Patient case (clinical description): 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's own account: 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.

Clinical trial: 2 Weekly Intra-articular Hyaluronan Knee Injections, Given 1 wk. Apart, of HYMOVIS Combined With Physical Exercise Program (PEP) Compared to PEP Alone, in Relatively Young, Active Population of Subjects With Patellofemoral Osteoarthritis (PFOA) and/or Tibiofemoral Osteoarthritis (TFOA)

Eligibility criteria:
Inclusion Criteria:

          -  Male or female ≥21 years and ≤60 years old and with BMI ≤40

          -  Moderate to severe knee OA pain ≥3 and ≤8 on the NRS pain subscale in the affected
             knee (signal knee)

          -  Mild or no pain ≤3 on the numeric rating scale (NRS) pain subscale in the
             contralateral knee (unaffected knee)

          -  Persistent knee pain lasting at least 3 months prior to Screening

          -  Active life-style (play or train themselves at least 2 to 3 times per week)

          -  Diagnosis of knee OA confirmed by radiographic assessment (must be performed within 6
             months prior to screening visit):

               1. anterior-posterior view (weight bearing extension or semi-flexion) of
                  tibiofemoral joint, (posterior-anterior/Rosenberg view as an additional
                  alternate)

               2. lateral view of both the tibiofemoral and patellofemoral joints

               3. Merchant X-ray (or Sunrise) view for patellofemoral joint.

          -  Radiographic assessment must confirm K-L Grade 1 to 3 for TFOA and/or K-L Grade 1 to
             for PFOA.

          -  Radiographic assessment confirms normal articulation of patella and trochlea in
             Merchant (or Sunrise) view

        Exclusion Criteria:

          -  Radiographic assessment confirms abnormal patellofemoral tracking or articulation in
             lateral and/or Merchant view (or Sunrise View)

          -  Major injury to or disorder of the contralateral knee or other weight-bearing joint
             that would interfere with the study assessments.

          -  Secondary OA of the study joint due to a prior or concomitant condition (e.g., septic
             arthritis, inflammatory joint disease, gout, articular fracture, major dysplasia, or
             congenital abnormality, hemochromatosis, etc.).

          -  Surgery to the study joint within the previous 12 months prior to Screening. Surgery
             to the contralateral knee or other weight-bearing joint within the previous 12 months
             that would interfere with the study assessments.

          -  Patients with either total joint replacement implants, unicondylar implants or
             patellofemoral replacement implants in the affected joint.

          -  Ligament reconstruction of the affected knee within 3 years.

          -  Inflammatory arthropathies such as rheumatoid arthritis, lupus, or psoriatic
             arthritis.

          -  Episode of gout or calcium pyrophosphate (pseudogout) diseases within 6 months prior
             to Screening.

          -  IA or local peri-articular corticosteroid injections to the study joint/knee within 8
             weeks (2 months) prior to Screening or to any other joint (other than the study joint)
             or soft tissue area within 1 month prior to Screening.

          -  Any oral corticosteroid within 1 month prior to Screening. Steroid inhalants are
             permitted if the Subject has been on a stable regimen for the past 1 month prior to
             Screening and remains on this regimen throughout the course of the trial.

          -  Intra-articular HA in the study joint within 6 months prior to Screening.

          -  History of allergic reaction to an intra-articular Hyaluronic acid injection.

          -  Known hypersensitivity (allergy) to gram positive bacterial proteins.

          -  Use of glucosamine or chondroitin sulfate containing products unless the subject is on
             stable doses for at least 14 days prior to Screening and willing to remain on these
             stable doses throughout the course of the study.

          -  Inability to perform the climbing stair test.

          -  X-ray findings of acute fractures, severe loss of bone density, avascular necrosis
             and/or severe deformity.

          -  Axial deviation of the lower limbs greater than 20 degrees in valgus or varus on
             standing X-ray.

          -  Symptomatic OA of either hip or spine with a pain score ≥2 on the NRS on or off pain
             medication.

          -  Clinically significant medio-lateral and/or anterior-posterior instability.

          -  Osteonecrosis of either knee.

          -  Participation in a physical therapy regimen that has not been stable during the 1
             month prior to Screening and the subject is unwilling or unable to maintain the same
             regimen throughout the course of the trial or is unwilling to stop previously
             prescribed or self-initiated physical therapy regimen and switch solely to and
             initiate study defined PEP program.

          -  K-L Grade 4 TFOA of the knee (i.e., large osteophytes, marked narrowing, severe
             sclerosis, and definite deformity).

          -  K-L Grade 4 PFOA of the knee (i.e., large osteophytes, marked narrowing, severe
             sclerosis, definite deformity)

          -  Hemiparesis of the lower limbs.

          -  Significant surgery of lower limbs (hip, ankle, foot) that may interfere with knee
             assessments.

          -  Chronic use of analgesia for pain (including pain in the other knee or any other
             joint) that may interfere with the evaluations of the test knee (such as possible use
             of rescue medication for these other conditions).

          -  Known allergies to acetaminophen and hyaluronan preparations.

          -  Know hypersensitivity (allergy) to anesthetics

          -  Recurrent medical history of severe allergic or immune-mediated reactions.

          -  Active infection or skin diseases in the area of the potential injection site or
             joint.

          -  Any dermatological disease overlying the signal joint that would contraindicate
             multiple injections or aspirations.

          -  Use of any agent reported to have symptom relief for arthritis or be a
             disease/structure modifying drug (e.g. doxycycline, long-term tetracycline,
             s-adenosylmethionine [SAM], methylsulfonylmethane [MSM] or dimethylsulfoxide [DMSO],
             dietary supplements or any herbal remedy taken for arthritic and joint conditions
             within the past month (exceptions as specified in Exclusion #14).

          -  Peripheral neuropathy that would be severe enough to interfere with the evaluation of
             the subject.

          -  Psychological status (e.g., anxiety, depression, poor sleep quality, pain
             catastrophizing, etc.) that may interfere with functional assessment of the target
             knee.

          -  Vascular insufficiency of lower limbs that is severe enough to interfere with the
             evaluation of the subject.

          -  Concomitant therapy with anticoagulants (low dose aspirin, not exceeding 325 mg per
             day as an anti-thrombotic agent is permitted if stable for 1 month prior to Screening
             and remains stable throughout the study).

          -  Any concomitant disease(s) or condition(s) that may interfere with the free use and
             evaluation of the affected knee for the 6 months course of the trial (cancer, other
             rheumatic diseases, gout, severe congenital defects, etc.).

          -  Any serious mobility problems (e.g. Parkinson's disease) or claustrophobia

          -  Any concomitant chronic disease(s) or condition(s) that may predispose them to a high
             probability of interfering with the completion of the 6-month follow-up of the study
             such as peptic ulcer, liver disease, severe coronary disease, renal disease, cancer,
             pregnancy, alcoholism, drug abuse, mental state, or other clinically significant
             condition.

          -  Excessive alcohol consumption or alcoholism that would be contraindicated with the use
             of acetaminophen.

          -  Use of marijuana, whether prescribed or not

          -  Any clinically significant diagnostic test and/or abnormal laboratory test result(s)
             that, in the opinion of the clinical investigator, may place the subject's health at
             risk, impact the study, or impact the subject's ability to complete the study.

          -  Inability to legally comprehend the details and nature of the study for any reason,
             including psychiatric illness.

          -  Likelihood of protocol violations or unlikely to compete the study for any reason, as
             determined by the clinical investigator.

          -  Continued participation in an experimental drug/device study or any clinical trial
             within the previous 8 weeks prior to Screening. Subjects must have fully completed
             participation in an experimental drug/device study of any clinical trial at least 8
             weeks prior to screening.

          -  Pregnancy, breastfeeding, planned conception, premenopausal women who have not had
             tubal ligation, hysterectomy, or are unwilling or unable to utilize contraceptive
             measures (or contraception)

          -  Prior history of any malignancy with the exception of basal cell carcinoma of the skin
             treated more than 2 years prior to Screening.

          -  Significant bleeding diathesis.

          -  Participation in current litigation for injuries related to the study knee or other
             injuries that might interfere with their completion of the study protocol.

          -  Non-English speaking subjects.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 21 Years old.
Subject must be at most 60 Years

Eligibility (NLI label): Contradiction