Clinical trial: Study of Cingal™ for the Relief of Knee Osteoarthritis Compared to Triamcinolone Hexacetonide (NCT03191903)

Eligibility criteria:
Inclusion Criteria:

          -  Screening Inclusion Criteria

               1. Subject is 40-75 years old, with a Body Mass Index (BMI) ≤ 40 kg/m2.

               2. Subject has Kellgren-Lawrence (K-L) severity grade I, II or III in the index knee
                  as determined by X-ray. Contralateral knee: K-L severity grade 0, I or II.

               3. Subject has had at least two signs and at least two symptoms of OA disease (based
                  on the European League Against Rheumatism (EULAR) recommendations for diagnosing
                  knee OA) in the index knee for at least 6 months despite conservative treatment
                  (weight reduction, physical therapy, pain medications, etc.). The EULAR signs and
                  symptoms are as follows:

                    -  Signs: crepitus, restricted movement and bony enlargement

                    -  Symptoms: persistent knee pain, limited morning stiffness and reduced
                       function

               4. Subject must be willing to abstain from other IA treatments of the knee for the
                  duration of the study.

               5. Subject is willing to discontinue all analgesics including NSAIDs, except
                  acetaminophen/paracetamol, at least seven days before the treatment injection and
                  through the completion of the study.

               6. Subject is willing to use only acetaminophen/paracetamol (up to a maximum of 4.0
                  grams per day per the package insert) for the treatment of joint pain for the
                  duration of the study. At least forty eight hours prior to the Baseline Visit and
                  each follow-up visit, the subject is willing to discontinue use of
                  acetaminophen/paracetamol.

               7. Subject is willing to maintain a stable dose of oral glucosamine and/or
                  chondroitin sulfate products throughout the study, if taken prior to signing the
                  informed consent form (ICF).

               8. Subject is able to understand and comply with the requirements of the study and
                  voluntarily provides consent.

        Exclusion Criteria:

          -  1. Subject received an IA injection of Hyaluronic Acid (HA) and/or steroid in either
             knee within 6 months of signing the informed consent form (ICF). A subject will be
             excluded if they are planning to receive an HA or steroid injection (other than the
             study injection) in either knee during the course of this study.

             2. Subject had an arthroscopy of either knee within 3 months of signing the ICF.

             3. Subject had an open surgical procedure of either knee or hip or any surgery of the
             spine within 12 months of signing ICF. Subject plans to have knee, hip or spine
             surgery within the study period.

             4. Subject has intra-articular trauma to the index knee. Subject has concurrent
             multi-system or multi-limb trauma.

             5. Subject has evidence or medical history of the following diseases in the index
             knee: septic arthritis; inflammatory joint disease; history of Reiter's syndrome;
             gout; chondrocalcinosis associated with recurrent episodes of acute synovitis of the
             knee consistent with pseudogout; osteochondritis dissecans, Paget disease of the bone;
             ochronosis; acromegaly; hemochromatosis; primary osteochondromatosis; known history of
             Wilson disease; heritable disorders or collagen gene mutations.

             6. Subject has a history of cartilage repair surgery in the index knee within 3 years
             of signing the ICF.

             7. Subject has a history of ACL repair, reconstruction or injury in the index knee
             within 3 years of signing the ICF.

             8. Subject has X-ray findings of acute fractures, severe bone loss, avascular
             necrosis, severe bone or joint deformity in the index knee.

             9. Subject has significant varus or valgus deformity greater than 10 degrees in either
             knee.

             10. Subject has a clinically apparent tense effusion of the index knee. 11. Subject
             has knee instability in either knee per the Investigator's assessment.

             12. Subject requires consistent use of an assistive device (e.g. wheelchair, walker,
             etc.) Occasional use of a cane is acceptable.

             13. Subject has medical condition(s) which could affect study assessments or may
             adversely affect the safety and/or success of the study treatment. This includes but
             is not limited to the following: a. Peripheral neuropathy severe enough to interfere
             with evaluation of the subject, b. Vascular insufficiency severe enough to interfere
             with evaluation of the subject, c. Active fibromyalgia, d. Hemiparesis involving
             either lower extremity, e. Immunocompromised or immunosuppressive disorder or
             receiving medications to treat immunosuppressive disorders, f. Systemic bleeding
             disorder(s), g. Current malignancy or treatment within the last 5 years, except for
             non-melanoma skin cancer, h. Significant psychiatric disorder, i. Active drug and/or
             alcohol abuse within the past year, j. Uncontrolled diabetes with a screening HbA1c of
             >7%.

             14. Subject is taking medications at the time the subjects signs the ICF which could
             interfere with the treatment procedure, healing and/or assessments. This includes but
             is not limited to oral or injectable anticoagulant treatments, anti-aggregant platelet
             treatment, chronic opioid analgesics. Low dose aspirin used for cardiovascular
             protection is allowed if a stable regimen is maintained for the duration of the study.

             15. Subject is receiving treatment using electromagnetic stimulation and/or low
             intensity ultrasound in the index knee at the time of signing the ICF, within 3 months
             of signing the ICF or plans to receive treatment any time during the study period.

             16. Subjects who had an oral, intramuscular, intravenous, rectal suppository or
             topical (excluded in index knee only) corticosteroid within 30 days of signing the ICF
             are excluded. Topical corticosteroid use at any site other than the index knee is
             allowed.

             17. Subject has a pre-treatment contraindication to IA injections or aspiration of the
             index knee, including cutaneous infection in the injection site area, active IA
             infection (as suggested by moderate or marked effusion), knee deformity or condition
             which, in the opinion of the Investigator could jeopardize the sterility or delivery
             of the IA injection.

             18. Subjects with a history of hypersensitivity to any of the ingredients in the
             hyaluronan or previous hypersensitivity to the administration of corticosteroids or an
             inability to tolerate acetaminophen/paracetamol.

             19. Subject has any contraindication to the receipt of a corticosteroid. 20. Subject
             is receiving or in litigation for worker's compensation. 21. Subject is a woman who is
             pregnant or breastfeeding at the Screening Visit or a woman of child bearing potential
             who refuses to use effective contraception during the course of the study.

             22. Subject was involved in any other research study involving an investigational
             product, or a new application of an approved product, within 60 days of signing the
             ICF.

        Baseline Inclusion Criteria

        1. Subject has a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
        pain-sub-score ≥ 40 mm and ≤ 90 mm in the affected knee and ≤ 30 mm in the contralateral
        knee on a 100 mm Visual Analog Scale (VAS) scale.

        Baseline Exclusion Criteria

          1. Subject has a decrease of ≥ 20 mm in the WOMAC pain-sub-score (average of 5 pain
             scales) from Screening to Baseline in the index knee on a 100 mm Visual Analog Scale
             (VAS) scale.

          2. Subject has a synovial fluid aspirate volume > 20 mL in the index knee.

          3. Subject has a contraindication to continue with the study treatment injection based on
             the visual appearance of the synovial fluid aspirate unless the fluid is examined
             microscopically prior to injection with no clinically significant findings (e.g.
             bacteria, crystals or blood).

          4. Subject has range of motion of less than 100° flexion in either knee.
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 75 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