Study on a High-Dose Quadrivalent Influenza Vaccine Compared With Standard-Dose Quadrivalent Influenza Vaccine in Children 6 Months Through 35 Months of Age

NCT04544267 | Terminated Phase 3 Results FDA Drug

• 3 other identifiers: QHD00014U1111-1243-59932019-004721-24
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 10

Brief Summary

The primary objective of the study was to compare the clinical efficacy of high-dose quadrivalent influenza vaccine (QIV-HD) to standard-dose quadrivalent influenza vaccine (QIV-SD) in participants 6 months through 35 months of age for the prevention of laboratory-confirmed influenza illness caused by any influenza A or B type. The secondary objectives of the study were:

• To compare QIV-HD to QIV-SD:
• in participants 6 months through 35 months of age for the prevention of laboratory-confirmed influenza illness caused by any influenza A or B type using a more stringent threshold
• in participants 6 months through 35 months of age for the prevention of laboratory-confirmed protocol-defined influenza-like illness caused by viral strains similar to those contained in the vaccine.
• in participants 6 months through 23 months of age for the prevention of laboratory-confirmed influenza illness caused by any influenza A or B types.
• To compare hemagglutination inhibition (HAI) immune response of QIV-HD to QIV-SD in participants 6 months through 35 months of age
• To describe the HAI, seroneutralization (SN), and anti-neuraminidase (NA) immune response
• To describe the immune response to revaccination in Season 3 (Northern Hemisphere)
• To describe the safety profile of each vaccine

Conditions

Influenza

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Laboratory-Confirmed Influenza Illness Caused by Any Influenza Viral Types/Subtypes

  Laboratory-confirmed influenza was a positive influenza result on either polymerase chain reaction (PCR) or viral culture. An influenza-like illness (ILI) was occurrence of fever concurrently with at least 1 of the following symptoms: cough, wheezing, difficulty breathing, nasal congestion, rhinorrhea, pharyngitis (sore throat), otitis, vomiting, diarrhea, shivering (chills), fatigue (tiredness), headache, or myalgia (muscle aches).

  From 14 days after the first vaccine administration up to 6 months after the last vaccine administration (vaccines administered at Days 0 and 28), approximately 196 days

Secondary Outcomes (34)

• Number of Participants With Influenza-Like Illness Laboratory-Confirmed as Positive for Viral Strains Similar to Those Contained in the Vaccine

  From 14 days after the first vaccine administration up to 6 months after the last vaccine administration (vaccines administered at Days 0 and 28), approximately 196 days

• Number of Participants With Influenza-Like Illness Laboratory-Confirmed as Positive in Participants Aged 6 Through 23 Months for Any Influenza A or B Type

  From 14 days after the first vaccine administration up to 6 months after the last vaccine administration (vaccines administered at Days 0 and 28), approximately 196 days

• Number of Participants With Influenza-Like Illness Laboratory-Confirmed as Positive for Any Influenza A or B Type According to Previous Vaccination Status

  From 14 days after the first vaccine administration up to 6 months after the last vaccine administration (vaccines administered at Days 0 and 28), approximately 196 days

• Number of Participants With Influenza-Like Illness Laboratory-Confirmed as Positive for Viral Strains Similar to Those Contained in the Vaccine According to Previous Vaccination Status

  From 14 days after the first vaccine administration up to 6 months after the last vaccine administration (vaccines administered at Days 0 and 28), approximately 196 days

• Number of Participants With Influenza-Like Illness Laboratory-Confirmed as Positive for Any Influenza A or B Type and Associated With Acute Otitis Media (AOM)

  From 14 days after the first vaccine administration up to 6 months after the last vaccine administration (vaccines administered at Days 0 and 28), approximately 196 days

Study Arms (2)

QIV-HD

EXPERIMENTAL

One injection of QIV-HD on Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.

Biological: Quadrivalent influenza vaccine, high-dose

QIV-SD

ACTIVE COMPARATOR

One injection of QIV-SD on Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.

Biological: Quadrivalent influenza vaccine, standard dose

Interventions

Quadrivalent influenza vaccine, high-dose BIOLOGICAL

Pharmaceutical form: suspension for injection in a pre-filled syringe; route of administration: intramuscular

QIV-HD

Quadrivalent influenza vaccine, standard dose BIOLOGICAL

Pharmaceutical form: suspension for injection in a pre-filled syringe; route of administration: intramuscular

QIV-SD

Eligibility Criteria

• Age: 6 Months - 35 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Aged 6 to 35 months on the day of the first study visit
• 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 who were able to attend all scheduled visits and to comply with all study procedures.
• Covered by health insurance if required by local regulations
• For Season 3 Re-vaccination Cohort: eligible participants must have been enrolled in the Season 1 (2021-2022 Northern Hemisphere season) immunogenicity subset and must have completed all study procedures (ie, blood draws and vaccinations) in Season 1.

