ≤ 85 years except in stage 1 cohort where age is limited to ≤ 70 years. * body mass index (bmi) ≤ 35 kg/m². * uni- or bilateral femorotibial knee oa associated or not with femoropatellar knee oa. * primary knee osteoarthritis responding to the clinical and radiological criteria of the american college of rheumatology (acr) * radiological kellgren and lawrence (k\&l) grade ii to iii from a standing knee radiograph taken less than 6 months previously. * symptomatic pain at least 6 months in the treatment knee not or poorly responding to first line non-opioid analgesics and non-steroidal anti-inflammatory drug in oral uptake. * pain criteria assessed prior to injection at visit 1 after mandatory 48-hour wash-out: * treatment knee: 7-17 points of the 5-graded likert womac pain score and at least 2 points on the womac pain subscore a1 in the most affected knee. * non-treatment knee: not more than 6 points of the 5-graded likert womac pain score in the contralateral knee. * fully ambulatory patient for functional evaluation * willing not to take any pain medication for 48 hours prior to study visit. * for female not surgically sterile (tubal ligation or hysterectomy) or not postmenopausal for at least one year, must have an effective contraception (pill, patch, ring, diaphragm, implant and intrauterine device). * able to understand and follow the instructions of the study. * having signed a written informed consent. exclusion criteria: * related to the oa pathology and related symptoms: * radiological k\&l grade 0, i or iv from a standing knee radiograph taken less than 6 months previously. * exclusively patellofemoral osteoarthritis where the symptoms, including pain, are principally of patellofemoral origin (patellar syndrome). * chondromatosis or villonodular synovitis of the knee. * clinically-apparent knee effusion, inflammation or flare-up of the knee or abnormal synovial fluid macroscopy or volume upon arthrocentesis on the day of injection. * history of injury to the treatment knee during the 6 months before inclusion or recent trauma (\<1 month) of the knee responsible of pain that is not directly related to oa symptoms. * significant clinically-assessed or radiographic varus or valgus deformation of the selected knee at the judgment of the investigator. * inflammatory disease. * pathologies interfering with the evaluation of oa pain for the knee to be treated. * related to treatments: * contraindications: hypersensitivity or allergy to the product components of kio014, including chitosan, sorbitol and/or other mushroom-derived products, or to hyaluronic acid-based products. * corticosteroids or plasma rich platelet (prp) or cell-based therapy injection in the treatment knee in the last 3 months before injection. * hyaluronic acid injection in the treatment knee in the last 6 months before injection. * arthroscopy and surgery in the treatment knee in the last 6 months before injection. * oral corticotherapy ≥5 mg/day (in prednisone equivalent) in the last 3 months before injection. * change in the dosage regimen of symptomatic slow-acting drugs (sysad) or dietary supplement in the last 3 months before injection. * change in physiotherapy of the treatment knee in the last 3 months. * anticipated need for any surgical or other invasive procedure during the trial including prosthesis in the treatment knee. * anticipated need for any forbidden oa treatments during the trial except for rescue treatment as defined in the study protocol. * anticoagulants: coumarin-based compounds or heparin. * related to associated diseases: * any investigator-assessed clinically significant condition that may represent a substantial risk to the patient or may have an impact on the study assessments. * history of recurrent bacterial infection, defined as at least 3 major infections resulting in hospitalization and/or requiring intravenous antibiotic treatment within the past 2 years or history of synovial infection or infections or skin diseases in the area of the injection site. * history of symptomatic hip oa * history of autoimmune disease. * severe, ongoing and uncontrolled diseases, or other major disease, or other severe uncontrolled conditions. * subject addicted to alcohol or drugs or ongoing or recently recovered depression or psychiatric disorders or any other disorder and/or that may pose a health risk to the subject in the study and/or may have an impact on the study assessments. * severe alteration of mobility preventing any functional evaluation. * high risk of hemorrhage. * related to patients: * participation in a therapeutic clinical trial in the last 3 months before injection. * patient under guardianship or judicial protection. * pregnancy, breastfeeding, planned conception, or premenopausal women without effective contraception, tubal ligation or hysterectomy.