Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Double-blind, Placebo-controlled, Phase I Dose-escalation Study of Single Dose GHB01L1 in Healthy Volunteers
Brief Summary: The purpose of this phase I trial is to evaluate safety and tolerability of GHB01L1 administered as single dose intranasal aerosol for vaccination against influenza A (H1N1) virus.

This study is performed further to assess local and systemic immune response and to analyse pharmacokinetics (shedding) of a single dose GHB01L1 aerosol administered intranasally.


Options:
A: Inclusion Criteria:

* Subjects 18 years of age and older who were mentally competent and who had signed an informed consent form after having received a detailed explanation of the study protocol;
* In good health as determined by:

  1. medical history,
  2. physical examination,
  3. clinical judgment of the Investigator;
* Able to understand and comply with all study procedures and to complete study diaries, could be contacted, and were available for study visits;

Exclusion Criteria:

* Receipt of another investigational agent within 4 weeks;
* Laboratory-confirmed influenza disease within 6 months prior to Visit 1;
* Receipt of influenza vaccination for current season 2008/2009;
* Experienced any acute disease or infection requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis was acceptable) within the past 7 days;
* Experienced fever (defined as axillary temperature ≥38.0°C) within 7 days prior to Visit 1;
* Pregnant or breastfeeding;
* Females of childbearing potential who were sexually active and had not used or did not plan or refused to use an acceptable method of birth control during the active phase of the study (at least up to three weeks after last vaccine injection);
* Any serious disease, such as: cancer, autoimmune disease (including rheumatoid arthritis); diabetes mellitus type I and type II; diabetes relating to genetic defects/syndromes, diseases of the exocrine pancreas or infections; advanced arteriosclerotic disease; severe chronic obstructive pulmonary disease (COPD), i.e. GOLD stages 3 and 4; acute or progressive hepatic disease and renal disease; congestive heart failure; Body Mass Index (BMI) ≥35 kg/m2 where BMI reflects obesity and not high muscle mass;
* History of progressive or severe neurologic disorders, of any neurological symptoms or signs, or anaphylactic shock following administration of any study vaccine;
* Bleeding diathesis;
* Surgery planned during the study period;
* Hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein, neomycin or polymyxin or any other component of the study vaccines;
* Known or suspected impairment/alteration of immune function, for example, resulting from:

  1. receipt of immunosuppressive therapy (any corticosteroid therapy or cancer chemotherapy) or other immunosuppressive agents within the past 60 days and for the full length of the study;
  2. receipt of immunostimulants;
  3. receipt of parenteral immunoglobulin preparation, blood products and/or plasma derivates within the past 3 months and for the full length of the study;
  4. suspected or known HIV infection or HIV-related disease;
* Receipt of non study vaccines (with the exception of post-exposure vaccination in a medical emergency, e.g. hepatitis, rabies, tetanus) within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination;
* History of (or current) drug or alcohol abuse that in the investigator's opinion would interfere with safety of the subject or the evaluation of study objectives;
* Members of research staff and their relatives;
* Any condition, which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.
B: Inclusion Criteria :

* Healthy adults aged 18 years or older on the day of inclusion
* Informed consent has been signed and dated
* Able to attend all scheduled visits and comply with all trial procedures
* For a woman of child-bearing potential, use of an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination, until at least 4 weeks after last vaccination.

Exclusion Criteria :

* Known pregnancy or positive urine pregnancy test
* Currently breastfeeding a child
* Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination
* Planned participation in another clinical trial during the present trial period
* Receipt of any vaccine in the 4 weeks preceding the trial vaccination
* Planned receipt of any vaccine prior to the Day 42 blood sample
* Receipt of blood or blood-derived products in the past 3 months which might interfere with the assessment of immune response
* Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
* Self-reported seropositivity for Human Immunodeficiency Virus (HIV), Hepatitis B antigen, or Hepatitis C
* Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances
* Self reported thrombocytopenia contraindicating intramuscular (IM) vaccination
* Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion contraindicating IM vaccination
* Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
* Current alcohol abuse or drug addiction that may interfere with the subject's ability to comply with trial procedures
* Chronic illness that in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion
* Employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members of the employees or the Investigator.
* Previous participation in a swine-origin H1N1 pandemic flu trial except if performed in 1976
* Any confirmed case of influenza (including swine-origin A/H1N1 Influenza) since March 2009
* Febrile illness (temperature ≥ 100.4°F \[≥ 38.0°C\]) or moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination
* Personal or family history of Guillain-Barré syndrome
* Active neoplastic disease or a history of any hematologic malignancy
* Known seizure/epilepsy history and/or taking anti-seizure medication
* Receipt of psychiatric drugs. Subjects receiving a single antidepressant drug and stable for at least 3 months prior to enrollment, without decompensating symptoms will be allowed to enroll in the study
C: Inclusion Criteria:

