Safety and Immunogenicity of Different Dosages of High-Dose Quadrivalent Influenza Vaccine in Children 6 Months to 17 Years of Age

Study at a glance

From the registry record, last updated by the sponsor on 4 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

Safety and Immunogenicity of Different Dosages of High-Dose Quadrivalent Influenza Vaccine in Children 6 Months to 17 Years of Age

ClinicalTrials.gov ID

NCT03698279

Acronym / sponsor ID

QHD04 / QHD04

Conditions

Influenza

Phase

Phase 2

Study type

Interventional

Recruitment status

Completed

Enrolment

665 participants (actual)

Lead sponsor

Sanofi Pasteur, a Sanofi CompanyIndustry (pharma, biotech, devices)

Study start

9 Oct 2018 (actual)

Primary completion

16 Oct 2019 (actual)

Study completion

16 Oct 2019 (actual)

First posted

5 Oct 2018 (actual)

Results

Posted 1 Jun 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Prevention

Allocation

Randomised

Intervention model

Sequential

Masking

Triple blind (participant, investigator, outcomes assessor)

Number of arms

6

Model description

The study was divided into 13 groups and enrolled participants in 4 stages. The study used a stepwise age de-escalation and dose ascension design for children 6 months to less than (<) 5 years of age.

Who may qualify

Ages

6 months to 17 years

Sex

All

Healthy volunteers

Accepted

Age groups

Child

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Immediate Unsolicited Adverse Events (AEs) After Any Vaccination

   Time frame: 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.

2. Number of Participants With Unsolicited Adverse Events After Any Vaccination

   Time frame: 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.

3. Number of Participants With Serious Adverse Events (SAEs) After Any Vaccination

   Time frame: 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.

4. 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

   Time frame: 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.

5. 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

   Time frame: 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.

6. 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

   Time frame: 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.

7. 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

   Time frame: 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.

8. 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

   Time frame: 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.

9. 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

   Time frame: 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.

10. Number of Participants With Neutralization Antibody Titers Above Pre-Defined Thresholds

    Time frame: 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).

11. Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer

    Time frame: 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.

12. Number of Participants With Solicited Injection Site Reactions

    Time frame: 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.

13. Number of Participants With Solicited Systemic Reactions After Any Vaccination

    Time frame: 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.

14. Number of Participants With Solicited Systemic Reactions After Any Vaccination: Participants Aged >36 Months

    Time frame: 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.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2022.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Results publication: PubMed 33610374Chang LJ, Anderson EJ, Jeanfreau R, He Y, Hicks B, Shrestha A, Pandey A, Landolfi V, DeBruijn I; QHD04 Study Group. Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through <18 years of age: A randomized controlled phase II dose-finding trial. Vaccine. 2021 Mar 12;39(11):1572-1582. doi: 10.1016/j.vaccine.2021.02.014. Epub 2021 Feb 18.
• Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

16 sites in 2 countries: see every site and its status.