Safety and Immunogenicity of Different Dosages of High-Dose Quadrivalent Influenza Vaccine in Children 6 Months to 17 Years of Age
- Conditions
- Influenza
- Interventions
- Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 30 μg (split-virion, inactivated)Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 45 μg, (split-virion, inactivated)Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated)Biological: Fluarix Quadrivalent Influenza vaccine (Unadjuvanted QIV-SD) (Inactivated)Biological: FLUAD Pediatric (adjuvanted TIV) (Surface Antigen, Inactivated)
- Registration Number
- NCT03698279
- Lead Sponsor
- Sanofi Pasteur, a Sanofi Company
- Brief Summary
The objectives of this study were:
* To describe the safety of each dosage of high-dose quadrivalent influenza vaccine (QIV-HD) used in the study during the 28 days following each vaccination, and serious adverse events (including adverse events of special interest throughout the study).
* To describe the antibody response induced by each dosage of QIV-HD used in the study compared with unadjuvanted standard-dose quadrivalent influenza vaccine (QIV-SD) by hemagglutination inhibition (HAI) measurement method.
* To describe the antibody response induced by each dosage of QIV-HD used in the study compared with unadjuvanted QIV-SD by virus seroneutralization (SN) measurement method.
* To describe the antibody response induced by the highest acceptable dosage of QIV-HD compared with adjuvanted trivalent influenza vaccine (TIV) by HAI and virus SN measurement methods.
- Detailed Description
Study duration per participant was approximately 180 days for participants who received one dose of vaccine and 208 days for participants who received two doses of vaccine.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 665
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Group 1: QIV-HD 30 μg (US: 6 months to 17 years) High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 30 μg (split-virion, inactivated) Participants from United States (US) (aged 6 months to 17 years) received single injection of 30 microgram (μg) QIV-HD, intramuscularly (IM) at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. Group 2: QIV-HD 45 μg (US: 6 months to 17 years) High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 45 μg, (split-virion, inactivated) Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. Group 3: QIV-HD, 60 μg (US: 6 months to 17 years) High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated) Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. Group 4: Pooled QIV-SD, 15 μg (US: 6 months to 17 years) Fluarix Quadrivalent Influenza vaccine (Unadjuvanted QIV-SD) (Inactivated) Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. Group 5: QIV-HD, 60 μg (Canada: 6 to <24 months) High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated) Participants from Canada (aged 6 to less than \[\<\] 24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28. Group 6: Adjuvanted TIV (Canada: 6 to <24 months) FLUAD Pediatric (adjuvanted TIV) (Surface Antigen, Inactivated) Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
- Primary Outcome Measures
Name Time Method Number of Participants With Unsolicited Adverse Events After Any Vaccination Within 28 days after any vaccination An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. Adverse reactions (ARs) were AEs related to vaccination. An injection site reaction was an AR at and around the injection site. Systemic AEs were all AEs that were not injection or administration site reactions.
Number of Participants With Immediate Unsolicited Adverse Events (AEs) After Any Vaccination Within 30 minutes after any vaccination An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs includes both serious (SAEs) and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. All participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB.
Number of Participants With Neutralization Antibody Titers >= 40 (1/Dilution) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine Day 28 post any vaccination GMT was measured for each influenza strain using HAI assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage.
Number of Participants With Serious Adverse Events (SAEs) After Any Vaccination From Day 0 up to 6 months (i.e. 180 days) post last vaccination An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An SAE which caused death of the participant was considered as fatal SAE. Adverse events of special interest (AESIs) were defined as SAEs which included new onset of Guillain-Barré syndrome, encephalitis/myelitis (including transverse myelitis), Bell's palsy, convulsions, optic neuritis, and brachial neuritis.
Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine Day 0 (pre-vaccination), Day 28 (post any vaccination) GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. GMTRs were calculated as the ratio of GMTs post-vaccination and pre-vaccination.
