AP-008 Multiple Injection Study Evaluating Safety and Efficacy of Ampion in Osteoarthritis

A total of approximately 320 male or female subjects, aged from 40 to 85 years, with OA knee
pain, will be enrolled and randomized 1:1 across two study arms, to receive three (3) IA
injections of either the active drug (Ampion™ 4 mL) or a placebo injection at Baseline (Day
0) and Weeks 2 and 4 after confirming eligibility regarding the inclusion/exclusion criteria
listed below. Enrollment of Kellgren subjects will be limited to Kellgren III and IV only.

There will be seven (7) in-clinic visits and three (3) phone visits. Subjects will receive
three (3) IA injections of active drug (Ampion™ 4 mL) or placebo at Baseline (Day 0) and
Weeks 2 and 4. Subjects will also attend in-clinic visits at Week 6, Week 12, Week 20, Week
24 (final assessment). Post-treatment follow-up telephone calls will be made to each subject
within 24 hours of each IA injection (Baseline (Day 0) and Weeks 2 and 4) with each call
documented.

The clinical effects of treatment on OA knee pain will be evaluated during clinic visits at
Weeks 2, 4, 6, 12, 20, and 24 using the Western Ontario and McMaster Universities Arthritis
Index (WOMAC®) osteoarthritis Index 3.1 (pain subscore and function subscore) and an overall
global severity assessment (Subject's Global Assessment [PGA]).

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 (x-ray) acquired at screening and assessed
by a central reader. Subjects must have a Kellgren Lawrence Grade of III or IV for
inclusion in the study.

- 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) assessed at screening and
confirmed at randomization.

- Moderate to moderately-severe OA pain in the index knee (even if chronic doses of
non-steroidal anti-inflammatory drug [NSAID], which have not changed in the 4 weeks
prior to screening, have been/are being used).

- No analgesia taken 24 hours before efficacy measure.

Exclusion Criteria:

- As a result of medical review and screening investigation, the Principal Investigator
considers the subject unfit for the study.

- Previous Ampion™ injection in the index knee.

- Known clinically significant liver abnormality (e.g., cirrhosis, transplant, etc).

- 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 in the index knee.

- Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis
or joint replacement in the index knee, as assessed locally by the Principal
Investigator.

- Isolated patella femoral syndrome, also known as chondromalacia, in the index knee.

- 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
OA).

- Major injury to the index knee within the 12 months prior to screening.

- Severe hip OA 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 treatment or likely to be changed during the duration of
the study.

- Use of the following medications are exclusionary:

- IA injected pain medications in the study knee during the study;

- Analgesics containing opioids. NSAIDs may be continued at levels preceding the study
and acetaminophen is available as a rescue medication during the study from the
provided supply;

- Topical treatment on osteoarthritis index knee during the study;

- Significant anticoagulant therapy (e.g., Heparin or Lovenox) during the study
(treatment such as Aspirin and Plavix are allowed);

- Systemic treatments that may interfere with safety or efficacy assessments during the
study;

- Immunosuppressants;

- Use of corticosteroids > 10 mg prednisolone equivalent per day (if ≤ 10 mg
prednisolone, the dose must be stable).

- Any human albumin treatment in the 3 months before randomization.