healthy volunteers (protection against influenza) MedDRA version: 16.1 Level: LLT Classification code 10016794 Term: Flu vaccination System Organ Class: 100000004865
Conditions
Interventions
Trade Name: Flucelvax
Pharmaceutical Form: Suspension for injection in pre-filled syringe
INN or Proposed INN: A/ (H1N1)-LIKE VIRUS ANTIGEN
Other descriptive name: A/ (H1N1)-LIKE VIRUS ANTIGEN
Concent
Sponsors
Novartis Vaccines & Diagnostics AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is a healthy subject, male or female, 6 through =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Has parent(s) or legal guardian(s) who are not able to comprehend and to follow all required study procedures for the duration of the study 2. Has parent(s) or legal guardian(s) who are not able to read or write and are not able to delegate a designated person (information of whom will be entered in the study file) who: a. Is an impartial person of legal age who is willing and able to witness the informed consent procedures as required by the protocol, b. Is willing and able to undergo Diary Card training, and c. Is willing and able to collect information on the Diary Card on a daily basis during the Post-vaccination Period through day 50 per protocol requirements; 3. Is a child from whom the minimal blood volume cannot be obtained prior to randomization, at the discretion of the investigator 4. Known or suspected impairment/alteration of immune function, including: a. Long-term oral or parenteral corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) b. Any history of cancer chemotherapy c. Receipt of immunostimulants within 60 days prior to day 1 d. Receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to day 1 or planned during the full length of the study e. Known HIV infection or HIV-related disease 5. Has a history of Guillain–Barré syndrome 6. Has a bleeding disorder that would be a contraindication to intramuscular injection 7. Has a history of non-febrile seizures 8. Has a history of or clinically suspected developmental delay 9. Has a history of premature birth (<36 weeks of gestation) and/or low birth weight (<2.5 kg) 10. Had laboratory-confirmed influenza disease within 6 months prior to visit 1 11. Has received an antipyretic or analgesic in the past 24 hours prior to vaccination 12. Has medical history or any illness that, in the opinion of the Investigator, might interfere with the results of the study or pose additional risk to the individual because of participation in the study 13. Has a history of any anaphylactic reaction and/or serious allergic reaction to any component of the study vaccine (see section 5.1) 14. Has experienced acute disease and/or fever (i.e., body temperature measurement =38.0°C [=100.4°F]) within 3 days prior to vaccination. 15. Has been participating in any clinical trial with another investigational product 4 weeks prior to first study visit or intends to participate in another clinical study at any time during the conduct of this study 16. Is the child of research staff involved with the clinical study at this institution or is otherwise related to research staff or has household members who are research staff associated with the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Immunogenicity Objective To select an optimal dose of TIVc for pediatric subjects 6 to < 48 months of age by desirability index score (The overall desirability index is based on comparison of post-vaccination haemagglutination inhibition (HI) assay results and specific solicited adverse events following any vaccination);Secondary Objective: Key Secondary Immunogenicity Objective - To evaluate HI antibody responses to each study vaccine (TIVc and TIVe) according to CBER immunogenicity criteria in pediatric subjects Secondary Immunogenicity Objectives - To evaluate HI antibody responses to each study vaccine according to CHMP immunogenicity criteria in pediatric subjects - To evaluate antibody responses to each study group by microneutralization (MN) assay in pediatric subjects - To evaluate geometric mean titer (GMT) percentages of subjects with higher titers by HI assay, and reverse cumulative distribution function curves of HI antibody responses for each vaccine group in pediatric subjects -To perform pairwise comparisons between vaccine groups of post-vaccination GMT by HI and MN assay and between vaccine groups for seroconversion by HI assay Safety Objective To evaluate the safety and tolerability of each study vaccine in pediatric subjects 6 to < 48 months of age.;Primary end point(s): Primary Endpoint - Identification of the optimal dosage of TIVc The overall desirability index is defined as the weighted geometric mean of individual desirability indexes based on the following key immunogenicity and safety parameters: 1) Ratios of geometric mean titer (GMT) between each of TIVc dose group vs. TIVe 2) Differences in percentages of subjects achieving seroconversion (SC) by HI antibody titer in each TIVc group vs. TIVe 3) Percentages of subjects described as having severe local solicited AEs 4) Percentages of subjects described as having severe local systemic AEs Desirability index scoring will be based on the results obtained fr | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: See above;Secondary end point(s): CBER criteria Antibody responses to the study vaccine in subjects 6 to < 48 months of age will be evaluated by HI assay according the CBER immunogenicity criteria (CBER 2007). CHMP criteria Antibody responses to the all the vaccine groups in the age groups defined above will be evaluated by HI assay according to CHMP immunogenicity criteria specified in Guidance on Harmonization of Requirements for Influenza Vaccines (CPMP/BWP/214/96). In the absence of guidance for the assessment of immunogenicity in pediatric subjects, immunogenicity of each vaccine group will be evaluated according to criteria defined for adults. High HI titer analyses Antibody responses to the all the vaccine groups in the age groups defined above will be evaluated by percentages of subjects achieving specific HI titer threshold values as follows: =1:110, =1:151, =1:330, =1:629. These titers have been associated within potential for increased protection against confirmed influenza in a recent publication (Black 2011). Pairwise comparisons Ratios of geometric mean titer (GMT) between each of TIVc dose group vs. TIVe (A/B, A/C, A/D, B/C, B/D, C/D) for HI and MN assays. Differences in seroconversion rates at Day 50 between each of TIVc dose group vs. TIVe (A/B, A/C, A/D, B/C, B/D, C/D) by HI assay only. Endpoint in terms of MN titers - Percentage of subjects achieving post-vaccination MN titer =1:20 for subjects with baseline (day 1) MN titer <1:10, or a minimum 2-fold increase in titer on day 50 for subjects with baseline titer =1:10 and corresponding 95% CI - Percentage of subjects achieving post-vaccination MN titer =1:40 for subjects with baseline (day 1) MN titer <1:10, or a minimum 4-fold increase in titer on day 50 for subjects with baseline titer =1:10 and corresponding 95% CI RCDF Reverse cumulative distribution function curves of HI and MN titers at Day 50 post-vaccinationpost-vaccination | — |
Countries
Finland, Philippines, Thailand, United States
Contacts
Public ContactTerhi Hirvonen
Novartis Vaccines & Diagnostics, Clinical Development Global Monitoring Organization CNE
Outcome results
None listed