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Trial record 1 of 1 for:    NCT03282240
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Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine in Participants ≥65 Years in the US

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ClinicalTrials.gov Identifier: NCT03282240
Recruitment Status : Completed
First Posted : September 13, 2017
Results First Posted : December 17, 2019
Last Update Posted : December 17, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Brief Summary:
This randomized, modified double-blind, active-controlled, multi-center trial assessed the safety and immunogenicity of the high-dose quadrivalent influenza vaccine (QIV-HD) compared to either the licensed or investigational high-dose trivalent influenza vaccine (TIV-HD) in adults.

Condition or disease Intervention/treatment Phase
Influenza Biological: QIV-HD Biological: Licensed TIV-HD1 Biological: Investigational TIV-HD2 Phase 3

Detailed Description:
This randomized, modified double-blind, active-controlled, multi-center trial was conducted in healthy adults (greater than and equal to [>=] 65 years) to assess the safety and immunogenicity (geometric mean titers and seroconversion for the 4 virus strains at 28 days post vaccination) of the QIV-HD compared to one of the TIV-HDs containing either the B strain from the primary lineage (TIV-HD1; licensed vaccine [Fluzone® High-Dose] for the 2017-2018 Northern Hemisphere [NH] influenza season) or the B strain from the alternate lineage (TIV-HD2, investigational TIV-HD containing an alternate B strain).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2670 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: QHD00013 was a phase III, randomized, modified double-blind, active-controlled, multi-center trial.
Masking: Double (Participant, Outcomes Assessor)
Masking Description: QHD00013 was a modified double-blind trial with an unblinded administrator used at each trial site. The administrator was not involved in any of the blinded study assessments (e.g., safety).
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine Administered by Intramuscular Route in Participants Aged 65 Years and Older
Actual Study Start Date : September 8, 2017
Actual Primary Completion Date : November 2, 2017
Actual Study Completion Date : April 19, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: QIV-HD
Participants randomized to receive a single injection of 0.7 mL QIV-HD by intramuscular (IM) route at Day 0.
Biological: QIV-HD
0.7 mL-dose was administered intramuscularly (IM) into the upper arm area.
Other Name: High-dose quadrivalent influenza vaccine

Active Comparator: TIV-HD1 (Licensed TIV-HD1)
Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.
Biological: Licensed TIV-HD1
0.5 mL-dose was administered IM into the upper arm area.
Other Name: High-dose trivalent influenza vaccine

Active Comparator: TIV-HD2 (Investigational TIV-HD2)
Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Biological: Investigational TIV-HD2
0.5 mL-dose was administered IM into the upper arm area.
Other Name: High-dose trivalent influenza vaccine (alternate B strain)




Primary Outcome Measures :
  1. Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [ Time Frame: Day 28 post-vaccination ]
    GMTs of anti-influenza antibodies were measured using an hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). For each A strain, the comparison was made with the pooled TIV-HD groups. For each B strain, the comparison was made with the TIV-HD group containing the corresponding B strain. TIV-HD 1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.

  2. Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [ Time Frame: Day 28 post-vaccination ]
    Anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Seroconversion was defined as either a HAI titer less than (<) 10 (1/dilution) at Day 0 and post-injection 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. For each A strain, the comparison was made with the pooled TIV-HD groups. For each B strain, the comparison was made with the TIV-HD group containing the corresponding B strain. TIV-HD 1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.


Secondary Outcome Measures :
  1. GMTs of B Strains Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [ Time Frame: Day 28 post-vaccination ]
    Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). For each B strain, the immunogenicity of QIV-HD was compared to that of TIV-HD group which contains the corresponding B strain. TIV-HD1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.

  2. GMT Ratios of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
    GMTs of anti-influenza antibodies using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Geometric Mean Titers Ratios (GMTRs) were calculated as the ratio of GMTs post vaccination and pre-vaccination.

  3. Percentage of Participants Achieving Seroconversion Against Antigens of B Strains After Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [ Time Frame: Day 28 post-vaccination ]
    Seroconversion was defined as either a HAI titer <10 (1/dilution) at Day 0 and post-injection titer >=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. Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
    Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). Seroprotection was defined as a HAI titer >=40 (1/dilution) at Day 0 and Day 28.

  5. Geometric Mean Titers of Influenza Antibodies (Seroneutralization [SN] Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
    GMTs of anti-influenza antibodies were measured using SN assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2).

  6. GMTRs of Influenza Antibodies (SN Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
    GMTRs of anti-influenza antibodies were measured using SN assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination.

  7. Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 [ Time Frame: Day 0, Day 28 ]
    Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Neutralizing antibody was defined as titers >=20 (1/dilution), >=40 (1/dilution), >=80 (1/dilution) at Day 0 and Day 28.

  8. Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28 [ Time Frame: Day 28 ]
    Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). 2-fold and 4-fold rise was defined as the computed value = post-vaccination computed value / baseline computed value.

  9. Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28 [ Time Frame: Day 0, Day 28 ]
    Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Detectable neutralization antibody titer >= 1:10 (1/dilution) at Day 0 and Day 28.

  10. Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [ Time Frame: Within 7 days after vaccination ]
    Solicited injection site: Pain, Erythema, Swelling, Induration, and Bruising. Grade 3 reactions: Pain - interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention; Erythema, Swelling, Induration, and Bruising: >100 millimeters (mm). Systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering. Grade 3 reactions: Fever: >=39°C; Headache, Malaise, Myalgia, and Shivering: interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.

  11. Number of Participants With Immediate Adverse Event (AEs) [ Time Frame: Within 30 minutes after vaccination ]
    Participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurring during that time was recorded as immediate unsolicited systemic AEs (AEs that were related to the investigational product) in the case report book (CRB). Unsolicited AE was an observed AE that did 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 was 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, was a congenital anomaly/birth defect, or was an important medical event.

  12. Number of Participant With Unsolicited Adverse Event (AE) [ Time Frame: Within 28 days after vaccination ]
    An unsolicited AE was an observed AE that did 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 was 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, was a congenital anomaly/birth defect, or was an important medical event.

  13. Number of Participant With Serious Adverse Event [ Time Frame: Up to 6 months after vaccination ]
    An serious adverse event was any untoward medical occurrence that at any dose results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity,is a congenital anomaly/birth defect, or was an important medical event.



Information from the National Library of Medicine

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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 had been signed and dated.
  • Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

  • Participation at the time of trial enrollment (or in the 4 weeks preceding the trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
  • Receipt of any vaccine in the 4 weeks (28 days) preceding the trial vaccination or planned receipt of any vaccine prior to Visit 2.
  • Previous vaccination against influenza (in the preceding 6 months) with either the trial 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 any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial 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 trial conduct or completion.
  • Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
  • Identified as an Investigator or employee of the Investigator or trial center with direct involvement in the proposed trial, 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 trial.
  • Personal or family history of Guillain-Barré syndrome.
  • Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that is stable at the time of vaccination in the absence of therapy and participants who have 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 >= 38.0°C [>= 100.4°F]). A prospective participant should not be included in the trial until the condition has resolved or the febrile event had subsided.

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): NCT03282240


Locations
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Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
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] July 20, 2017
Statistical Analysis Plan  [PDF] April 18, 2018

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier: NCT03282240    
Other Study ID Numbers: QHD00013
U1111-1183-5556 ( Other Identifier: World Health Organization Universal Trial Number )
First Posted: September 13, 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. Participant 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.: No
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