* Healthy male volunteers, 18-50 years
* Immune status: seronegative with respect to the applied virus antigens with antibody titres \<1:10 detected in the HAI assay with the corresponding antigens)
* Written informed consent to participate in this study

Exclusion Criteria:

* Acute febrile illness (\>37.3°C)
* Signs of acute or chronic upper or lower tract respiratory illnesses (sneezing, cough, tonsillitis, otitis etc.)
* History of severe atopy
* Seasonal influenza vaccination 2005/2006, 2006/2007 and/or 2007/2008 and/or pandemic influenza vaccination against H5N1
* Known increased tendency of nose bleeding
* Volunteers with clinically relevant abnormal paranasal anatomy
* Volunteers with clinically relevant abnormal laboratory values
* Simultaneous treatment with immunosuppressive drugs incl. Corticosteroids (≥2 weeks) within 4 weeks prior to study medication application
* Clinically relevant history of renal, hepatic, GI, cardiovascular, haematological, skin, endocrine, neurological or immunological diseases
* History of leukaemia or cancer
* HIV or Hepatitis B or C seropositivity
* Volunteers who underwent rhino or sinus surgery, or surgery of another traumatic injury of the nose within 30 days prior to application of study medication
* Volunteers who have received antiviral drugs, treatment with immunoglobulins or blood transfusions, or an investigational drug within four weeks prior to study medication application
* Volunteers who have received anti-inflammatory drugs 2 days prior to study medication application
* Volunteers who are not likely to cope with the requirements of the study or with a significant physical or mental condition that may interfere with the completion of the study
D: Inclusion Criteria:

* Persons must be adult men and women aged 18-49 years.
* Persons must be able and willing to provide informed consent.
* Persons must expect to reside in the study area during the entire study period and be interested in participating each year.
* Persons must be willing to receive the licensed live-attenuated vaccine (FluMist) or placebo given as a nasal spray, or the licensed inactivated influenza vaccine (Fluzone or Fluvirin) or placebo given as an intramuscular injection.
* Persons must be willing to provide multiple blood specimens collected by venipuncture each year they are in the study. During each of the first two years of study, blood specimens will be collected three times - at the enrollment visit (immediately prior to administration of vaccine or placebo), at the first follow-up visit 3-5 weeks later, and at the end of the influenza season visit (approximately 4-6 months later); during the third year of the study, blood specimens will be collected twice only, at visits before and after the influenza season.
* Persons must be willing to notify study personnel in the event of influenza-like illness, to provide information on illness symptoms, and to permit collection of a throat culture (swab) specimen for laboratory studies.
* Persons must be willing to not receive an influenza vaccine while participating - other than that (influenza vaccine or placebo) received as study medication.

Exclusion Criteria:

* Persons with any health condition for which the inactivated vaccine is recommended (Advisory Committee on Immunization Practices - ACIP) including: chronic diseases of the pulmonary or cardiovascular systems (including asthma); chronic metabolic diseases (including diabetes); renal dysfunction; hemoglobinopathies; immune deficiency disease (including HIV infection) or on-going immunosuppressive therapy.
* Persons who are currently pregnant, nursing mothers or planning a pregnancy within one month of vaccination.
* Persons with hypersensitivity to egg, egg protein, thimerosal (a preservative) or the antibiotic Gentamicin (also know as Garamycin).
* Persons who have had a prior serious reaction to influenza vaccine, or ever had Guillain-Barre syndrome.
* Persons who are living in a household with or have direction occupational contact with immunosuppressed individuals (including health care workers with direct patient contact).
* Persons who have received an influenza vaccine for the influenza season in which they are to be first enrolled or those who plan to receive an influenza vaccine during their participation in the study - other than that (influenza vaccine or placebo) received as study medication.
* Persons who have received any other vaccine within one week prior to enrollment (may delay enrollment).
* Persons who have had a respiratory illness or illness with fever within 3 days of study enrollment (may delay enrollment).
* Persons who are participating in another research study involving any study medications (medicines or vaccines).

Answer: C