Safety Trial of Monovalent Whole Virus Influenza (H1N1) Vaccine
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      The study hypothesis is that two 0.5 ml doses of non-adjuvanted whole virion monovalent
      A/H1N1 influenza vaccine (IVACFLU)--each dose with an HA content of 15 mcg from
      A/California/07/2009 (H1N1)-like virus--will be safe and immunogenic in healthy adults.
    

Detailed description: 
      This is a phase I, double-blind, individually-randomized (1:1, vaccine:placebo), controlled
      trial with two groups, IVACFLU (A/H1N1) and placebo. Healthy male and female adults 18
      through 40 years of age will be invited to participate. In addition to sponsor monitoring of
      safety, Program for Appropriate Technology in Health (PATH) will review safety data. Safety
      data through 7 days post-dose one for all subjects will be reviewed in a blinded fashion
      prior to administration of dose two of study vaccine or placebo. PATH will review all adverse
      events (AEs), including clinical laboratory evaluations (pre- and post-vaccination) and will
      advise if the volunteers may receive dose two of study vaccine or placebo. For all subjects,
      the procedures and timelines are summarized below.

      On the day of first screening (S1), about 14 days (between 5 and 30 days) prior to
      administration of dose one of study vaccine or placebo, subjects will be screened for
      eligibility through medical history review, physical examination, testing for serologic
      evidence of chronic viral infection [human immunodeficiency virus (HIV), hepatitis B virus
      (HBV) or hepatitis C virus (HCV)], routine biochemical and hematological blood tests and
      urinalysis by dipstick. For screening for serologic evidence of chronic viral infections,
      appropriate pre- and post-test counseling must be provided.

      Subject screening for eligibility will continue and be completed on the second screening day
      (S2). This second screening day will occur the same day as scheduled enrollment into the
      trial and administration of study vaccine or placebo (Day 0). Women will undergo pregnancy
      tests using urine samples on Day 0. Fully eligible subjects will be enrolled into the trial.
      At that time, blood specimens will be collected for immunological testing prior to
      administration of study vaccine or placebo. Subjects will be unaware of which allocation,
      IVACFLU or placebo, is received; study vaccine and placebo will be masked. Subjects will be
      carefully monitored for adverse reactions for 60 minutes after vaccination.

      During the first week following vaccination, subjects will be asked to record local and
      general signs and symptoms using preprinted diary cards, thermometer, and small ruler.
      Concomitant medications will also be recorded. In addition to solicited signs, subjects will
      be asked to report any other adverse events, whether or not they believe that the event is
      related to the vaccination. Member of the investigator's clinical team will visit subjects
      one and five days after vaccination to check that subjects are correctly completing the diary
      card and to check on the subjects' well-being. Subjects will then return to the study clinic
      7 days after dose one. At that time, the investigator will check the subjects' diary cards
      and transcribe all adverse events onto the case report forms using medical language. Blood
      and urine specimens will also be collected for routine biochemical and hematological blood
      tests and urinalysis by dipstick.

      Two days before subjects are scheduled to receive dose two, subjects will be visited or
      called to remind them of the next visit to the study clinic and to check on the subjects'
      well-being. Subjects will return to the study clinic at 3 weeks after administration of dose
      one of study vaccine or placebo in order to receive dose two. At that time, interim histories
      and concomitant medications will be reviewed. Women will again undergo urine pregnancy tests.
      All subjects will undergo collection of blood and urine specimens for routine biochemical and
      hematological blood tests and urinalysis by dipstick and collection of blood serum specimens
      for immunologic analyses. Then subjects will receive dose two of study vaccine or placebo and
      be monitored for 60 minutes.

      After receipt of dose two, subjects will again complete diary cards for 7 days after
      vaccination with visits by members of the investigator's clinical team again at days one and
      five after vaccination to check that the subjects are correctly completing diary cards and to
      check on the subjects' well-being. Subjects will then return to the study clinic 7 days after
      dose two (Day 28) for review of diary cards by the investigator and collection of blood and
      urine specimens for routine biochemical and hematological blood tests and urinalysis by
      dipstick.

      Two days before the subjects' next scheduled visit at 3 weeks after administration of dose
      two, subjects will be visited or called to remind them of the next visit to the study clinic
      and to check on the subjects' well-being. Subjects will then return to the study clinic at 3
      weeks after administration of dose two (Day 42) of study vaccine or placebo for another study
      visit. At that time, interim histories and concomitant medications will again be reviewed and
      final blood specimens will be collected for immunogenicity analyses. Women will also undergo
      a final pregnancy screen.

      Subjects will then be asked to immediately report severe adverse events (SAEs) which occur
      from Day 42 to Day 201 (approximately 6 months after receipt of dose two). To facilitate this
      reporting, a member of the investigator's team will visit or call the subjects monthly to
      check on their well-being. At last study visit on Day 201, subjects will be interviewed and
      examined one last time before completing the study.

      For the evaluation of serum antibodies (by hemagglutination inhibition and
      microneutralization), serum specimens will be collected on Day 0 (prior to administration of
      dose one of study vaccine or placebo), on Day 21 (prior to administration of dose two of
      study vaccine or placebo) and on Day 42.
    

Intervention name(s): IVACFLU; Placebo
Intervention type(s): Biological; Other
Intervention description(s): IVACFLU is a whole virus vaccine, collected in a linear sucrose density gradient solution using a continuous flow centrifuge Alfpa Wassmann and inactivated with formaldehyde. It was formulated to contain 15 mcg hemagglutinin (HA) of influenza A/California/07/2009(H1N1)-like virus per 0.5 mL dose and filled in single dose vials.; Phosphate buffered saline (PBS), pH 7.2, in 0.5 ml single-dose vials.
Other intervention name(s): whole virion monovalent A/H1N1 influenza vaccine
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention