A Pilot Study for Collection of Anti-Influenza A Immune Plasma

Two types of influenza A widely circulate in humans and cause seasonal outbreaks and
epidemics - H1N1 (swine flu) and H3N2 (a subtype abundant in seasonal influenza). During the
2009-2010 influenza season, the most commonly reported virus was influenza A (H1N1). However,
during the 2010-2011 influenza season, the most commonly reported virus was influenza A
(H3N2), but influenza A (H1N1) viruses and influenza B viruses circulated as well.

A certain age group may be hit harder by one type of influenza virus than another (for
example, the 2009 H1N1 virus disproportionately affected people younger than 65 years of age
rather than those older than 65, whereas H3N2 virus often affects those older than 65 years).
However, influenza A has a substantial health effect on every age group.

Due to the limited therapeutic options for influenza and significant morbidity and mortality
despite treatment, additional therapeutics are warranted. One potential therapeutic that is
fairly rapidly available is the use of anti-influenza A immune plasma as immunotherapy.

The objective of this protocol is collection of anti-influenza A immune plasma from male
volunteers that meet criteria for use in human plasma therapy studies. The use of plasma from
male donors will minimize the risk of transfusion related acute lung injury (TRALI), which
has been associated with antibodies (likely generated during pregnancy) found in female
plasma. For this reason, only male donors will be enrolled.

This protocol does not administer any investigational product, but rather collects plasma
from subjects with a high anti-influenza A antibody titer (convalescent survivors of
influenza infection or recipients of a licensed influenza vaccine).

Following screening of potential subjects to identify those who are not eligible to
participate in plasma donations and to determine the likelihood of having antibodies to
influenza A (H1N1 or H3N2) from a recent infection or immunization, enrolled subjects will
receive a baseline physical and laboratory examination. Eligible subjects with high influenza
A hemagglutination inhibition (HAI) titers will then be scheduled for at least 3 (and up to
20) plasma collection sessions. Following testing of the collected plasma for potential
pathogens, it may be used as therapeutic plasma, and/or it may be used for the manufacturing
of high titer anti-influenza A intravenous immune globulin (IVIG). Both options would support
clinical trials aimed at developing additional therapeutics for influenza infection.

- INCLUSION CRITERIA:

1. Provide written informed consent before initiation of any study procedures.

2. Male adults between the ages of 18 and 60 years old

3. History suggestive of having anti-influenza A antibodies (either of the
following):

1. An influenza like illness (e.g. fever, chills, malaise, cough, myalgias and
nausea) consistent with influenza A infection. Subjects must not be
symptomatic and be at least 7 days since the resolution of fever, and must
enroll within 12 months of illness.

2. Vaccination with a licensed influenza vaccine and at least 14 days following
the last vaccination in the series, and enrolling within 12 months of
vaccination.

3. Some subjects may meet both requirements and enrollment should be within 12
months of the most recent event (illness or vaccination)

4. Adequate clinical parameters (all of the following):

1. Afebrile (temperature < 38 Degrees C)

2. Systolic blood pressure > 100 and < 180 mmHg

3. Diastolic blood pressure > 50 and < 100 mmHg

4. Heart rate between 50-100 beats/minute (Individual site blood
establishment's SOPs may also permit healthy athletic subjects with heart
rates < 50 beats/minutes to donate plasma, and, if so, subjects with heart
rates < 50 beats/minutes may participate in this study)

5. Weight greater than or equal to 110 pounds (50 kg)

6. Adequate peripheral venous access for plasma donation (as judged by the examiner)

7. Willingness to have samples stored

EXCLUSION CRITERIA:

1. Any sign of active influenza, (as judged by the investigator) including but not
limited to:

1. Subjective or documented fever (> 38 Degrees C)

2. Cough

3. Shortness of breath

4. Diarrhea

2. Has a medical history of

1. Thrombocytopenia or other blood dyscrasias

2. Congestive heart failure

3. Pulmonary hypertension

4. Bleeding diathesis or therapeutic anticoagulation

5. Human immunodeficiency virus (HIV)/AIDS

6. Hepatitis B

7. Hepatitis C

8. Known history of hepatitis after the 11th birthday

9. Trypanosomiasis (Chagas' disease and sleeping sickness)

10. Leishmaniasis (Kala-azar)

11. Filariasis

12. Q fever

13. Yaws

3. History of cancer that meets any one of the following criteria:

1. Leukemia or lymphoma: permanent deferral

2. Melanoma: 10 year deferral (with exception of melanoma-in-situ: defer until
biopsy site is healed)

3. Squamous cell or basal cell cancer of skin: defer until excision site is
healed

4. All other cancers: defer for 2 years since end of treatment

4. Medication history that includes any of the following:

1. Current use of oral or parenteral steroids, high-dose inhaled steroids (>
800 μg/day of beclomethasone dipropionate or equivalent) or other
immunosuppressive or cytotoxic drugs

