Development of Immune Globulin Treatment for Avian Flu
Condition: Infectious Diseases; Influenza; Avian Flu
MeSH terms: Influenza, Human; Communicable Diseases; Infections; Influenza in Birds
Intervention: H5N1 vaccine; Apheresis
Intervention description: Monovalent subvirion H5N1 vaccine (rgA/Vietnam/1203/2004) 90 mcg/mL Manufactured by Sanofi Pasteur Inc, Swiftwater, PA.; Once subjects achieved a high antibody titer (>1:160), they could begin apheresis to collect plasma.
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 126.0
Sex: All
Minimum age: 18 Years
Maximum age: 59 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Apheresis; Avian Flu; Healthy Volunteers; Infectious Diseases; IVIG; Healthy Volunteer; HV

Summary:

      This study will determine how best to use a vaccine for generating high levels of antibodies
      called immune globulins (IVIG) in people, which, in turn, can be collected and used to
      develop a possible treatment for avian influenza (bird flu). Immune globulins are proteins
      made by the body that attack the influenza virus. This study will use an experimental bird
      flu vaccine to stimulate immune globulin production in healthy people. The vaccine is similar
      to the regular influenza vaccine and has been studied in more than 450 people. This study
      will use high doses of the vaccine to generate high antibody levels that can be collected for
      producing the new treatment.

      Healthy adults between 18 and 60 years of age who weigh at least 110 pounds may be eligible
      for this study. Candidates are screened with a medical history and physical examination.

      Participants are given one of three doses of the vaccine, depending on when they enter the
      study. The first 25 people enrolled receive a dose of 90 micrograms (mcg). If this dose is
      well tolerated, the next 25 people receive 120 mcg, and if this dose is also well tolerated,
      the last 25 people receive 180 mcg. Vaccination consists of either two shots (one in the
      muscle of each arm) or one shot in the buttock on four occasions. Subjects are vaccinated on
      four occasions, each 4 weeks apart. On the day of each vaccination, subjects provide a blood
      sample to evaluate blood counts, chemistries, and antibody levels, and to test for HIV,
      hepatitis B and C, syphilis, and antibody against avian flu. For 7 days after each
      vaccination, subjects keep a diary card to record any symptoms, such as pain, fever, muscle
      aches, or others. At the end of the 7 days, they are contacted by study staff to report the
      symptoms.

      In addition to the vaccinations, subjects undergo apheresis to collect IVIG once their blood
      test shows moderately high antibody levels. For this procedure, blood is collected through a
      needle in an arm vein and flows through a catheter (plastic tube) into a machine that
      separates the blood cells from the antibodies and protein. The antibodies and protein are
      collected and the rest of the blood is returned to the body. Subjects are asked to undergo at
      least three apheresis procedures.

      ...
    

Eligibility criteria:

        Inclusion Criteria

          1. Age ≥ 18 years old, and < 60 years old.

          2. Adequate clinical parameters (all of the following):

               -  Afebrile (temperature < 38° C)

               -  Systolic blood pressure >100 & <180 mmHg

               -  Diastolic blood pressure >50 & <100 mmHg

               -  Heart rate between 40-100 beats/minute

          3. Weight ≥ 110 pounds (50kg)

          4. Adequate peripheral venous access for plasmapheresis (as judged by the examiner)

          5. Females of child-bearing potential must (one of the following):

               -  Be surgically sterile.

               -  Be abstinent (or willing to be) 4 weeks prior to date of screening evaluation
                  through the last apheresis session (estimate 6 months).

               -  Use oral contraceptives, or other form of hormonal birth control including
                  hormonal vaginal rings or transdermal patches, and have been using these for 3
                  months prior to date of screening evaluation through the last apheresis session
                  (estimate 6 months).

               -  Use an intra-uterine device (IUD) as birth control 4 weeks prior to date of
                  screening evaluation through the last apheresis session (estimate 6 months).

               -  Use (by ensuring her male partner(s) uses) barrier contraception (condom) with a
                  spermicide as birth control 4 weeks prior to date of screening evaluation through
                  the last apheresis session (estimate 6 months).

        Exclusion Criteria:

          1. Has a medical history of

               -  Thrombocytopenia or other blood dyscrasias

               -  congestive heart failure

               -  pulmonary hypertension

               -  bleeding diathesis or therapeutic anticoagulation

               -  HIV/AIDS

               -  Hepatitis B

               -  Hepatitis C

               -  Known history of hepatitis after the 11th birthday.

               -  Trypanosomiasis (Chagas' disease and sleeping sickness)

               -  Leishmaniasis (Kala-azar)

               -  Filariasis

               -  Q fever

               -  Yaws

               -  Allergy to eggs, thimerosal, or other components of the vaccine

               -  Severe reactions following immunization with contemporary influenza virus
                  vaccines

               -  Autoimmune disease or a history of Guillain-Barré

          2. History of cancer that meets any one of the following criteria:

               -  Non-melanoma skin cancers within the last 1 year

               -  Melanoma or any other cancer (excluding non-melanoma skin cancers) at any time

          3. Medication history that includes any of the following:

               -  Current use of oral or parenteral steroids, high-dose inhaled steroids (>800
                  mcg/day of beclomethasone dipropionate or equivalent) or other immunosuppressive
                  or cytotoxic drugs

               -  Finasteride (Proscar, Propecia) within the last 1 month.

               -  Isotretinoin (Accutane) within the last 1 month.

               -  Acitretin (Soriatane) within the last 3 years.

               -  Etretinate (Tegison) at any time.

               -  Dutasteride (Avodart) within the last 6 months.

               -  Growth hormone made from human pituitary glands at any time.

               -  Beef insulin from the United Kingdom at any time.

          4. Has ever had any of the following:

               -  Sexual contact with someone known to have HIV.

               -  Had a relative with Creutzfeldt-Jakob Disease, or been told that this disease is
                  inherited within the family.

               -  Received blood transfusion in the United Kingdom.

               -  History of receiving money, drugs or other payment for sex.

               -  History of receiving clotting factor concentrates.

               -  History of a dura mater graft.

               -  History of babesiosis.

               -  For male donors, history of sexual contact with another male.

               -  Used needles to take drugs, steroids, or other medications not prescribed by a
                  physician.

               -  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.

               -  History of living 3 or more months total (need not be consecutive) in the UK from
                  1980-1996.

               -  History of living 5 or more years total (need not be consecutive) in Europe since
                  1980.

               -  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, Turkey, Italy or Greece).

          5. Within the last 3 weeks received the seasonal (conventional trivalent) flu vaccine

          6. Within the last 8 weeks:

             • 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 last 3 months has:

             • Current or previous participation in any other apheresis procedures/protocols (not
             related to this protocol).

          8. Within the last 4 months has had:

             • A blood donation of a double unit of red cells.

          9. Within the last 12 months has:

               -  Received any blood or blood component.

               -  Donated blood at a paid donation center (donations at a hospital blood bank do
                  not apply).

               -  History of unsafe (multiple-use equipment) tattoo, acupuncture, or piercing
                  practices.

               -  Received an organ transplant.

               -  Received a bone or skin graft.

               -  Lived with someone who has any type of hepatitis.

               -  Traveled to areas with malaria.

               -  Been incarcerated for more than 72 hours.

               -  Oral or inhalation use of illegal drugs (i.e. those not prescribed by a
                  physician).

               -  Had or has been treated (with or without confirmatory diagnosis) for syphilis or
                  gonorrhea

         10. Within the last 12 months has had sexual contact with (any of the following):

               -  An individual having viral hepatitis.

               -  A prostitute or anyone else who takes money or drugs or other payment for sex.

               -  Anyone who has ever used needles to take drugs, steroids, or anything else not
                  prescribed by their doctor.

               -  Anyone who has hemophilia or has used clotting factor concentrates.

               -  For females, a male who has ever had sexual contact with another male.

         11. Participation in medical research that includes:

               -  Protocols that are currently ongoing or will start during the duration of this
                  study that require more than 100cc of blood to be given in any 6-week period of
                  time.

               -  Administration of any unlicensed drug within the last 3 months or during the
                  duration of this study.

               -  Administration of any unlicensed vaccine within the last 12 months or during the
                  duration of this study.

         12. Currently pregnant (if known).

         13. Any condition that, in the opinion of the investigator, would render vaccination
             unsafe, would interfere with the antibody response or the evaluation of these
             responses, or would place the subject at increased risk of injury from apheresis.