Open Label Extension to Assess the Safety of Long-Term Treatment With Ampion for Severe Osteoarthritis (OA) of the Knee
Condition: Severe Osteoarthritis of the Knee
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: 4 mL injection of AMPION™
Intervention description: 4 mL injection of AMPION™
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Open Label
Masking: None (Open Label)
Enrollment: 94.0
Sex: All
Minimum age: 40 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Osteoarthritis; osteoarthritis of the knee

Summary:

      This Open Label Extension (OLE) study will assess the safety of long-term treatment with a 4
      mL intra-articular injection of Ampion™ in adults with pain due to severe osteoarthritis of
      the knee
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects who completed the AP-003-C Main study and have not developed any exclusionary
             criteria

          2. Able to provide written informed consent to participate in the study

          3. Willing and able to comply with all study requirements and instructions of the site
             study staff

          4. Male or female, 40 years to 85 years old (inclusive), as assessed in the AP-003-C Main
             Study

          5. Must be ambulatory, as assessed in the AP-003-C Main Study

          6. Study knee must have a clinical diagnosis of OA and supported by radiological evidence
             (Kellgren Lawrence Grade IV) as assessed in the AP-003-C Main Study.

          7. Moderate to moderately-severe OA pain in the study knee (rating of at least 1.5 on the
             WOMAC Index 3.1 5-point Likert Pain Subscale), as assessed in the AP-003-C Main Study

          8. Moderate to moderately-severe OA function in the study knee (rating of at least 1.5 on
             the WOMAC Index 3.1 5-point Likert Function Subscale), as assessed in the AP-003-C
             Main Study

          9. WOMAC A, 5-point Likert pain subscale <1.5 in the contralateral knee, as assessed in
             the AP-003-C Main Study

         10. Ability to discontinue NSAID ± 72 hours before/after injections (in-office visits).
             Low-dose Aspirin (81 mg) is allowed during the study but must not be taken at least 24
             hours prior to in-office visits.

         11. No analgesia (including acetaminophen [paracetamol]) taken 24 hours prior to an
             efficacy measure

        Exclusion Criteria:

          1. As a result of medical review and screening investigation, the Principal Investigator
             considers the patient unfit for the study

          2. Known clinically significant liver abnormality (e.g., cirrhosis, transplant, etc.)

          3. A history of allergic reactions to human albumin (reaction to non-human albumin such
             as egg albumin is not an exclusion criterion)

          4. A history of allergic reactions to excipients in 5% human albumin (N-acetyltryptophan,
             sodium caprylate)

          5. Presence of tense effusions

          6. Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis or
             joint replacement in the affected knee

          7. Isolated patella femoral syndrome, also known as chondromalacia

          8. 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)

          9. Major injury to the index knee within the last 12 months

         10. Severe hip osteoarthritis ipsilateral to the index knee

         11. Any pain that could interfere with the assessment of study knee pain (e.g. pain in any
             other part of the lower extremities, pain radiating to the knee)

         12. Any pharmacological or non-pharmacological treatment targeting OA started or changed 4
             weeks prior to entry into the OLE study, or likely to be changed during the duration
             of the OLE study

         13. Pregnancy or planning to become pregnant during the study

         14. Use of the following medications:

               1. No IA injected pain medications in the study knee during the study. No Hyaluronic
                  Acid (HA) or steroid injections in the study knee at least 12 weeks prior to Day
                  84 of the Extension Study. HA and steroid injections in the contralateral knee
                  (non-study knee) are acceptable while on study except ± 14 days of an Ampion
                  injection in the study knee.

               2. No analgesics containing opioids

               3. NSAIDs are not permitted ± 72 hours before/after injections at in-office visits;
                  acetaminophen is available as a rescue medication during the study from the
                  provided supply

               4. No topical treatment on the study knee during the study

               5. No significant anticoagulant therapy (e.g. Heparin or Lovenox) during the study
                  (treatment such as Aspirin and Plavix are allowed)

               6. No systemic treatments that may interfere with safety or efficacy assessments
                  during the study

               7. No immunosuppressants

               8. No use of corticosteroids

               9. No human albumin treatment in the 3 months prior to the AP-003-C Main Study or
                  interim period prior to enrollment into the OLE study. No human albumin treatment
                  throughout the duration of the OLE study