2. Finasteride (Proscar, Propecia) within the last 1 month

3. Isotretinoin (Accutane) within the last 1 month

4. Acitretin (Soriatane) within the last 3 years

5. Etretinate (Tegison) at any time

6. Dutasteride (Avodart) within the last 6 months

7. Growth hormone made from human pituitary glands at any time

8. Beef insulin from the United Kingdom at any time

9. Warfarin (Coumadin) within the last 1 week

10. Antibiotics within the prior 48 hours

5. Has ever had any of the following:

1. Sexual contact with someone known to have HIV

2. Had a relative with Creutzfeldt-Jakob Disease, or been told that this
disease is inherited within the family

3. Received blood transfusion in the United Kingdom

4. History of receiving money, drugs or other payment for sex

5. History of receiving clotting factor concentrates

6. History of a dura mater graft

7. History of babesiosis

8. For male donors, history of sexual contact with another male

9. Used needles to take drugs, steroids, or other medications not prescribed by
a physician

10. Was born, lived in, had blood donation in or ever had sexual contact with
anyone who lived in Cameroon, Central African Republic, Chad, Congo,
Equatorial Guinea, Gabon, Niger, or Nigeria after 1977

11. History of living 3 or more months total (need not be consecutive) in the UK
from 1980-1996

12. History of living 5 or more years total (need not be consecutive) in Europe
since 1980

13. History of living 6 or more months total (need not be consecutive) on a U.S.
military base in Europe from 1980-1996 (specifically from 1980 through 1990
in Belgium, the Netherlands, or Germany, and from 1980 through 1996 in
Spain, Portugal, Italy, or Greece)

6. Within the 8 weeks prior to enrollment:

a. Was vaccinated with the small pox vaccine, or was in close contact with
someone who was vaccinated (i.e., close family member)

7. Within the 4 months prior to enrollment has had:

a. A blood donation of a double unit of red cells

8. Within the 12 months prior to enrollment has:

1. Received any blood or blood component

2. Donated blood at a paid donation center (donations at a hospital blood
establishment do not apply)

3. History of tattoo application

4. History of unsafe (multiple-use equipment) acupuncture, or piercing
practices

5. Received an organ transplant

6. Received a bone or skin graft

7. Lived with someone who has any type of hepatitis

8. Been incarcerated for more than 72 hours

9. Oral or inhalation use of illegal drugs (i.e., those not prescribed by a
physician)

10. Had or has been treated (with or without confirmatory diagnosis) for
syphilis or gonorrhea

9. Within the last 12 months has had sexual contact with (any of the following):

1. An individual having viral hepatitis

2. A prostitute or anyone else who takes money or drugs or other payment for
sex

3. Anyone who has ever used needles to take drugs, steroids, or anything else
not prescribed by their doctor

4. Anyone who has hemophilia or has used clotting factor concentrates

5. For females, a male who has ever had sexual contact with another male

10. Participation in medical research that includes:

1. Protocols that are currently ongoing or will start during the duration of
this study that require more than 100 mL of blood to be given in any 8-week
period of time

2. Administration of any unlicensed drug within the last 3 months or during the
duration of this study

3. Administration of any unlicensed vaccine within the last 12 months or during
the duration of this study.

11. Subjects that have participated in previous plasma collection or other cell
component collection within the last 3 months may have restrictions to
participation based on the site plasma collection SOP. In this scenario,
discussion should occur with the blood establishment to ensure eligibility to
donate plasma.

PLASMA DONATION CRITERIA (all of the following):

1. Anti-Influenza A HAI titer of 1:160 or greater and H3N2 HAI titer of at least 1:40

2. Adequate laboratory parameters from screening (must meet all of the criteria below)

1. Hemoglobin level of greater than or equal to 12.5 g/dL

2. HCT greater than or equal to 38%

3. Platelets greater than or equal to 150 x 10^3/cubic mm

4. Total serum protein greater than or equal to 6.0 g/dl

5. Quantitative immune globulin levels (all of the following)

1. Ig A greater than or equal to 90 mg/dL

2. Ig G greater than or equal 650 mg/dL

3. Ig M greater than or equal 35 mg/dL

6. Review of other screening labs should ensure no other underlying medical
condition that would increase subject's risk of apheresis.

3. Negative serologic and molecular tests for blood borne pathogens, to include:

1. Anti-HIV-1/2

2. Anti-HTLV-I/II

3. Anti-HCV

4. HBsAg (hepatitis B surface antigen)

5. Serologic test for syphilis (PK-TP)

6. HIV NAT

7. HCV NAT

8. WNV NAT