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Trial record 1 of 1 for:    QHD00008
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Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine in Patients ≥65 Years

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ClinicalTrials.gov Identifier: NCT03233217
Recruitment Status : Completed
First Posted : July 28, 2017
Results First Posted : December 17, 2019
Last Update Posted : December 17, 2019
Sponsor:
Collaborator:
Sanofi K.K.
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

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).

Condition or disease Intervention/treatment Phase
Influenza Biological: QIV-HD by IM Biological: QIV-SD by SC Biological: QIV-HD by SC Phase 1 Phase 2

Detailed Description:
This phase I/II, randomized, modified double-blind, multi-center study was conducted in 175 healthy Japanese adults aged 65 years and older to describe the safety profile and immune responses (geometric mean titers and seroconversion for the 4 common strains at 28 days post-vaccination) of the QIV-HD administered by intramuscular (IM) and subcutaneous (SC) methods. A local standard-dose Quadrivalent Influenza Vaccine (QIV-SD) administered by SC method served as a control arm.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 175 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

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).

Masking: Double (Participant, Investigator)
Masking Description: 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.
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine Administered by Intramuscular or Subcutaneous Route in Participants Aged 65 Years and Older in Japan
Actual Study Start Date : September 15, 2017
Actual Primary Completion Date : November 28, 2017
Actual Study Completion Date : November 28, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: Cohort 1: QIV-HD by IM
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
IM, injected into the upper arm (deltoid area)
Other Name: High-Dose Influenza Vaccine Quadrivalent (IM)

Experimental: Cohort 1: QIV-HD by SC
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
SC, injection into the upper arm (posterior region)
Other Name: High-Dose Influenza Vaccine Quadrivalent (SC)

Experimental: Cohort 2: QIV-HD by IM
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
IM, injected into the upper arm (deltoid area)
Other Name: High-Dose Influenza Vaccine Quadrivalent (IM)

Experimental: Cohort 2: QIV-HD by SC
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
SC, injection into the upper arm (posterior region)
Other Name: High-Dose Influenza Vaccine Quadrivalent (SC)

Active Comparator: Cohort 2: QIV-SD by SC
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
SC, injected into the upper arm (posterior region)
Other Name: Standard-Dose Influenza Vaccine Quadrivalent




Primary Outcome Measures :
  1. Number of Participants With Immediate Unsolicited Adverse Events (AE) After Vaccination [ Time Frame: Within 30 minutes 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.

  2. Number of Participants With Solicited Injection Site and Systemic Reactions [ Time Frame: Within 7 days after vaccination ]
    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.

  3. Number of Participants With Unsolicited Adverse Events After Vaccination [ Time Frame: Within 28 days 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.

  4. Number of Participant With Serious Adverse Events (SAEs) After Vaccination [ Time Frame: Up to 6 months 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.


Secondary Outcome Measures :
  1. Cohort 2: Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD [ Time Frame: Day 0 (pre-vaccination) and Day 28 (post-vaccination) ]
    GMT of anti-influenza antibodies strains (A1, A1-like, A2, A2-like, B1, B2, B2-like) were measured using a hemagglutination inhibition (HAI) assay.

  2. Cohort 2: Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD [ Time Frame: Day 0 (pre-vaccination) and Day 28 (post-vaccination) ]
    GMT of anti-influenza antibodies strains (A1, A1-like, A2, A2-like, B1, B2, B2-like) were measured using an HAI assay. GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination.

  3. Cohort 2: Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With QIV-HD or QIV-SD [ Time Frame: Day 28 (post-vaccination) ]
    Anti-influenza antibodies were measured by using the HAI assay for the strains A1, A1-like, A2, A2-like, B1, B2, and B2-like. Seroconversion was defined as either a HAI titer lesser than (<) 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 a >=4-fold increase in HAI titer (1/dilution) at Day 28.

  4. Cohort 2: Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With QIV-HD or QIV-SD [ Time Frame: Day 0 (pre-vaccination) and Day 28 (post-vaccination) ]
    Anti-influenza antibodies were measured by using the HAI assay for the strains A1, A1-like, A2, A2-like, B1, B2, and B2-like. Seroprotection was defined as a HAI titer >=40 (1/dilution) at Day 0 and Day 28.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged >= 65 years on the day of inclusion.
  • Informed consent form has been signed and dated.
  • Able to attend all scheduled visits and to comply with all study procedures.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03233217


Locations
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Japan
Sanofi Pasteur Investigational Site
Tokyo, Japan
Sanofi Pasteur Investigational Site
Ōsaka, Japan
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Sanofi K.K.
Investigators
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Study Director: Medical Director Sanofi Pasteur, a Sanofi Company
  Study Documents (Full-Text)

Documents provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):
Study Protocol  [PDF] May 12, 2017
Statistical Analysis Plan  [PDF] September 13, 2017

Additional Information:
Publications:
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Responsible Party: Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier: NCT03233217    
Other Study ID Numbers: QHD00008
U1111-1183-5525 ( Other Identifier: World Health Organization Universal Trial Number )
DFI15130 ( Other Identifier: Sanofi K.K. )
First Posted: July 28, 2017    Key Record Dates
Results First Posted: December 17, 2019
Last Update Posted: December 17, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to participant 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://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):
Influenza
Additional relevant MeSH terms:
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Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs