Safety and Efficacy of Investigational Anti-Influenza Immune Plasma in Treating Influenza

Morbidity and mortality occur despite treatment with current antivirals. Circulating
influenza H1N1 and H3N2 isolates are highly resistant to amantadine and rimantadine, whereas
previous seasonal H1N1 isolates were highly resistant to oseltamivir. So there is concern
that circulating influenza A/H1N1 2009 virus may also acquire oseltamivir resistance.

This randomized, open-label, multicenter phase 2 trial will assess the safety, efficacy, and
pharmacokinetics (PK) of anti-influenza plasma in subjects with influenza. Hospitalized
subjects with influenza at risk for severe disease (as defined in the inclusion criteria)
will be eligible for study participation. This study will enroll adults, children and
pregnant women.

Up to 40 sites in the United States will participate in this protocol. One hundred eligible
subjects will be randomized in a 1:1 ratio to receive either 2 units (or pediatric
equivalent) of anti-influenza immune plasma on Study Day 0 in addition to standard care or
standard care alone (50 subjects receiving standard care alone; 50 subjects receiving
anti-influenza immune plasma and standard care).

Subjects will be assessed on Study Day 0 (pre-dose), 30 minutes post-dose (plasma arm only),
and on Study Days 1, 2, 4, 7, 14, and 28. All subjects will undergo a series of efficacy,
safety, and PK (HAI) assessments during the study. Blood samples will be collected at each
time point (except Day 1). Nasal and oropharyngeal swabs for influenza PCR will be obtained
on Days 0,1,2,4 and 7.

Inclusion Criteria:

- Diagnosis of influenza A or B prior to enrollment

- Hospitalization for signs and symptoms of influenza (decision for hospitalization
will be up to the individual treating clinician).

- Abnormal respiratory status, defined as room air saturation of oxygen (SaO2) less
than 93% or tachypnea (respiratory rate above normal)

- Agree to the storage of specimens and data

- ABO compatible plasma available on site or available within 24 hours after
randomization with activity against locally circulating strains of influenza

Exclusion Criteria:

- Receipt of non-licensed treatment for influenza within the last 2 weeks (or plans to
receive any time during the study). This does not include licensed drugs at
nonapproved doses, off-label indications, or drugs available under an Emergency Use
Authorization (EUA).

- Symptoms or signs of the acute influenza-like illness have occurred for more than 7
days prior to enrollment.

- History of severe allergic reaction to blood products (as judged by the
investigator).

- Medical conditions for which receipt of 500 mL volume (or 8 mL/kg for pediatric
patients) may be dangerous to the subject (e.g. decompensated congestive heart
failure [CHF], etc.)

- Clinical suspicion that etiology of illness is primarily bacterial