You may not qualify if:

• 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.
• For all participants: Receipt of any vaccine in the 30 days preceding the first study vaccination. For participants in immunogenicity subset: Planned receipt of any vaccine before Visit 2 for participants receiving 1 dose of influenza vaccine or Visit 3 for participants receiving 2 doses of influenza vaccine.
• Previous vaccination against influenza in the preceding 6 months with either the study vaccine or another influenza vaccine
• Receipt of immune globulins, blood or blood-derived products in the past 3 months.
• Known or suspected congenital or acquired immunodeficiency (eg, HIV); 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. Exception: participants with an egg allergy are allowed to enroll in the study.
• Thrombocytopenia, bleeding disorder, or receipt of anticoagulants that based on Investigator's judgment contraindicate intramuscular vaccination
• 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 C \[≥ 100.4 F\]). A prospective participant would not be included in the study until the condition was resolved or the febrile event was subsided.
• Identified as natural or adopted child of the Investigator or employee with direct involvement in the proposed study.
• Personal or family history of Guillain-Barre 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.
• For Season 3 (2022-2023 Northern Hemisphere) main cohort: participants who were enrolled in a previous study season are excluded from Season 3, with the exception of the Re-vaccination Cohort.
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (10)

California Research Foundation Site Number : 8400008

San Diego, California, 92123-1881, United States

Location

Acevedo Clinical Research Associates Site Number : 8400007

Miami, Florida, 33142, United States

Location

Emory Childrens Center- Site Number : 8400001

Atlanta, Georgia, 30322, United States

Location

Heartland El Dorado- Site Number : 8400032

El Dorado, Kansas, 67042, United States

Location

Kentucky Pediatrics / Adult Research- Site Number : 8400005

Bardstown, Kentucky, 40004, United States

Location

Velocity Clinical Research- New Orleans Site Number : 8400009

New Orleans, Louisiana, 70119, United States

Location

Ohio Pediatric Research- Site Number : 8400027

Dayton, Ohio, 45414, United States

Location

Rainbow Pediatrics- Site Number : 8400033

Barnwell, South Carolina, 29812, United States

Location

Cenexel JBR- Site Number : 8400006

Salt Lake City, Utah, 84107, United States

Location

Foothill Family Clinic South- Site Number : 8400045

Salt Lake City, Utah, 84121, United States

Location

Related Links

• QHD00014 Plain Language Results Summary

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Limitations and Caveats

The main efficacy cohort was not conducted due to shift in the global influenza vaccine guidelines. Hence, no analysis was performed.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi Pasteur, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A total of 100 participants were in an uncontrolled, open-label sentinel cohort, while all other participants were in an randomized, modified double-blind design. The following measures ensured the integrity of the blinded data for the participants in the randomized, modified double-blind cohort: * The unblinded qualified study staff member, independent of the safety evaluation and other study evaluations, administered the vaccine * The Investigators (or delegates) in charge of safety assessment, the study staff who collect the safety data, and the laboratory personnel who analyze the blood samples did not know which product was administered * The participant / parent / guardian did not know which product was administered. To maintain the blinding of the participant / parent / guardian, the vaccine syringe label was covered with appropriate materials prior to administration.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A sentinel safety cohort was selected for collection safety events where QIV-HD was administered open-label in 100 participants. These subjects did not provide blood samples and were not followed for influenza-like illness (ILI) surveillance. A re-vaccination cohort was composed of a subset of approximately 120 participants from Season 1 (2021-2022 Northern Hemisphere) were re-enrolled and re-randomized in Season 3. The re-vaccination cohort was included, re-randomized to receive either QIV-HD or QIV-SD, provided blood samples in Season 1 and Season 3, and were not followed for ILI surveillance during their participation in Season 3.

Study Record Dates

• First Submitted: September 3, 2020
• First Posted: September 10, 2020
• Study Start: September 15, 2020
• Primary Completion: June 2, 2021
• Study Completion: June 2, 2021
• Last Updated: December 24, 2025
• Results First Posted: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (10)