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TIV

Phase 3

Seasonal Influenza | Monoclonal antibody | Infectious Disease |Novartis AG|Last Updated: Mar 12, 2014

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLED
Total Trials1
Total Enrollment3,116

FDA Designations

No designations recorded

Clinical trial landscape

TIV · 2 trials · 2 indications

Phase 3 1Phase 2 1
NCT01209780Safety and Immunogenicity of Trivalent Subunit Inactivated Flu Vaccine Administered to Healthy Children and Adolescents 3 to 17 Years of AgeSeasonal Influenza
COMPLETED3,116 Analytics
PHASE3COMPLETED
Safety and Immunogenicity of Trivalent Subunit Inactivated Flu Vaccine Administered to Healthy Children and Adolescents 3 to 17 Years of Age
Seasonal InfluenzaUnlock trial analytics

Study Endpoints

Primary Endpoints

Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion
Day 22 for non-naive/Day 50 for naive subjects

The non-inferiority of the antibody responses of investigational TIV compared to control TIV assessed in terms of the percentage of subjects achieving seroconversion, against the three homologous vaccine strains,in children 3 to 8 years of age, at 21 days after last vaccination. Seroconversion was defined as a pre-vaccination haemagglutinin inhibition (HI) titer \<1:10 and post-vaccination HI titer ≥1:40 or as a pre-vaccination HI titer ≥1:10 and at minimum four-fold rise in post-vaccination antibody titer

Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs)
Day 22 for non-naive/Day 50 for naive subjects

The non-inferiority of the antibody responses of investigational TIV compared to control vaccine assessed in terms of post vaccination GMTs, at 21 days after last vaccination against the three homologous vaccine strains in 3 to 8 year old children.

Percentages of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of TIV
Day 1 (baseline) and Day 22 (postvaccination)

Immunogenicity was assessed in terms of percentages of subjects in both age groups with SRH areas ≥25mm2 against each of the three vaccine strains, three weeks after receiving one dose of TIV . The related European Committee for Human Medicinal Products (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is \>70% for adults aged 18 to ≤60 years and \>60% for subjects aged ≥61 years.

Percentages of Subjects With Seroconversion or Significant Increase in SRH Area, Against Each of Three Vaccine Strains After Receiving One Dose of TIV
Day 22 (postvaccination) /Day 1 (baseline)

Immunogenicity was assessed in terms of percentages of subjects in both age groups achieving seroconversion or significant increase by SRH area against each of the three vaccine strains, three weeks after receiving one dose of TIV. Seroconversion is defined as percentage of subjects with a pre vaccination SRH area ≤4mm2 achieving a post vaccination SRH area ≥25 mm2. Significant increase is defined as percentage of subjects with a pre-vaccination SRH area \>4mm2 achieving at least 50% increase in post vaccination SRH area. The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is \>40% for adults aged 18 to ≤60 years and \>30% for subjects aged ≥61 years.

Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination Geometric Mean Areas (GMAs), After One Dose of TIV
Day 22 (postvaccination) / Day 1 (baseline)

The antibody responses were evaluated in terms of GMRs of post vaccination GMAs to pre vaccination GMAs against each of the three vaccine strains, three weeks after receiving one dose of TIV. The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is \>2.5 for adults aged 18 to ≤60 years and \> 2.0 in for subjects aged ≥61 years.

Percentages of Subjects With Haemagglutination Inhibition (HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of TIV
Day 1 (baseline) and Day 22 (postvaccination)

Immunogenicity was assessed in terms of percentages of subjects in both age groups with HI titers ≥40, against each of the three vaccine strains, three weeks after receiving one dose of TIV. The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving HI titers ≥ 40 is \>70% for adults aged 18 to ≤60 years and \>60% for subjects aged ≥61 years.

Percentages of Subjects With Seroconversion or Significant Increase in HI Antibody Titers After Receiving One Dose of TIV
Day 22 (postvaccination) / Day 1 (baseline)

Immunogenicity was assessed in terms of percentages of subjects in both age groups achieving seroconversion or significant increase in HI antibody titers after receiving one dose of TIV. Seroconversion is defined as percentage of subjects with a pre vaccination HI titer \<10 to a post vaccination titer ≥40. Significant increase is defined as percentage of subjects with a pre vaccination HI titer ≥10 to at least a 4-fold increase in post vaccination HI antibody titers. The related European (CHMP) criterion for the assessment of immunogenicity is met if \>40% for adults aged 18 to ≤60 years and \>30% for subjects aged ≥61 years achieve seroconversion or significant increase in post-vaccination HI titers.

Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination HI Antibody Titers, After Receiving One Dose of TIV
Day 22 (postvaccination)/ Day 1 (baseline)

The antibody responses following one dose of TIV were evaluated in terms of GMRs of post vaccination against pre vaccination geometric mean HI titers against each of the three vaccine strains, three weeks after receiving one dose of TIV. The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is \>2.5 for adults aged 18 to ≤60 years and \> 2.0 for subjects aged ≥61 years.

Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIV
Day 1 to Day 4 post vaccination

The number of adult and elderly subjects reporting solicited local and systemic adverse events and other solicited adverse events after receiving one dose of TIV are reported.

Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIV
Day 1 through Day 22 post vaccination

The number of subjects in both age groups reporting any unsolicited AEs (between Day 1 to 4), serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal (Day 1 to Day 22), after receiving one dose of TIV is reported.

Secondary Endpoints

Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine.
Day 22 for non-naive/Day 50 for naive subjects
Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine
Day 22 for non-naive/Day 50 for naive
Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine.
Day 1, Day 29, and Day 50
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposePREVENTION

Treatment Arms

ArmTypeDescription
TIV (3-8 years)EXPERIMENTALNon-Naive subjects received one dose and naive subjects received two doses, administered 4 weeks apart, of investigational trivalent influenza vaccine (TIV)
Control TIV (3-8 years)ACTIVE_COMPARATORNon-Naive subjects received one dose and Naive subjects received two doses, administered 4 weeks apart, of control vaccine. Subjects aged 3 to \<4 years and subjects aged 4 to 8 years received different control TIV.
TIV ( 9-17 years)EXPERIMENTALAll subjects received one dose of investigational TIV. The subjects in this cohort were included only for safety analysis.
Control TIV ( (9-17 years)ACTIVE_COMPARATORAll subjects received one dose of the control vaccine. The subjects from this cohort were included only for safety analysis.
TIV (18 to ≤ 60 years)EXPERIMENTALAdult subjects 18 to ≤60 years received one dose of a trivalent, surface antigen inactivated subunit influenza virus vaccine (TIV) formulation 2013/2014 Northern Hemisphere
TIV (≥ 61 years)EXPERIMENTALAdult subjects ≥61 years received one dose of a trivalent, surface antigen inactivated subunit influenza virus vaccine (TIV) formulation 2013/2014 Northern Hemisphere

Interventions

NameTypeDescription
TIVBIOLOGICALInvestigational egg-derived trivalent subunit influenza vaccine.
TIVfBIOLOGICALUS licensed trivalent inactivated subunit influenza vaccine -Fluvirin (Novartis Vaccines and Diagnostics) is approved for use in subjects ≥4 years.
Comparator TIVBIOLOGICALUS licensed trivalent subunit inactivated influenza vaccine- Fluzone (Sanofi Pasteur) is approved for use in children \<4 years.
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Eligibility Criteria

Age Range3 Years to 17 Years
SexALL
Healthy VolunteersYes
Study Sites13

Inclusion Criteria: * Males and females aged 3 to 17 years, in good health as determined by medical history, physical examination and clinical judgment of the investigator * Documented consent provided by parents or legal guardians * For individuals 8 years of age and older, informed assent to part...

Countries:ColombiaMexicoPanamaPhilippinesBelgium
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Frequently asked questions about TIV

What is TIV used for?

TIV is an investigational trivalent subunit inactivated influenza vaccine being developed for the prevention of seasonal influenza and human influenza. It is designed to be administered to healthy children, adolescents, and adults to generate an immune response against circulating influenza virus strains.

Who makes TIV?

TIV is being developed by Novartis AG, which trades under the ticker NVS. The company has conducted clinical trials evaluating the vaccine's safety and immunogenicity in different age groups and geographic regions.

What phase is TIV in?

TIV has completed Phase 2 and Phase 3 clinical trials. The Phase 2 trial was completed in healthy adults aged 18 years and above, and the Phase 3 trial was completed in healthy children and adolescents aged 3 to 17 years. The vaccine remains investigational.

What clinical trials is TIV in?

TIV has been evaluated in two completed trials. NCT01209780 was a Phase 3 study in 3,116 healthy children and adolescents aged 3 to 17 years across Colombia, Mexico, Panama, and the Philippines. NCT01879553 was a Phase 2 study in 126 healthy adults aged 18 years and above in Belgium.

Is TIV the same as a trivalent flu vaccine?

Yes, TIV stands for trivalent inactivated vaccine, meaning it contains three influenza virus strains. It is a subunit vaccine, which includes only parts of the virus to stimulate immunity. The trials evaluated seasonal formulations for different years.