AP-003-B Study to Evaluate the Efficacy And Safety Of An Intra-Articular Injection Of Ampion™ In Adults With Pain With Osteoarthritis Of The Knee

A Randomized, Placebo-Controlled, Double-Blind Study To Evaluate The Efficacy And Safety Of
An Intra-Articular Injection Of AMPION™ In Adults With Pain Due to Osteoarthritis Of The
Knee

The primary trial objective is to evaluate the efficacy of 4 mL of AMPION™ versus 4 mL
placebo intra-articular (IA) injection in improving knee pain, when administered to subjects
suffering from OA of the knee.

The secondary trial objective is evaluation of the safety of an intra-articular injection of
AMPION™.

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 to 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