| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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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 evaluate the immunogenicity of CSL412 in Older Adults (aged ≥ 60 years) against the immunogenicity criteria of the CPMP/BWP/214/96 Note for Guidance on Harmonisation of Requirements for Influenza Vaccines.
To evaluate the safety and tolerability of CSL412 as compared to active comparator vaccine. |
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| E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of CSL412 in terms of solicited local and general adverse events, unsolicited adverse events and serious adverse events
Exploratory Objectives: To compare the T cell response in Older Adults vaccinated with CSL412 to the T cell response in Adults and Older Adults vaccinated with unadjuvanted trivalent inactivated influenza vaccine. To compare the T cell response in Older Adults vaccinated with CSL412 to the T cell response in Adults vaccinated with CSL412 |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
All Cohorts:
1.Provision of written informed consent to participate in the study and willingness to adhere to all protocol requirements prior to any study procedures;
2.Ability to provide a pre-vaccination venous blood sample of up to 66 mL without undue distress/discomfort. Participants must not have donated blood within the 3 months prior to Screening.
Healthy Adult Cohort: Cohort A Additional Inclusion Criteria:
1.Healthy males or females, aged ≥ 18 to ≤ 45 years at the time of providing informed consent;
2.Negative urine pregnancy test at enrolment before receiving Study Vaccine (Female participants of childbearing potential ONLY – defined as not surgically sterilised or less than one year post-menopausal). Those at risk of pregnancy or males at risk of causing pregnancy during the active study period must, in the opinion of the PI/delegate, be taking/using adequate methods of contraception. Adequate methods are defined as:
· Oral contraception
· Intrauterine contraceptive device
· Depot contraceptive (implants/injectables)
· Abstinence
· Partner Vasectomy
· Condoms with spermicide
Older Adult Cohort ≥ 60 to < 75 yrs: Cohort B Additional Inclusion Criteria:
1.Community dwelling males or females, aged ≥ 60 and <75 years at the time of providing informed consent.
Older Adult Cohort ≥ 75 yrs: Cohort C Additional Inclusion Criteria:
1.Community dwelling males or females, aged ≥ 75 years at the time of providing informed consent.
Older Adult Long-term Care Facility Cohort: Cohort D Additional Inclusion Criteria:
1.Males or females, aged ≥ 60 years at the time of providing informed consent, resident in long-term care facility (providing some degree of assisted care).
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| E.4 | Principal exclusion criteria |
1.Have a known allergy to eggs, chicken protein, neomycin, polymyxin, any other component in the study vaccines, or previous influenza vaccinations.
2.Have a history of, are suspected of having, or have active and clinically significant hepatic, immunodeficiency (including congenital or acquired), haematological, or autoimmune disorders; or have active infections, especially chronic infections (including tuberculosis, HIV infection or chronic hepatitis B or C infection).
3.Have a history of, are suspected of having, or have had cancer with metastatic disease, or have a primary cancer that has been untreated or not adequately treated. Specifically, participants must not have been treated with cytotoxic drugs or radiotherapy at any time during the six months prior to study entry. Participants with a history of breast or prostate cancer who are undergoing hormonal therapy (such as with tamoxifen or diethylstilbesterol) following adequate treatment of the primary disease may be enrolled. Participants with locally treated skin cancers without metastatic spread may also be enrolled.
4.Have active and clinically significant gastrointestinal, renal, neurological, cardiovascular, respiratory, or endocrine disorders; if
· The Investigator feels the condition may adversely affect the participant through study participation; or
· The Investigator feels that the condition is not currently well controlled/stable.
5.Have any abnormal liver function test (LFT) measure including:
· ALT or AST; increase in factor of > 2.5 x ULN
· Bilirubin – when accompanied by any increase in LFT; increase by factor of > 1.25 x ULN
· Bilirubin – when LFT is normal; increase by factor of > 1.5 x ULN
Note: Participants with Gilbert’s syndrome may be eligible for enrolment
6.Have abnormal renal function as defined by a creatinine level > 0.13 mmol/L.
7.Have been vaccinated against influenza in 2007.
8.Have an abnormally low platelet count, with a platelet count <=140x10-9/L
9.Have participated in a clinical trial where they received an investigational product, or use of an investigational compound (i.e. a new chemical or biological entity not registered for clinical use) within 30 days prior to receiving the Study Vaccines, or plans to enter a clinical trial during the study period;
10.Have been vaccinated with a registered vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to study entry;
11.Be undergoing current (or within the 90 days prior to receiving the Study Vaccines) immunosuppressive or immunomodulative therapy, including systemic corticosteroids, as follows:
· Chronic or long term corticosteroids: >= 15 mg/day of oral prednisolone or equivalent daily;
· Sporadic corticosteroids: >= 40 mg/day of oral prednisolone or equivalent for two or more short courses of > 3 days in the three months preceding vaccination;
· Administration of immunogobulins and/or any blood products within the 3 months preceding study entry or during the study
Note: Use of topical or inhalant corticosteroids prior to administration of the Study Vaccines or throughout the Study is acceptable.
12.Be undergoing current treatment with warfarin or other anticoagulants, however, patients on anti-platelet agents, including low-dose aspirin, ticlopidine (Ticlid) and clopidogrel (Plavix) may be enrolled.
13.Have a known history of Guillain-Barré Syndrome.
14.Have evidence, or history of (within the previous 12 months) drug or alcohol abuse;
15.Have clinical signs of active infection and/or an oral temperature of >=38°C at the time of vaccination (Note: vaccination may be deferred for such individuals, at the discretion of the Principal Investigator).
16.Be unwilling/unable to comply with the protocol.
17.Have any medical, psychiatric, or social condition that in the opinion of the Principal Investigator would prevent the participant from giving proper informed consent and complying with the study protocol, or make it unsafe to receive the study vaccine.
18.Have Human Immunodeficiency Virus (HIV) infection or a positive test for HIV antibodies on either ELISA or Western Blot test.
19.Have acute hepatitis B infection, or chronic hepatitis B infection as indicated by a positive test for hepatitis B surface antigen.
20.Have hepatitis C infection or a positive test for hepatitis C antibodies.
21. Lactating women
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The immune response to influenza haemagglutinin antigens (measured by serum HI antibody assay) following vaccination with CSL412, evaluated as:
1. Seroprotection rate: the proportion of participants achieving post vaccination HI titres >= 40.
2. The geometric mean of the fold increase in HI titre post-vaccination.
3. Seroconversion or significant increase rate: the proportion of participants achieving seroconversion (pre-vaccination HI titre < 10 and post vaccination HI titre >= 40) or significant increase in HI titre (pre vaccination HI titre >= 10 and >=4-fold increase in HI titre post-vaccination).
4.Each strain should meet at least one of the three CPMP immunogenicity requirements for Older Adults (>= 60 years), namely: Seroprotection rate > 60%, GM Fold increase > 2.0, or seroconversion/significant increase rate > 30%.
5.Rate of occurrence of study vaccine-associated Grade 3 or higher fever,or study vaccine-associated vaccination site ulceration,abscess or necrosis |
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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 | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| 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) | 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 7 |
| 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 | Yes |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 12 |
| E.8.9.1 | In the Member State concerned days | |
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