E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The intended indication for the IMP GHB16L2 is prevention of influenza A (H1N1, H3N2) and B contained in the vaccine. |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess safety and tolerability of single dose of GHB16L2 |
|
E.2.2 | Secondary objectives of the trial |
To assess
- immunogenicity (HAI, MNA, SRH, IgA, Granzyme B T-cell response)
- pharmacokinetics (shedding) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Healthy male and female volunteers, 18-60 years
• Seronegative for one or two of the applied vaccine strains (with antibody titres ≤1:16 detected in micro-HAI assay for influenza A/Brisbane/59/07(H1N1), A/Brisbane/10/07(H3N2) and/or B/Florida/04/06
• Low antibody titres (i.e. titres ≤1:64 detected in micro-HAI assay) for H1N1v
• Written informed consent to participate in this study
• For female volunteers of childbearing potential, provision of a history and current use of reliable contraceptive practices (hysterectomy or bilateral tubal ligation, oral or implanted contraceptive use, intrauterine device, barrier method plus spermicide, history of a single male partner with vasectomy, or a history of abstinence deemed credible by the investigator). Note: The provision of this history does NOT replace the requirement to perform, and obtain negative results in pregnancy tests. |
|
E.4 | Principal 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 in 2008/2009 and/or later seasons and/or pandemic influenza vaccination at any time
• Fever ≥38.0°C in the time period between the pre-screening visit and day 1
• Known increased tendency of nose bleeding
• Volunteers with clinically relevant abnormal paranasal anatomy
• Volunteers with clinically relevant abnormal laboratory values
• In female volunteers of childbearing potential, a positive urine pregnancy test
• 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 4 weeks prior to study medication application
• Volunteers who have received anti-inflammatory drugs 2 days prior to study medication application |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is to assess the safety and tolerability of GHB16L2 administered as a single dose liquid nasal spray against influenza A (H1N1, H3N2) and B virus. For this purpose 80 healthy volunteers are planned to be included in a phase I/II study where a first group of 18 volunteers and consecutively a second group of 62 volunteers will be randomized in a ratio of 1:1 for verum or placebo in parallel. The second group of 62 will only be included after the safety observation period and an interim safety review for the first group of 18 has been completed. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
To assess the immunogenicity (HAI, MNA, SRH, IgA, IgG and Granzyme B T-cell response) and pharmrcokinetics of GHB16L2 administered as a single dose liquid nasal spray against influenza A (H1N1, H3N2) and B virus. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
LVLS - Last visit of last subject undergoing the trial |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |