Clinical trial: A Clinical Trial to Evaluate the Safety and Efficacy of Retreatment With Intra-articular LBSA0103 Injections in the Patients With Osteoarthritis of the Knee (NCT02122601)

Eligibility criteria:
Inclusion Criteria:

          1. A patient diagnosed with one or both knee osteoarthritis based on the clinical
             diagnosis criteria of the American College of Rheumatology (ACR) (there should be knee
             pain and in addition, at least three of the following six conditions have to be
             satisfied: 1. Over 50 years of age 2. Less than 30 minutes of morning stiffness 3.
             Crepitus on active motion 4 Bony tenderness 5. Bony enlargement 6. No palpable warmth
             of synovium)

          2. Adult male and female patients of age 40 or above diagnosed with knee osteoarthritis
             with the Kellgren & Lawrence Grade of I - III by x-ray within 6 months before the
             screening visit (based on -2 weeks) or by x-ray at the screening visit

          3. A patient who has at least one knee with a weight-bearing pain value of 40 mm or more
             when weight-bearing pain (100 mm-VAS) is measured

          4. A patient taking aspirin at a low dose (300 mg or less per day) who is willing to take
             aspirin constantly at the same dose until the clinical study is completed and can
             refrain from taking aspirin within 24 hours before each visit.

          5. A patient who can walk without depending on a walking aid such as walker, cane, etc.
             but if the patient has been using a walking aid on a daily basis from six months ago,
             the patient assessment can be conducted while including the walking aid and the
             walking aid must be used in the same way until the study is completed.

          6. A patient who can understand the meanings of an efficacy measurement questionnaire
             well and complete it

          7. A patient who heard an explanation about the purpose, method, effects, etc. of the
             clinical study and whose informed consent form has been signed by him/herself or
             subject's representative

          8. A patient who falls under one of the following four cases

               -  Patients who are surgically infertile

               -  Post-menopausal women who are above 45 years of age and 2 years after the last
                  menstruation

               -  Fertile premenopausal female patients or male patients without having a surgical
                  sterilization who have agreed to use at least two birth control methods
                  (including one of barrier methods) for at least 13 weeks after the administration
                  of the last investigational product to avoid pregnancy

                    -  Barrier methods: Condom, Diaphragm, Cervical cap(Pessary), Spermicide

                    -  Hormonal methods: Pills, Injection(Depot), Skin patch, Hormonal
                       implant(Implanon), Vaginal ring

                    -  Intrauterine Devices(IUDs): Cooper IUD(Loop), Hormonal IUD(Mirena)

                    -  Natural methods: Basic body temperature, Ovulation period, Coitus
                       interruptus, Abstinent

          9. A patient who discontinued analgesics, NSAIDs, condroichin sulfate/glucosamine and
             physical therapy or oriental medical treatment (acupuncture, cubbing therapy, moxa
             treatment) within 2 weeks before the administration (washout period) and has a will to
             discontinue them from the screening visit of the study to the end (however, 300 mg
             less per day of aspirin and acetaminophen, a rescue therapy, can be taken)

         10. A patient who didn't take any analgesic including aspirin and acetaminophen within 24
             hours before the administration

        Exclusion Criteria:

          1. Body mass index > 32

          2. A patient with rheumatoid arthritis, or other inflammatory or metabolic arthritis

          3. A patient with infection or severe inflammation at the joint like septic arthritis

          4. A patient with infection or skin disease at the site of administration

          5. A patient with secondary knee osteoarthritis caused by ochronosis, hemochromatosis,
             systemic disease, etc.

          6. A patient with a very painful musculoskeletal disease such as Sudek's atrophy, Paget's
             disease, or spinal disc herniation

          7. A poly-artricular patient with a severe osteoarthritis symptom at other site (e.g.,
             hip joint, etc.) which can have an effect on the assessment of the pain for knee joint

          8. Patients diagnosed with knee osteoarthritis with the Kellgren & Lawrence Grade of IV
             in X-ray within 6 months before the screening visit (based on -2 weeks) or X-ray at
             the screening visit

          9. A patient showing a clear loss in the joint space of patello-femoral joint (PFJ) in
             X-ray

         10. A patient who took following drug before the administration of investigational product
             (baseline visit):

               -  A patient who had HA at the target knee joint within the last 6 months

               -  A patient who was given an intra-articular knee joint injection with steroidal
                  agent within the last 3 months

               -  A patient who used steroidal agent systemically by oral administration within the
                  last 1 month (However, except for inhalant)

         11. A patient with moderate to severe joint effusion which was found to be positive
             through patella tap test, etc.

         12. A patient with alcoholism and alcoholic liver disease

         13. A patient with a serious heart disease or hepatic and renal dysfunction or a patient
             who showed the following laboratory test value:

               -  AST, ALT ≥ 3 times the upper limit of normal range

               -  Serum creatinine > 2mg/dl

         14. A patient who had a surgical procedure including arthroscopy on the target knee within
             the last 1 year (In case of a patient who had a history of joint surgery on other knee
             or hip joint, the patient shall be excluded if the assessment of the target knee is
             likely to be affected by that. )

         15. A patient who has a history of knee replacement surgery on the target knee joint

         16. A patient who does highly intensive aerobic exercise or heavy anaerobic exercise such
             as running or weight training which can have an effect on knee joint.

         17. A patient who needs to use an anticoagulant agent concurrently (However, except for
             aspirin of 300 mg or less per day)

         18. A patient who is mentally ill or can't understand the purpose and method of this
             clinical study

         19. A patient who shows hypersensitivity reaction to the investigational product of this
             clinical study

         20. A patient who is participating in other clinical study after having enrolled in this
             study, or participated in other clinical study within 1 month before the enrollment in
             this clinical study

         21. A patient who is considered to have a difficulty undergoing the clinical study at the
             discretion of the Principal Investigator

         22. A patient who was given one of the following drugs based on the day of administration:

               -  A patient who was given anesthetic within the last 48 hours

               -  A patient who took analgesics including acetaminophen and aspirin within the last
                  24 hour
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? 1