Number of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine Day 28 post any vaccination Anti-influenza antibodies were measured by hemagglutination inhibition (HAI) assay for strains A/H1N1, A/H3N2, B/Victoria and B/Yamagata lineage. Seroconversion: defined as either HAI titer \<10(1/dilution) at Day 0 and post-vaccination titer greater than or equal to (\>=)40(1/dilution) at Day 28, or HAI titer \>=10(1/dilution) at Day 0 and \>=4-fold increase in HAI titer (1/dilution) at Day 28. Data for this Outcome Measure (OM) was planned to be collected and reported for dose level (QIV-HD 30μg and 45μg) matched separate groups for QIV-SD (Groups 4a, 4b and 4c), instead of pooled QIV-SD arm. Due to complex study design and analysis of doses and age groups, QIV-SD group participants, who matched to participants in QIV-HD 30μg and 45μg dose formulations groups (who were 9 through 17 years old and shared matching age group with QIV-SD control group), included in Groups 4a, 4b and 4c in this OM might be counted in more than once in QIV-SD arms for different dose levels, as applicable.
Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine Day 28 post any vaccination GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. Data for this OM was planned to be collected and reported for dose level (QIV-HD 30 μg and QIV-HD 45 μg) matched separate groups for QIV-SD (Groups 4a, 4b and 4c), instead of pooled QIV-SD arm. Due to the complex study design and analysis of the dose formulation and age groups in the study, QIV-SD group participants, who matched to participants in the QIV-HD 30 μg and QIV-HD 45 μg dose formulations groups (who were 9 through 17 years old and shared a matching age group with QIV-SD control group), included in Groups 4a, 4b and 4c in this OM might be counted in more than once in QIV-SD arms for different dose levels, as applicable.
Geometric Mean Titers Ratio of Influenza Antibodies (Measured by Seroneutralization Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine Day 0 (pre-vaccination), Day 28 (post any vaccination) GMTRs of anti-influenza antibodies were measured using SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage and B/Yamagata lineage. GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination.
Number of Participants With Neutralization Antibody Titers Above Pre-Defined Thresholds Day 28 post any vaccination Neutralizing Antibody titer was measured for each influenza strain with SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage at pre-defined thresholds of \>=20, \>=40 and \>=80 (1/dilution).
Number of Participants With Solicited Systemic Reactions After Any Vaccination: Participants Aged >36 Months Within 7 days after any vaccination A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited systemic reactions included: headache, malaise, myalgia and shivering.
Geometric Mean Titers of Influenza Antibodies (Measured by Seroneutralization [SN] Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine Day 28 post any vaccination GMT was measured for each influenza strain using SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage.
Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer Day 28 post any vaccination Neutralizing Antibody titer was measured for each influenza strain with SN method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage. 2-fold and 4-fold rise was defined as the computed value = post-vaccination computed value / pre-vaccination computed value.
Number of Participants With Solicited Systemic Reactions After Any Vaccination Within 7 days after any vaccination A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited systemic reactions included fever, vomiting, crying abnormal, drowsiness, appetite loss and irritability. Fever was planned to be evaluated for the whole population where as, the other events (vomiting, crying abnormal, drowsiness, appetite lost, and irritability) were planned to be evaluated only in the participants aged 6 months to \<36 months.
Number of Participants With Solicited Injection Site Reactions Within 7 days after any vaccination A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited injection site reactions included tenderness/pain, erythema, swelling, induration and bruising.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (16)
Investigational Site Number 8400001
🇺🇸Miami, Florida, United States
Investigational Site Number 8400002
🇺🇸Atlanta, Georgia, United States
Investigational Site Number 8400015
🇺🇸Newton, Kansas, United States
Investigational Site Number 8400011
🇺🇸Warwick, Rhode Island, United States
Investigational Site Number 1241003
🇨🇦Montreal, Canada
Investigational Site Number 8400014
🇺🇸West Jordan, Utah, United States
Investigational Site Number 1241002
🇨🇦Pierrefonds, Canada
Investigational Site Number 1241001
🇨🇦Quebec, Canada
Investigational Site Number 8400013
🇺🇸El Dorado, Kansas, United States
Investigational Site Number 8400009
🇺🇸Wichita, Kansas, United States
Investigational Site Number 8400004
🇺🇸San Diego, California, United States
Investigational Site Number 8400010
🇺🇸Las Vegas, Nevada, United States
Investigational Site Number 8400005
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 8400003
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 8400012
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 8400007
🇺🇸Metairie, Louisiana, United States