Study of Ampion for the Treatment of Pain and Function in Patients With Severe Osteoarthritis of the Knee.

A Randomized, Controlled, Double-Blind Study to Evaluate the Efficacy and Safety of an Intra-Articular Injection of Ampion in Adults With Pain Due to Severe Osteoarthritis of the Knee.

The purpose of this study is to confirm the safety and efficacy of Ampion for the treatment of pain and function in patients with severe osteoarthritis of the knee.

This study is a randomized, double-blind, single dose design.

The co-primary trial objectives are to evaluate the greater efficacy for pain improvement and function improvement of 4 mL Ampion versus saline intra-articular (IA) injection when applied to patients suffering from severe osteoarthritis of the knee (OAK). Efficacy will primarily be assessed with WOMAC A pain and WOMAC C function scores.

Mean change in the WOMAC A weekly pain scores from Baseline to Week 12 will be compared between Ampion and saline control. Mean change in WOMAC C function score will be compared between Ampion and saline control. This will test whether Ampion is superior to saline in improving pain and function.

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
• Must be ambulatory
• Index knee must be symptomatic for greater than 6 months with a clinical diagnosis of OAK and supported by radiological evidence (Kellgren-Lawrence Grade 4) that is not older than 6 months prior to the date of screening
• Moderate to moderately-severe osteoarthritis (OA) pain in the index knee (rating of at least 1.5 on the WOMAC Index 3.1 as measured by 5-point Likert Pain Subscale) assessed at screening
• Ability to temporarily discontinue nonsteroidal anti-inflammatory drug (NSAID) for 48 hours prior to scheduled clinical efficacy evaluations
• No analgesia (including acetaminophen [paracetamol]) taken 12 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

• Use of the following medications:

  1. No IA injected pain medications in the study knee during the study
  2. No analgesics containing opioids. NSAIDs may be continued at levels preceding the study, however may not be used 48 hours prior to efficacy evaluations, and acetaminophen is available as a rescue medication during the study from the provided supply
  3. No topical treatment on osteoarthritis index knee during the study
  4. No significant anticoagulant therapy (e.g. Heparin or Lovenox) during the study (treatment such as Aspirin and Plavix are allowed)
  5. No systemic treatments that may interfere with safety or efficacy assessments during the study
  6. No immunosuppressants
  7. No use of corticosteroids > 10 mg prednisolone equivalent per day
  8. If corticosteroid use is ≤ 10 mg prednisolone equivalent per day, and if clinically indicated, subjects should be allowed to decrease their corticosteroid use. Additionally, some subjects may need to increase their steroid dose to treat worsened symptoms in the treated knee, and subjects who increase their corticosteroid dose above their starting dose of corticosteroid during the study will be treated as "treatment failures" for efficacy analysis

• No human albumin treatment in the 3 months before randomization or throughout the duration of the study