An Exploratory Clinical Study to Investigate Biomarkers of Senescence in Patients With Osteoarthritis of the Knee

This is an exploratory non-drug, interventional, hypothesis generating biomarker study. No
Investigational Product will be administered in the study, however, there are study related
procedures which are interventional such as arthroscopy, arthrocentesis and infusion of a
gadolinium-containing contrast agent.

Consented patients who meet the selection criteria undergo MRI imaging with and without
gadolinium contrast of both knees. Approximately seven days following the MRI imaging,
patients undergo an arthrocentesis of both knees to obtain synovial fluid and then an
arthroscopy of the target knee to obtain synovial and non-weight bearing cartilage tissues.

The patient will return to the clinic approximately seven days following the arthroscopy and
arthrocentesis procedures for a routine safety follow-up.

Inclusion Criteria:

1. Patients must be diagnosed as having primary (idiopathic) femoro-tibial
osteoarthritis (OA) of the knee as defined by a modified version of the American
College of Rheumatology Criteria (modified clinical and laboratory criteria) for at
least 6 months.

2. Kellgren-Lawrence (KL) score of grade 1 to 4 inclusive based on a standardized,
semi-fixed, weight-bearing radiograph of the knee.

3. Adults of age ≥ 35 years

4. Body Mass Index less than or equal to an upper limit of 35 kg/m2

5. Patients who are able to commit the time required to attend all study visits

6. Normal clinical laboratory results with no clinically significant organ dysfunction
which, in the opinion of the investigator, would preclude patient from entering the
study

Exclusion Criteria:

1. Any condition, including laboratory findings and findings in the medical history or
in the pre-study assessments, that, in the opinion of the Investigator constitutes a
risk or contraindication for participation in the study or that could interfere with
the study objectives, conduct or evaluation

2. Prior open knee surgery to the target knee including but not limited to Anterior
Cruciate Ligament Repair

3. Patients who have had prior arthroscopy and intraarticular treatments for the
management of osteoarthritis such as administration of hyaluronic acid or
corticosteroids within the last 6 months

4. Patients with traumatic knee injury who are scheduled for arthroscopic repair
procedures to either target or non-target knee

5. Patients who are deemed to be at risk of acute renal insufficiency of any severity
due to hepato-renal syndrome or who are in the peri-operative liver transplant
period.

6. Patients with Diabetes Mellitus.

7. Patients with renal dysfunction as defined by a Glomerular Filtration Rate <60
ml/min/1.73m2 by laboratory testing.

8. Known allergic or hypersensitivity reaction to gadolinium-based contrast agents or
patients who have other contraindications for MRI

9. Patients requiring anticoagulation therapy other than low dose (81 mg or less)
aspirin

10. Treatment with an unapproved investigational therapeutic agent and/or experimental
therapeutic procedure on the target knee within 24 weeks prior to screening

11. Any active known or suspected systemic autoimmune disease Permitted on Study

- vitiligo

- residual hypothyroidism due to autoimmune condition only requiring hormone
replacement

- psoriasis not requiring systemic treatment for 2 years

- conditions not expected to recur in the absence of an external trigger Excluded
on Study

- documented history of inflammatory bowel disease (including ulcerative colitis
and Crohn's disease)

- symptomatic autoimmune conditions (e.g., rheumatoid arthritis, systemic
progressive sclerosis [scleroderma])

- systemic lupus erythematosus

- autoimmune vasculitis (e.g. Wegener's Granulomatosis)

- patients with motor neuropathy considered of autoimmune origin (e.g.
Guillain-Barré Syndrome)

12. History of previous surgery (Total or Partial Knee Replacement) on the Target knee

13. Lesions at the planned site of arthroscopy which would present a contraindication to
the procedure such as open wounds or infection of the skin

14. Any known active infection, including suspicion of intra-articular infection and/or
infections that may compromise the immune system such as HIV, Hepatitis B or
Hepatitis C infection

15. History of sarcoma and/or history of other active malignancy within the last 5 years,
except basal cell carcinoma, carcinoma in situ of the cervix and squamous cell
carcinoma of the skin

16. Secondary osteoarthritis, including:

- Joint dysplasias

- Crystal-induced arthropathy (gout, calcium pyrophosphate deposition disease)

- Aseptic osteonecrosis

- Acromegaly

- Paget's disease

- Ehlers-Danlos Syndrome

- Gaucher's disease

- Stickler's syndrome

- Joint infection

- Hemophilia

- Hemochromatosis

- Neuropathic arthropathy of any cause

17. Patients with risk factors for OA of the knee (e.g.: obesity, meniscectomy) are not
considered as having secondary OA and can be included in this study

18. Female patients who are pregnant. Female patients who are breast-feeding are eligible
for enrollment providing the patient agrees not to breast-feed for 24 hours after
receiving gadolinium for GE-MRI. Female patients of child-bearing potential must
agree to utilize adequate contraceptive measures during the course of the study.

19. Patients who do not have the legal capacity or medical competency to provide consent;
consent via legally authorized representative is not accepted.