Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Healthy Adults

Browse trials for

• Influenza, Human 2,214
• Influenza in Birds 113

Keywords

• Influenza, Pandemic, H5N1, Adults

Influenza, Human

2,214 studies on the registry are indexed under Influenza, Human; 163 are open to participants now.

This study's enrollment of 979 is above the median of 238 across 1,853 interventional studies indexed under Influenza, Human.

Lead sponsor

Novartis Vaccines is the lead sponsor of 161 studies on the registry; none are open to participants now.

Study arms

• Experimental
  aH5N1c-High Dose

  Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.

  Biological: Adjuvanted H5N1 pandemic influenza vaccine

• Experimental
  aH5N1c-Low dose

  Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart.

  Biological: Adjuvanted H5N1 pandemic influenza vaccine

Interventions

• BiologicalAdjuvanted H5N1 pandemic influenza vaccine

  Comparison of two doses of aH5N1c vaccine

Primary outcomes

1. Percentages Of Subjects Achieving Hemagglutinin Inhibition (HI) Titers ≥40 Against A/H5N1 Strain.

   The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion. CBER criterion for the adult population is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.

   Time frame: Three weeks after 2nd vaccination (day 43)

2. Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.

   Immunogenicity was measured in terms of the percentages of subjects achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criterion. Seroconversion is defined as either a) in subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or b) in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion for the adult population is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.

   Time frame: Three weeks after 2nd vaccination (day 43)

3. Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination.

   Safety was assessed using the number of subjects who reported solicited local and systemic AEs following vaccination with either low or high dose of aH5N1c vaccine.

   Time frame: From day 1 through day 7 after any vaccination.

4. Number of Subjects Reporting Unsolicited AEs After Any Vaccination.

   Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine.

   Time frame: Any unsolicited AEs - day 1 through day 22 after any vaccination. SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387

Secondary outcomes

1. Geometric Mean Ratios Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine.

   Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c is reported. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criterion if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is \>2.5 for subjects 18-60 years of age.

   Time frame: Day 1; day 22; day 43 and day 387

2. Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain.

   Immunogenicity was assessed in terms of percentage of subjects achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is \>70%.

   Time frame: Day 1, day 22, day 43 and day 387

3. Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.

   Immunogenicity was assessed in terms of percentages of subjects achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as: a) for subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or b) for subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is \>40%.

   Time frame: Day 22, day 43 and day 387

Baseline characteristics

Publications

• Frey SE, Shakib S, Chanthavanich P, Richmond P, Smith T, Tantawichien T, Kittel C, Jaehnig P, Mojares Z, Verma B, Kanesa-Thasan N, Hohenboken M. Safety and Immunogenicity of MF59-Adjuvanted Cell Culture-Derived A/H5N1 Subunit Influenza Virus Vaccine: Dose-Finding Clinical Trials in Adults and the Elderly. Open Forum Infect Dis. 2019 Mar 1;6(4):ofz107. doi: 10.1093/ofid/ofz107. eCollection 2019 Apr. PubMed 30968056 ↗