Key Inclusion and Exclusion Criteria
- Key Inclusion Criteria
- >40 years of age
- Diagnosis of OA of the index knee according to ACR criteria, including radiological evidence of OA (Kellgren-Lawrence grades 2 or 3).
- Continual pain for at least 6 months prior to the Screening Visit. This includes pain that has persisted despite conventional treatment, defined as any one of the following medications taken daily during any one of the preceding 6 months:
- acetaminophen (2- 4 grams per day)
- maximum tolerated and recommended dose of an NSAID
- acetaminophen/codeine combination (i.e. Tylenol No. 2, 3, 4) taken at least 3 times daily.
- Daily knee pain for the 4 weeks preceding the Screening Visit.
- Pain score of ≥ 4 (0-10 NRS) in the index (more symptomatic) knee at Screening and Baseline.
- If the Subject is taking analgesics/NSAIDs , the analgesic/NSAID dosage has been stable for 14 days prior to the Baseline visit.
- Key Exclusion Criteria
- Has other bone and articular diseases (antecedents and/or current signs).
- Has a BMI greater than 40.
- Planned/anticipated surgery of the index knee during the study period.
- Subject already scheduled for any surgery during the time of the study or within 70 days after the end of treatment.
- Prior arthroscopic or open surgery of the index knee within 12 months of Baseline.
- History of cancer or lymphoproliferative disease other than:
- Successfully and completely treated cervical dysplasia, with no recurrence within the last five years.
- Basal or Squamous Cell Carcinoma that has been adequately treated or excised.
- History of: neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease, uncontrolled diabetes, unstable ischemic heart disease, active congestive heart failure, New York Heart Association (NHYA) III, IV, inflammatory bowel disease, active peptic ulcer disease, recent stroke (within 12 weeks of Screening), or any other condition, which in the opinion of the investigator, would put the patient at risk by participating in the study.
- Concurrent local or systemic infection, persistent or severe infection(s) requiring hospitalization or treatment with IV antibiotics within 30 days, or oral antibiotics within 14 days, prior to Baseline.
- History of active tuberculosis or listeriosis, or other infections suggestive of significant or profound immunosuppression, such as Pneumocystis carinii, aspergillosis or other systemic protozoal or fungal infections.
- Has latent TB or has other risk factors for the activation of latent TB
- Positive serology for Hepatitis B or Hepatitis C that indicates active infection, or history of positive HIV status.
- Currently taking or likely to begin anti-retroviral therapy at any time during the course of the study.
- Has received intra-articular injections of steroid and/or hyaluronate compounds into the index knee within 12 weeks prior to Baseline; however, allowed in the non-index knee.
- Glucosamine and/or chondroitin to be withdrawn on all patients at screening. Can’t be introduced during the trial.
- If treatment for osteoarthritis (NSAID) or osteoporosis (bisphosphonates, selective estrogen receptor modulators) is necessary, it will have to be continued, unmodified if at all possible for the entire duration of the study. If the subject does not wish to continue them during the study, they must be stopped 14 days prior to the Baseline visit.
- Subjects who have used compounds containing non-approved agents for arthritis or agents claiming to possess disease/structure-modifying properties in the 14 days prior to the Baseline visit (see exception above).
- Subjects who are taking lithium carbonate, phenytoin or anticoagulants (with the exception of aspirin up to a maximum daily dose of 325 mg), or calcitonin.
- Subjects who use immunosuppressive drugs, e.g., methotrexate or hyrdroxychloroquine must withdraw treatment 1 month prior to baseline, to be eligible to enter the study.
- Topical analgesics and NSAID’s should be excluded from being used on the target knee as of the screening visit.
Kellgren-Lawrence Grading of OA with Examples
- Kellgren-Lawrence Grading with examplesEvaluation of KL grading must be performed on a weight-bearing frontal radiograph. The images below are examples of the grade shown immediately above the image. Both knees (left and right) are the same grade in each image.
Grade 0: no radiographic features of OA are present
Grade 1: doubtful joint space narrowing (JSN) and possible osteophytic lipping
Grade 2: definite osteophytes and possible JSN
Grade 3: multiple osteophytes, definite JSN, sclerosis, possible bony deformity
Grade 4: large osteophytes, marked JSN, severe sclerosis and definite bony deformity