Anti-Influenza Hyperimmune Intravenous Immunoglobulin Pilot Study (INSIGHT 005: Flu-IVIG Pilot)

The purpose of this randomized, double-blind, placebo-controlled trial of intravenous
hyperimmune immunoglobulin (Flu-IVIG) in individuals with influenza A or B is to determine
the pharmacokinetic (PK) profile of Flu-IVIG and assess whether antibody levels observed
following Flu-IVIG transfusion are similar to those predicted. This pilot study will inform
a larger study that will be powered to compare Flu-IVIG with placebo for efficacy. In
addition to informing the Flu-IVIG dosing required for the clinical outcomes trial, the
pilot study will compare influenza antibody levels and safety for study participants
randomly assigned Flu-IVIG and those assigned placebo, assess the feasibility of enrollment,
evaluate randomization and blinding procedures, and possibly obtain some preliminary data on
efficacy that may be used to inform sample size and study procedures for the clinical
outcomes study.

- INCLUSION CRITERIA:

1. Signed informed consent

2. Age greater than or equal to 18 years of age

3. Outpatients or inpatients who are PCR or rapid Ag positive for influenza A or B
preferably within 24 hours and no later than 6 days from symptom onset

4. Onset of illness no more than 6 days before randomization, defined as when the
patient first experienced at least one respiratory symptom, constitutional
symptom or fever

5. For women of child-bearing potential, a negative pregnancy test within one day
prior to randomization and a willingness to abstain from sexual intercourse or
use at least 1 form of hormonal or barrier contraception through Day 28 of the
study

6. Willingness to have blood and respiratory samples obtained and stored

EXCLUSION CRITERIA:

1. If hospitalized, admitted for reasons other than influenza or complications of
influenza

2. Women who are pregnant or breast-feeding

3. Strong clinical evidence (in the judgment of the site investigator) that the etiology
of illness is primarily bacterial in origin.

4. Prior treatment with any investigational drug therapy within 30 days prior to
screening

5. History of allergic reaction to blood or plasma products (as judged by the
investigator)

6. Known IgA deficiency

7. A pre-existing condition or use of medication that, in the opinion of the
investigator, may place the individual at a substantially increased risk of
thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or
clinically significant monoclonal gammopathy)

8. Serum creatinine greater than or equal to 1.5 x ULN or known active kidney disease
that may affect drug pharmacokinetics (e.g., nephrotic syndrome)

9. Presence of any pre-existing illness that, in the opinion of the investigator, would
place the individual at an unreasonably increased risk through participation in this
study

10. Patients who, in the judgment of the investigator, will be unlikely to comply with
the requirements of this protocol

11. Medical conditions for which receipt of 500mL volume may be dangerous to the patient
(e.g., decompensated congestive heart failure)

12. Suspicion that infection is due to an influenza strain or subtype other than
A(H1N1)pdm09, H3N2, or influenza B (e.g., H5N1, H7N9)