Clinical trial: sAfety PerfoRmance chitOsan osteOarthritis ViscosupplEmentation (NCT03679208)

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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 40 Years old.
Subject must be at most 85 Years

Patient description (medical language): A 47-year-old woman comes to the office complaining of pain in the calf and knee when she bends down. The pain limits her activity. Her medical history is significant for osteoarthritis, for which she uses nonsteroidal anti-inflammatory drugs (NSAIDs) for the past two years. She is living with her husband and has 3 children. She doesn't smoke but drinks alcohol occasionally. Her vital signs are normal. On physical examination, there is a small effusion in the right knee. The effusion grew a little larger and she developed a tender swelling in the popliteal fossa and calf. Both the pain and swelling worsened as she bent and straightened her knee.

Patient description (patient's own words): I'm a 47-year-old woman, married with 3 kids. I don't smoke and I drink occasionally. I went to the doctor because of pain in my calf and knee when I was bending down. This has been limiting my daily activities. I have been diagnosed with osteoarthritis for which I have taken anti-inflammatory drugs for the past 2 years. The doctor saw a small fluid buildup in my right knee. This buildup became a bit bigger and I have a swollen calf. The pain is worse when I bend and straighten my knee.

Does the patient match the trial criteria? Entailment