A Study to Evaluate the Efficacy & Safety of an Intra-Articular Ampion Injection for Pain of Osteoarthritis of the Knee

Inclusion Criteria: * Able to provide written informed consent to participate in the study; * Willing and able to comply with all study requirements and instructions of the site study staff; * Male or female, 40 years to 85 years old (inclusive); * Must be ambulatory; * Index knee must be symptomatic for greater than 6 months with a clinical diagnosis of OA and supported by radiological evidence (Kellgren Lawrence Grade II, III, or IV) read by a central reader; * WOMAC 5-point Likert pain subscale \<1.5 in the contralateral knee; * Moderate to moderately-severe OA pain in the index knee (rating of at least 1.5 on the WOMAC Index 3.1 5-point Likert Pain Subscale); * Moderate to moderately-severe OA pain in the index knee (even if chronic doses of nonsteroidal anti-inflammatory drug (NSAID), which have not changed in the 4 weeks prior to screening, have been/are being used); * Ability to discontinue NSAID use at Screening visit and/or 72 hours prior to the Baseline visit and for the duration of the clinical study (low dose Aspirin is allowed during the study); * No analgesia (including acetaminophen \[paracetamol\]) taken 24 hours prior to an efficacy measure; * No known clinically significant liver abnormality (e.g. cirrhosis, transplant, etc.). Exclusion Criteria: * As a result of medical review and screening investigation, the Principal Investigator considers the patient unfit for the study * A history of allergic reactions to human albumin (reaction to non-human albumin such as egg albumin is not an exclusion criterion) * A history of allergic reactions to excipients in 5% human albumin (N-acetyltryptophan, sodium caprylate) * Presence of tense effusions * Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis or joint replacement in the affected knee, as assessed locally by the Principal Investigator * Isolated patella femoral syndrome, also known as chondromalacia * Any other disease or condition interfering with the free use and evaluation of the index knee for the duration of the trial (e.g. cancer, congenital defects, spine osteoarthritis) * Major injury to the index knee within the 12 months prior to screening * Severe hip osteoarthritis ipsilateral to the index knee * Any pain that could interfere with the assessment of index knee pain (e.g. pain in any other part of the lower extremities, pain radiating to the knee) * Any pharmacological or non-pharmacological treatment targeting OA started or changed during the 4 weeks prior to randomization or likely to be changed during the duration of the study * Pregnancy or planning to become pregnant during the study. * Use of the following medications: * No IA injected pain medications in the study knee during the study * No analgesics containing opioids. * NSAIDs are not permitted during the study; acetaminophen is available as a rescue medication during the study from the provided supply. * No topical treatment on osteoarthritis index knee during the study * No significant anticoagulant therapy (e.g. Heparin or Lovenox) during the study (treatment such as low dose Aspirin and Plavix are allowed) * No systemic treatments that may interfere with safety or efficacy assessments during the study * No immunosuppressants * No use of corticosteroids * No human albumin treatment in the 3 months before randomization or throughout the duration of the study