Clinical trial: Intra-articular PVA Hydrogel in Knee Osteoarthritis (NCT04693104)

Eligibility criteria:
Inclusion Criteria:

          1. Signed and dated informed consent obtained before undergoing any
             clinical-investigation-related procedure.

          2. Male or female aged between 40 and 80 years.

          3. Documented diagnosis of primary OA of the knee, based on the clinical and radiological
             American College of Rheumatology (ACR) criteria for knee OA:

               -  Knee pain,

               -  X-ray osteophytes,

               -  at least one of the following: (a) age >50 years; (b) morning stiffness <30
                  minutes in duration; (c) crepitus on active motion.

          4. Grade II-III according to the Kellgren and Lawrence classification (X-ray evidence at
             enrolment or within the previous 12 months).

          5. Knee OA symptoms for at least six months.

          6. Failure to respond (i.e. did not respond sufficiently) to analgesics and/or regular
             NSAIDs, or proven intolerance to regular use of NSAIDs or to weak opioids analgesics.

          7. Presence of pain in the target knee, with a value ≥4 and ≤9 on the NRS, providing that
             pain in the contralateral knee I less than 3 (see also Exclusion Criteria n. 3).

          8. Ability and willingness to communicate, participate, and comply with the requirements
             and scheduled procedures of the clinical investigation.

        Exclusion Criteria:

        (a) Medical history and Concomitant Diseases related criteria

          1. Presence of isolated or predominantly symptomatic patellofemoral OA of the knee (i.e.
             pain when climbing stairs or forcing the patient to extend his leg when sitting on a
             low sit).

          2. Presence of secondary osteoarthritis and/or other rheumatic diseases. In particular,
             history or presence of the following diseases should be excluded: septic arthritis,
             inflammatory joint disease, gout, recurrent episodes of pseudogout, Paget's disease of
             bone, articular fracture, ochronosis, acromegaly, haemocromatosis, Wilson's disease,
             primary osteochondromatosis.

          3. Contralateral (i.e. non-target) knee pain >3 on the NRS

          4. Any knee OA treatment for both knees (other than the clinical investigation
             viscosupplementation of the target knee) anticipated within the next 6 months.

          5. Presence of pain (any severity) in the ipsilateral and/or contralateral hip.

          6. Presence of disease of the spine or other lower extremity joints of sufficient
             severity to affect the clinical investigation assessments.

          7. Anterior cruciate ligament repair, reconstruction or injury in the target knee within
             the previous 3 years.

          8. Cartilage repair/surgery in the target knee within the previous 3 years.

          9. Any surgery in the lower limbs within the previous 12 months

         10. Any planned surgery of the lower limbs during the clinical investigation period.

         11. Significant articular deformities of the lower limbs, i.e. major dysplasia and
             congenital abnormalities.

         12. Presence of varus or valgus knee deformity ≥ 8°.

         13. History or presence of osteonecrosis in the lower limbs.

         14. Presence of any significant injury of the ipsilateral limb within the previous 6
             months.

         15. Presence of joint effusion and/or infection at the target knee.

         16. Presence of local skin abnormalities (e.g. infection or disease) at the target knee.

         17. History or presence of knee joint infection secondary to previous intra-articular
             injections, or increased predisposition to infections.

         18. History or high risk of venous thromboembolism and/or venous or lymphatic stasis of
             the limb of the target knee.

         19. History of allergy or known hypersensitivity to hyaluronic acid, to any of the
             components of the products under clinical investigation, or to paracetamol.

         20. History of hypersensitivity to avian proteins.

         21. Morbidly obese patients (BMI≥35).

         22. Severe concomitant disease at any organ or apparatus (including acute or chronic
             infectious diseases) that may interfere with the free use and evaluation of the
             affected knee for the 6 months course of the clinical investigation and/or malignancy
             (with the exception of adequately treated or excised non metastatic basal cell or
             squamous cell cancer of the skin or in situ uterine cervical cancer) active within the
             previous 12 months.

