Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine in Patients ≥65 Years

NCT03233217 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: QHD00008U1111-1183-5525DFI15130
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II, randomized, modified double-blind, multi-center study assessed the safety and immunogenicity of a high-dose Quadrivalent influenza vaccine (QIV-HD) in older adults (greater than or equal to \[\>=\] 65 years).

Conditions

Influenza

Keywords

Influenza

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Immediate Unsolicited Adverse Events (AE) After Vaccination

  An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of symptom and/or onset post-vaccination. Unsolicited AEs includes both serious and non-serious unsolicited AEs. A serious adverse event is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. All participants were observed for 30 minutes after vaccination, and any unsolicited AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB.

  Within 30 minutes after vaccination

• Number of Participants With Solicited Injection Site and Systemic Reactions

  A solicited reaction was an adverse reaction observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited injection site reactions: pain, erythema, swelling, induration, and bruising. Solicited systemic reactions: fever, headache, malaise, myalgia, and shivering.

  Within 7 days after vaccination

• Number of Participants With Unsolicited Adverse Events After Vaccination

  An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRB in terms of symptom and/or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. A serious adverse event is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

  Within 28 days after vaccination

• Number of Participant With Serious Adverse Events (SAEs) After Vaccination

  An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

  Up to 6 months after vaccination

Secondary Outcomes (4)

• Cohort 2: Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD

  Day 0 (pre-vaccination) and Day 28 (post-vaccination)

• Cohort 2: Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD

  Day 0 (pre-vaccination) and Day 28 (post-vaccination)

• Cohort 2: Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With QIV-HD or QIV-SD

  Day 28 (post-vaccination)

• Cohort 2: Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With QIV-HD or QIV-SD

  Day 0 (pre-vaccination) and Day 28 (post-vaccination)

Study Arms (5)

Cohort 1: QIV-HD by IM

EXPERIMENTAL

Participants were randomized to receive a single 0.7-milliliter (mL) injection of QIV-HD by IM route on Day 0.

Biological: QIV-HD by IM

Cohort 1: QIV-HD by SC

EXPERIMENTAL

Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0.

Biological: QIV-HD by SC

Cohort 2: QIV-HD by IM

EXPERIMENTAL

Participants were randomized to receive a single 0.7 mL injection of QIV-HD by IM route on Day 0.

Biological: QIV-HD by IM

Cohort 2: QIV-HD by SC

EXPERIMENTAL

Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0.

Biological: QIV-HD by SC

Cohort 2: QIV-SD by SC

ACTIVE COMPARATOR

Participants were randomized to receive a single 0.5 mL injection of QIV-SD by SC route on Day 0.

Biological: QIV-SD by SC

Interventions

QIV-HD by IM BIOLOGICAL

IM, injected into the upper arm (deltoid area)

Also known as: High-Dose Influenza Vaccine Quadrivalent (IM)

Cohort 1: QIV-HD by IM; Cohort 2: QIV-HD by IM

QIV-SD by SC BIOLOGICAL

SC, injected into the upper arm (posterior region)

Also known as: Standard-Dose Influenza Vaccine Quadrivalent

Cohort 2: QIV-SD by SC

QIV-HD by SC BIOLOGICAL

SC, injection into the upper arm (posterior region)

Also known as: High-Dose Influenza Vaccine Quadrivalent (SC)

Cohort 1: QIV-HD by SC; Cohort 2: QIV-HD by SC

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Informed consent form has been signed and dated.
• Able to attend all scheduled visits and to comply with all study procedures.

You may not qualify if:

• Participation at the time of study enrollment (or in the 4 weeks preceding the 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 vaccination with live vaccines within the past 27 days preceding the study vaccination or any vaccination with inactivated vaccines within the past 6 days preceding the study vaccination, or planned receipt of any vaccine prior to Visit 3.
• Previous vaccination against influenza (in the preceding 6 months) with either the study vaccine or another vaccine.
• 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 eggs, chicken proteins, or any of the vaccine components, or history of a life-threatening reaction to the vaccine 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 judgment.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Alcohol or substance abuse that, in the opinion of the Investigator might interfere with the study conduct or completion.
• Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with study conduct or completion.
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
• Personal or family history of Guillain-Barré syndrome.
• Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that was stable at the time of vaccination in the absence of therapy and participants who had a history of neoplastic disease and have been disease free for \>=5 years).
• Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature \>=37.5°Celsius). A prospective participant were not be included in the study until the condition had resolved or the febrile event had subsided.
• History of convulsions.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead
• Sanofi: collaborator

Study Sites (2)

Sanofi Pasteur Investigational Site

Ōsaka, Japan

Location

Sanofi Pasteur Investigational Site

Tokyo, Japan

Location

Related Publications (1)

• Sanchez L, Matsuoka O, Inoue S, Inoue T, Meng Y, Nakama T, Kato K, Pandey A, Chang LJ. Immunogenicity and safety of high-dose quadrivalent influenza vaccine in Japanese adults >/=65 years of age: a randomized controlled clinical trial. Hum Vaccin Immunother. 2020 Apr 2;16(4):858-866. doi: 10.1080/21645515.2019.1677437. Epub 2019 Nov 19.

  PMID: 31634025 BACKGROUND

Related Links

• Related info

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

Results Point of Contact

• Title: Medical Director
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

800-633-1610

Study Officials

• Medical Director

  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 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: QHD00008 was a modified double-blind study in which only the designated administrator at each study site knew which vaccine was administered to the participants. The participants and the Investigator/Sub-investigator in charge of the safety assessment were blinded in order to decrease the potential bias in safety assessment.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Safety and tolerability was initially assessed in the first 10 participants in a smaller cohort (Cohort 1). Participants were randomized 1:1 into 2 groups in Cohort 1: QIV-HD by IM route (n=5) and QIV-HD by SC route (n=5). After review of the local and systemic adverse events, the remaining 165 participants were enrolled (Cohort 2). Participants were randomized 1:1:1 into 3 groups in Cohort 2: QIV-HD by IM route (n=55), QIV-HD by SC route (n=55), and QIV-SD by SC route (n=55).

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: July 28, 2017
• Study Start: September 15, 2017
• Primary Completion: November 28, 2017
• Study Completion: November 28, 2017
• Last Updated: April 4, 2022
• Results First Posted: December 17, 2019

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

JP (2)