E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immunization against A/California/7/2009 (H1N1)v-like influenza in male and female subjects aged 18 years and above. |
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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 demonstrate that vaccination with two doses of the H1N1 candidate vaccine (A/California/7/2009 (H1N1)v-like strain) containing 1.9 µg of HA adjuvanted with AS03A results in an Haemagglutination Inhibition (HI) immune response to the vaccine-homologous virus that meets or exceeds the EMEA (CHMP) guidance targets for pandemic vaccine seroconversion rate (SCR), seroprotection rate (SPR), and geometric mean fold rise (GMFR) at 21 days after the second dose of H1N1 vaccine in adults within the 18 to 60 years and above 60 years age strata. |
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E.2.2 | Secondary objectives of the trial |
To assess whether vaccination with the H1N1 candidate vaccine antigen containing 1.9 µg of HA with AS03A results in an HI immune response to the vaccine-homologous virus that meets or exceeds CHMP guidance targets for pandemic vaccine 21 days after the first dose of H1N1 vaccine in adults above 18 years. To describe the immunogenicity to vaccine-homologous H1N1v-like antigen in terms of HI at Day 0, 21, 42, 182 and 364 in adults above 18 years. To describe the immunogenicity to H1N1v-like antigen at Day 0, 21, 42, 182 and 364 in terms of neutralizing antibodies in adults in a subset of subjects above 18 years. To describe the safety of the vaccine regimens in terms of solicited AEs, 7 days post-vaccination; unsolicited AEs, 21 days post-dose 1 and 63 days post-dose 2; AESIs for the entire study period, SAEs and biochemical parameters at Day 0, 21, 42, 182 and 364.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• A male or female aged 18 years or above at the time of the first vaccination. • Subjects who the investigator believes that they can and will comply with the requirements of the protocol (e.g. comprehension of the study requirements, ability to comprehend and comply with procedures for collection of safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits). • Written informed consent obtained from the subject. • Satisfactory baseline medical assessment by history and physical examination (stable health status with no exclusionary medical or psychiatric conditions). Stable health status is defined as the absence of a health event satisfying the definition of a serious adverse event, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within one month prior to enrolment. • Access to a consistent means of telephone contact, which may be either in the home or at the workplace, land line or mobile, but NOT a pay phone or other multiple-user device (i.e., a common-use phone serving multiple rooms or apartments). • Female subjects of non-childbearing potential may be enrolled in the study. • Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause. Please refer to the Glossary of Terms for the definition of menarche and menopause. • Female subjects of childbearing potential may be enrolled in the study, if the subject: • has practiced adequate contraception for 30 days prior to vaccination, and • has a negative pregnancy test on the day of vaccination, and • has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
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E.4 | Principal exclusion criteria |
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of the study vaccine or planned use during the study period. Potential subjects in the follow-up (i.e., no treatment) phase of a prior investigational study may be enrolled if the investigator’s judgment is that it will have no effect on safety, reactogenicity, or immunogenicity endpoints in this study, and that it does not violate the protocol requirements of the prior trial. • Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. • Presence of an axillary temperature ≥ 37.5ºC, or acute symptoms greater than “mild” severity on the scheduled date of first vaccination. NOTE: The subject may be vaccinated at a later date, provided symptoms have resolved, vaccination occurs within the window specified by the protocol, and all other eligibility criteria continue to be satisfied. • Diagnosed with cancer, or treatment for cancer, within the past 3 years. • Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible. • Persons with a history of histological-confirmed basal cell carcinoma of the skin successfully treated with local excision only are excepted and may enrol within 3 years of diagnosis, but other histological types of skin cancer require a 3 year untreated and disease-free window as above. • Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylactic hormonal therapy are excepted and may enrol. • Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection. • Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune modifying drugs within 6 months of study enrolment or planned administration during the study period. For corticosteroids, this will mean a dose equivalent to 20 mg/day of prednisone when administered for > 2 weeks. Inhaled and topical steroids are allowed. • Receipt of any immunoglobulins and/or any blood products within 3 months of study enrolment or planned administration of any of these products during the study period. • Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin outside of 24 hours prior to vaccination are eligible. Persons receiving prophylactic antiplatelet medications, e.g., low-dose aspirin, and without a clinically-apparent bleeding tendency, are eligible. • An acute evolving neurological disorder or history of Guillain-Barré syndrome. • Clinically or virologically confirmed influenza infection within 6 months preceding the study start. • Administration of any vaccines within 30 days before vaccination. • Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. • Pregnant or lactating female • Female planning to become pregnant or planning to discontinue contraceptive precautions. • Any conditions which, in the opinion of the investigator, prevents the subjects from participating in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Humoral immune response in terms of Haemagglutination Inhibition (HI) antibodies. In subjects receiving two doses of 1.9 µg of A/California/7/2009 (H1N1)v-like vaccine adjuvanted with AS03A • SCR* at 21 days after second dose of H1N1 vaccine (Day 42) • SPR** at 21 days after second dose of H1N1 vaccine (Day 42) • GMFR*** at 21 days after second dose of H1N1 vaccine (Day 42)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
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 | Information not present in EudraCT |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |