This is a prospective, Phase III, randomized, double-blind (third party administration with blinded-evaluators)
Approximately 332 subjects will be randomized in this study at multiple investigator sites. A period of approximately 18 months is anticipated from the time the first subject is enrolled to the completion of the last subject visit (last subject out). Individual subject participation will last approximately 6 months.
BACKGROUND & RATIONALE
Hyaluronan (HA), is a naturally occurring linear polysaccharide composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine. HA is synthesized by the chondrocytes in the cartilage and by the type B synoviocytes in the synovial lining. The HA synthesized by the former becomes integrated in the cartilage matrix whereas the latter is released into the joint cavity, where it plays a functional role (lubricating and cushioning properties during joint movement).
Osteoarthritis (OA) of the knee is a common degenerative arthropathy and a leading cause of disability in older adults. Although OA is quite heterogeneous in its clinical aspects, typical clinical features include chronic pain, inflammation, stiffness, and limitation of motion, bone deformity, and ultimately overall functional impairment of the involved joint when the disease is progressive. The disease is characterized by a reduction in the lubricating and viscoelastic properties of the synovial fluid, due to a reduction of the concentration and molecular weight of HA, accompanied by progressive destruction of the cartilage surface.
Clinical studies have demonstrated that weekly Hyalgan injections once a week for 3 to 5 weeks significantly improve pain and functional status in subjects with knee OA. The effect is delayed but progressive over time: the maximum benefit is reached 21 to 28 days after the first injection. After treatment has been completed, the effect lasts up to 6 months and up to 1 year in some subjects. Since this new hydrogel has higher viscosity and elasticity in solution than Hyalgan, similar effects on knee OA are expected with a regimen of a reduced number of injections.
To evaluate the effectiveness of two 3 mL IA injections of this new hydrogel in comparison with two 3 mL IA injections of a placebo in providing superior pain relief for the treatment of subjects with symptomatic primary OA of the knee as measured by the WOMAC Pain Subscale.
Subjects must meet all of the following inclusion criteria to be eligible:
Male or female ambulatory out-patients at least 40 years of age. Note: subjects using canes as an assistive device are allowed if these were used for at least 1 month prior to Screening and there are no plans for change throughout the study. Subjects undergoing physical therapy are allowed if started at least 1 month prior to Screening and there are no plans for change throughout the study
Medical history of OA symptoms of the knee for at least 6 months prior to the Screening visit
Meet American College of Rheumatology clinical and radiographic criteria for OA (http://www.achieveclinical.com/
Suffering from primary knee pain. Note: subjects with bilateral OA of the knee will be allowed as long as they can differentiate pain in the target knee, do not need to use analgesics for treatment of their contralateral knee, and do not expect to receive treatment of the contralateral knee during the study
Kellgren-Lawrence Grade 2 to 3 severity OA of the knee with presence of osteophytes determined from X-rays of the knee obtained within 3 months of Baseline visit; i.e. in the tibio-femoral compartment of the target knee with at least 1 osteophyte and measurable joint space, as diagnosed by standard X-rays (anteriorposterior view [weight bearing extension or semi-flexion]
Comply with at least 1 of the following additional criteria: age above 50 years, crepitus, or morning stiffness persisting less than 30 minutes
Have discontinued use of all systemic analgesic/nonsteroidal anti-inflammatory drug (NSAID) therapy prior to Baseline and agree not to resume them during study. Note: acetaminophen will be provided to subjects as rescue medication.
Able to read and understand the language and content of the study material, understand the requirements for follow-up visits, willing to provide information at the scheduled evaluations, and willing and able to comply with study requirements
Has undergone the informed consent process and has signed an approved consent form
Ability to report pain accurately, as determined by an R2 Fit to the Power Function Average score of at least 0.6 on the Focused Analgesia Selection Test (FAST)
If female of child-bearing potential, must have a negative urine pregnancy test and use a reliable form of contraception for at least 1 month prior to Screening and throughout the study. Note: to be considered females of non-child-bearing potential, females must be surgically sterile or postmenopausal as documented in medical history for at least 1 year
Minimum pain intensity of 15 on the WOMAC pain subscale (range from 0-50)
*Achieve Clinical Research conducts Phase II-IV Clinical Research Studies in Alabama (http://www.achieveclinical.com/