Safety and Immunogenicity of Different Dosages of High-Dose Quadrivalent Influenza Vaccine in Children 6 Months to 17 Years of Age (QHD04)

Sanofi

Status and phase: Completed; Phase 2

Conditions: Influenza

Treatments: Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 30 μg (split-virion, inactivated); Biological: Fluarix Quadrivalent Influenza vaccine (Unadjuvanted QIV-SD) (Inactivated); Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 45 μg, (split-virion, inactivated); Biological: FLUAD Pediatric (adjuvanted TIV) (Surface Antigen, Inactivated); Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03698279

2018-005026-39 (EudraCT Number)

QHD04

U1111-1189-3713 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 665 patients

Sex: All

Ages: 6 months to 17 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Aged 6 months to 17 years on the day of inclusion.
• Assent form was signed and dated by the participant (7 to 17 years of age) and informed consent form was signed and dated by the parent(s) or guardian(s) and by an independent witness, if required by local regulations.
• Participant and parent/guardian were able to attend all scheduled visits and complied with all study procedures.
• For participants aged <24 months: Born at full term of pregnancy (greater than or equal to [>=] 37 weeks) and/or with a birth weight >=2.5 kilogram.

Exclusion criteria:

• Participant was pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche.
• Participation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.
• Receipt of any vaccine in the 30 days preceding the first study vaccination, or planned receipt of any vaccine before Visit 3 for participants receiving 1 dose of influenza vaccine or Visit 5 for participants receiving 2 doses of influenza vaccine.
• For previously influenza vaccinated participants: Previous vaccination against influenza in the preceding 6 months with either the study vaccine or another vaccine.
• For previously influenza unvaccinated participants: Any influenza vaccination (from birth to the day of inclusion) with either the study vaccine or another influenza vaccine.
• For previously influenza unvaccinated participants: Any previous laboratory confirmed influenza infection (from birth to the day of inclusion)
• Receipt of immune globulins, blood or blood-derived products in the past 3 months.
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances.
• Thrombocytopenia or bleeding disorder, contraindicating IM vaccination based on Investigator's judgement.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Current alcohol abuse or drug addiction.
• Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with study conduct or completion.
• Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature >=38.0°Celsius [>=100.4°Fahrenheit]). A prospective participant should not be included in the study until the condition had resolved or the febrile event had subsided.
• Identified as an immediate family member (i.e., spouse, natural or adopted child, grandchild, nephew, or niece) of the Investigator or employee with direct involvement in the proposed study.
• Personal history of Guillain-Barré syndrome.
• Any condition that in the opinion of the Investigator would pose a health risk to the participant if enrolled or could interfere with the evaluation of the vaccine
• Personal history of clinically significant development delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder.
• Known seropositivity for hepatitis B or hepatitis C.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

---

665 participants in 6 patient groups

Group 1: QIV-HD 30 μg (US: 6 months to 17 years)

Experimental group

Description:

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.

Treatment:

Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 30 μg (split-virion, inactivated)

Group 2: QIV-HD 45 μg (US: 6 months to 17 years)

Experimental group

Description:

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.

Treatment:

Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 45 μg, (split-virion, inactivated)

Group 3: QIV-HD, 60 μg (US: 6 months to 17 years)

Experimental group

Description:

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.

Treatment:

Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated)

Group 4: Pooled QIV-SD, 15 μg (US: 6 months to 17 years)

Active Comparator group

Description:

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.

Treatment:

Biological: Fluarix Quadrivalent Influenza vaccine (Unadjuvanted QIV-SD) (Inactivated)

Group 5: QIV-HD, 60 μg (Canada: 6 to <24 months)

Experimental group

Description:

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.

Treatment:

Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated)

Group 6: Adjuvanted TIV (Canada: 6 to <24 months)

Active Comparator group

Description:

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.

Treatment:

Biological: FLUAD Pediatric (adjuvanted TIV) (Surface Antigen, Inactivated)