         23. History of drug, alcohol, or other substance abuse, or other factors limiting the
             ability to cooperate during the clinical investigation.

         24. Any other clinically relevant disease and condition that, in the opinion of the
             principal investigators, may jeopardize the clinical investigation conduct according
             to the CIP or performance or safety assessments or may compromise the patients' safety
             or may place the patient at an undue risk by participating in the clinical
             investigation.

             (b) Previous or concomitant treatments

         25. Patients requiring systemic analgesics (including opiates)/NSAIDs for the target knee,
             or for indications other than OA pain at the target knee but likely to use these
             medications for more than 5 consecutive days, or for more than 10 non-consecutive days
             in one month, or unable to stop them during the 2 days preceding a clinic visit.

         26. Patients requiring topical analgesics/NSAIDs for the target knee.

         27. Patient requiring intra-articular corticosteroids into any joint or periarticular
             structure in the lower limb, or systemic corticosteroids (oral or injected for any
             indication).

         28. Patients who underwent tidal lavage of the knee joint(s) during the three months prior
             to randomization.

         29. Viscosupplementation in the lower limbs within the previous 12 months.

         30. Patients on SYSADOAs or a dietary supplement containing compounds considered specific
             for OA (e.g. glucosamine, chondroitin sulphate, diacerein) if the dosage has not been
             stable within the previous 3 months.

         31. Patients on anticoagulant treatment other than direct oral anticoagulants (DOACS).

         32. Non-pharmacological therapy for the lower extremities, unless stable for more than one
             month (and not to be substantially altered during the clinical investigation).
             Physical therapy is allowed.

         33. Patients using assistive devices other than a cane (walking stick) or knee brace.

         34. Concomitant participation in any clinical study/investigation or treatment with any
             investigational drugs/treatments/devices within the previous 3 months or 5 of
             half-lives (whichever is longer).

         35. Contraindication to use of hyaluronic acid.

         36. Contraindication to use of paracetamol. (c) Other

         37. For women of childbearing potential, not surgically sterile or postmenopausal:

               -  Pregnancy (i.e. positive pregnancy test at screening) or breastfeeding;

               -  Failure to agree to practice a highly effective method of contraception for 3
                  months after the IA injection.

         38. For sexually active men with a female partner of childbearing potential: failure to
             use a reliable method of birth control for 3 months after the IA injection.

        Randomization Criteria:

          1. Pain value in the target knee ≥4 and ≤9 on the NRS.

          2. Absence of joint effusion in the target knee.

          3. Absence of local skin abnormalities (e.g. infection or disease) at the target knee.

          4. No use of analgesics/NSAIDs during the 2 days preceding the Randomization Visit.
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 80 Years

Patient description (medical language): A 66-year-old woman comes to the office due to joint pain in the hands and periodic morning stiffness that lasts less than 15 minutes.  The pain is moderately severe and worsens with daily activity. The patient used Tylenol with minimal relief.  Past medical history is notable for hypertension and hypercholesteremia.  Physical examination shows firm nodules over the distal interphalangeal joints, bilaterally. The patient has pain in her knees as well. The knees are stiff in the morning for less than 30 minutes and become worse with climbing stairs. She has some sensation of bone friction during activity. X-ray shows narrowing of the joint space, subchondral bone sclerosis and osteophyte formation along the joints.

Patient description (patient's own words): I'm a 66-year-old woman and I went to my doctor's office because of a bloody joint pain in my hands that has been lasting for a while. The pain comes and go in the morning usually. I feel like a stiffness that last less than 15 minutes. The pain is moderately severe but it gets worse when I'm using my hands. I used Tylenol which helped a little. Apart from that, I suffer from hypertension and high cholesterol. The doctor made me notice that I have bumps around both of my hand joints. I also suffer from my knees and they are also stiff in the morning for around 30 min. It's even worse when I climb up the stairs! I also feel like my bones are rubbing against each other when I'm moving. The X-ray showed that I have narrow joint space, I have sclerosis, and abnormal growths of bone along my joints.

Does the patient match the trial criteria? 1