Clinical trial: Phase III Study on the Safety and Efficacy of a Single Intra-articular Administration of JTA-004 in Symptomatic Knee Osteoarthritis (NCT04333160)

Eligibility criteria:
Inclusion Criteria:

          -  Ambulatory (able to walk unassisted, the use of a crutch or a walking stick (only one)
             is allowed if already used at screening but should be avoided during the study up to
             the 6-month follow-up visit)

          -  Diagnosed with primary knee OA, fulfilling the following American College of
             Rheumatology (ACR) criteria at the target knee:

               -  Pain present for most days of the preceding month

               -  Morning stiffness < 30 minutes

               -  Kellgren-Lawrence grade II or III (confirmed by appropriate X-rays taken within 6
                  months prior to screening visit)

          -  Target knee pain ≥ 200 mm and ≤ 400 mm out of 500 mm on the WOMAC® VA3.1 pain
             questionnaire (sum of 5 questions) at screening and baseline

          -  Insufficient/failed response or intolerance to analgesics and/or non-steroidal
             anti-inflammatory drugs (NSAIDs) as reported by the subject

          -  Willing and able to abstain from initiation of physical therapy and of use of knee
             braces at the target knee up to the 6-month follow-up visit (a subject undergoing
             physical therapy or using knee braces at a stable frequency for at least 2 weeks prior
             to screening is allowed to continue at same frequency (frequency increase is not
             allowed))

          -  Capable to understand and comply with study requirements and to provide a written,
             dated, and signed informed consent prior to any study procedure for participation in
             the study and transmission of personal "pseudo-anonymized" data

        Exclusion Criteria:

          1. History of trauma or surgery or arthroscopy at the target knee within 12 months before
             inclusion

          2. Concomitant inflammatory disease or other conditions affecting the joints (e.g.,
             infectious arthritis, rheumatoid arthritis, psoriatic arthritis or
             spondyloarthropathy, Paget's disease, hemochromatosis…)

          3. Any target knee abnormality that could impact safety or efficacy assessment

          4. Microcrystalline arthropathies: chondrocalcinosis/calcium pyrophosphate dihydrate
             disease (pseudo-gout) or gout if believed likely to interfere with the study
             endpoints, in the opinion of the Investigator

          5. Clinically significant valgus/varus deformities at the Investigator's discretion

          6. Any musculoskeletal condition (such as symptomatic hip OA, amputation, neurologic
             disorder, chronic back pain with or without radiculopathy, sciatica) that would impede
             measurement of efficacy at target knee

          7. Contralateral knee pain equal to or exceeding the pain in the target knee (on the
             WOMAC® VA3.1 pain questionnaire) at screening and/or baseline

          8. Knee arthroplasty planned within 12 months after the screening visit Current or
             previous diagnoses, signs and/or symptoms

          9. Uncontrolled diabetes mellitus (hemoglobin A1c [HbA1c] > 10% or > 86 mmol/mol),
             end-stage hepatic or renal disease (severe and clinically significant abnormalities
             according to local laboratory ranges) documented in the subject's file

         10. Any relevant cardiovascular disease (severe coronary insufficiency, conduction
             disturbances, recent myocardial infarction, cerebrovascular disease) or any clinically
             significant electrocardiogram (ECG) abnormality as judged by the Investigator

         11. Subject with neuropathic pain or chronic pain syndrome including fibromyalgia

         12. Current (or within the last 5 years prior to entering the study) history of solid or
             hematological neoplasia or bone marrow transplantation (except for basal cell
             carcinoma and completely excised squamous cell carcinoma)

         13. Other severe acute or chronic medical or psychiatric conditions or pre-dispositions or
             laboratory abnormalities, as judged by the Investigator

         14. Current or past history of coagulation disorders (according to local laboratory
             ranges), as judged by the Investigator

         15. Hypersensitivity to any components of hyaluronic acid (HA)-based injection products

         16. Hypersensitivity to human biological material including blood and blood-derived
             products, potential excipients and residues from manufacturing process, documented
             clinically or by laboratory tests

         17. Hypersensitivity to avian proteins Current or previous treatment

         18. Participation in another clinical trial within 3 months prior to screening (within 1
             year prior to screening if disease-modifying OA drug (DMOAD) received and if the
             Investigator considers it could impact the safety or efficacy assessment)

         19. Subject previously treated with JTA-004 within 2 years prior to screening

         20. Subject treated with intra-articular viscosupplement or blood-derived product (e.g.,
             platelet-rich plasma) injection in the target knee within 6 months prior to screening

         21. Subject treated with intra-articular glucocorticoid injection in the target knee
             within 4 months prior to screening

         22. Subject having started the use of slow acting drugs for OA such as glucosamine,
             glucosamine sulfate, chondroitin sulfate, diacerein, curcumin, soybean/avocado
             extracts or related products within 1 month prior to screening

         23. Current chemo-, radio- or immuno-cancer-therapy or immunosuppressive therapy

         24. Chronic (≥ 3 days/week within the last 3 months) use of opioids other than weak
             opioids (such as codeine, dihydrocodeine, tramadol…)

         25. Chronic (> 15 consecutive days) use of systemic steroids Safety aspects concerning
             female subjects of childbearing potential

         26. Breast-feeding

         27. Pregnancy

         28. Woman with positive pregnancy test

         29. Woman not willing or not able to use a highly effective contraceptive method during
             the 6-month active follow-up period. Highly effective birth control methods are:

               1. Combined (estrogen and progestogen containing) hormonal contraception associated
                  with inhibition of ovulation (oral, intravaginal, transdermal)

               2. Progestogen-only hormonal contraception associated with inhibition of ovulation
                  (oral, injectable, implantable)

               3. Intrauterine device

               4. Intrauterine hormone-releasing system

               5. Bilateral tubal occlusion Other exclusion criteria

         30. Body Mass Index (BMI) of 40 kg/m2 or greater at baseline

         31. Signs of an active drug or alcohol dependence, serious current illness, mental illness
             or any other factors which may interfere with subject's ability to understand and
             comply with study requirements, as judged by the Investigator

         32. Life expectancy less than 12 months at screenin
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.


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? Entailment