Seasonal Trivalent Inactivated Split Virion Influenza Vac... | NCT03095599

NCT03095599

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
CVIA 051	Other Identifier	PATH

Status Module

Name	Class
Pasteur Institute, Ho Chi Minh City	OTHER_GOV
PATH	OTHER
Quintiles, Inc.	INDUSTRY
World Health Organization

Description Module

Detailed Description

Seasonal influenza viruses circulate widely and cause disease in humans every year. Seasonal influenza viruses evolve continuously, which means that people can get infected multiple times throughout their lives. Therefore the components of seasonal influenza vaccines are reviewed frequently (currently biannually) and updated periodically to ensure continued effectiveness of the vaccines. The World Health Organization (WHO) recommended that influenza vaccines for use in the 2016-2017 northern hemisphere influenza season contain the following viruses:

NYMC BX-35 reassortant of B/Brisbane/60/2008 (B)
NYMC X-179A reassortant of A/California/7/2009 (H1N1)
NYMC X-263B reassortant of H3/A/Hong Kong/4801/2014 (H3N2)

Among circulating influenza B viruses, there were 2 distinct lineages. The B/Brisbane/60/2008-like viruses were from the influenza B/Victoria lineage and represented the predominant circulating influenza B virus. The preclinical evaluation was conducted with all 3 lots of seasonal vaccine used in the Phase 1 study.The Phase 1 study of the IVACFLU-S that was completed in March 2016 identified no safety concerns and demonstrated the vaccine to be highly immunogenic. Given the promising findings, the current study proposed to expand on the safety data of the vaccine, to confirm the immunological findings, and by including individuals up to age 60 to seek regulatory approval for indication in nonelderly adults based on the Vietnam MOH Guidance on Clinical Trial of Influenza Vaccine serological criteria for assessing seasonal influenza.

Phase 2 was conducted at 1 site (District Health Center of Ben Luc, Long An, Vietnam). Subjects were from two age groups: 18-45 years and 46-60 years. Vaccine safety was determined by the Protocol Safety Review Team (PSRT) and approved by Vietnam Ministry of Health (MOH) before starting Phase 3.

Phase 3 was conducted at 2 sites: District Health Center (DHC) of Ben Luc, Long An, Vietnam; and DHC of Long Thanh, Dong Nai. Subjects were from two age groups: 18-45 years and 46-60 years. Both safety and immunogenicity were assessed.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Vaccine	Experimental	Received one dose of IVACFLU-S vaccine intramuscularly.	Biological: IVACFLU-S
Placebo	Placebo Comparator	Received one dose of placebo intramuscularly.	Other: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
IVACFLU-S	Biological	IVACFLU-S is seasonal inactivated, split virion, trivalent influenza vaccine (A/H3N2, A/H1N1, and B), produced in GCP facility by IVAC uses embryonated chicken eggs. This vaccine is purified by sucrose gradient ultracentrifugation (Alfa Wassermann, West Caldwell, NJ), and inactivated with formaldehyde. Each 0.5 mL dose of vaccine contains NYMC X-179A (A/California/7/2009) (H1N1) - 15μg hemagglutinin (HA) NYMC X-263B (A/HongKong/4801/2014) (H3N2) - 15μg HA NYMC BX-35 (B/Brisbane/60/2008) (B) - 15μg HA

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number and Percentage of Subjects Experiencing Solicited Local Adverse Events (AE)	Solicited local AEs were assessed by study staff 30 minutes after vaccination.	Within 30 minutes of vaccination
Number and Percentage of Subjects Experiencing Solicited Systemic Adverse Events (AE)	Solicited systemic AEs were assessed by study staff 30 minutes after vaccination.	Within 30 minutes of vaccination
Number and Percentage of Subjects Experiencing Solicited Local Adverse Events (AE), by Severity	Solicited local AEs were assessed by study staff 30 minutes after vaccination then daily for 7 days by the subjects. Subjects were provided a thermometer, ruler and a diary to record the presence or absence of solicited AEs, severity of the solicited AE and use of concomitant medication. AEs were graded as follows: Mild: Mild symptoms causing no or minimal interference with usual social and functional activities with intervention not indicated. Moderate: Moderate symptoms causing greater than minimal interference with usual social and functional activities with intervention indicated. Severe: Severe symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated. Life-threatening: Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death.	Day 1 to Day 7
Number and Percentage of Subjects Experiencing Solicited Systemic Adverse Events (AE), by Severity	Solicited systemic AEs were assessed by study staff 30 minutes after vaccination then daily for 7 days by the subjects. Subjects were provided a thermometer, ruler and a diary to record the presence or absence of solicited AEs, severity of the solicited AE and use of concomitant medication. AEs were graded as follows: Mild: Mild symptoms causing no or minimal interference with usual social and functional activities with intervention not indicated. Moderate: Moderate symptoms causing greater than minimal interference with usual social and functional activities with intervention indicated. Severe: Severe symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated. Life-threatening: Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death.

Secondary Outcomes

Measure	Description	Time Frame
Number and Percentage of Subjects With at Least a 4-fold Increase in HAI Antibody Titer, by Strain, Age Group, and Baseline Titer	Serum specimens during Phase 3 were tested for the presence and titer of HAI antibodies to each one of the influenza strains represented in the vaccine (A/H1N1, B, and A/H3N2). This testing was performed by VisMederi SRL laboratory (Siena, Italy), by using a validated assay. Sample collection on Day 1 was prior to administration of study product.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Aged 18 through 60 years on the day of screening/enrollment.
Literate (by self-report) and willing to provide written informed consent.
Able to attend all scheduled visits and to comply with all study procedures.
Healthy or medically stable, as established by medical history and physical examination. For individuals with medical conditions, symptoms/signs, if present must be stable under controlled or unchanged for the past 3 months. If medication is used to treat the condition, the medication dose must have been stable for at least 1 month preceding vaccination.

For female subjects:

Not breastfeeding or pregnant (based on negative urine pregnancy test) or plan to become pregnant up to Day 22. Women who are not surgically sterile (hysterectomy or tubal ligation) or post-menopausal for more than 1 year must have negative pregnancy test and, be willing to utilize reliable birth control measures (intrauterine device, hormonal contraception, condom or diaphragm with spermicide) through the Day 22 visit.

Exclusion criteria:

Current or recent (within 2 weeks of enrollment) acute severe illness with or without fever.
Participation in another clinical study involving any therapy within the previous 3 months or planned enrollment in such a study during the period of this study.
Receipt of any non-study vaccine within 4 weeks prior to enrollment or refusal to postpone receipt of such vaccines until after the Day 22 visit.
Received seasonal influenza vaccine in last 6 months
Receipt of immune globulin or other blood products within 3 months prior to study enrollment or planned receipt of such products prior to the Day 22 visit.
Known or suspected congenital or acquired immunodeficiency.
Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within 6 months prior to study enrollment. (For corticosteroids, this means prednisone or equivalent, ≥ 0.5 mg/kg/day; topical steroids are allowed).
Unstable illness by history or physical examination that in the opinion of the Investigator, might interfere with the conduct or results of the study or pose additional risk to the subject.
Hypersensitivity after previous administration of any vaccine.
Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein, and rubber (from the vaccine vial stoppers).
Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion.
Known active tuberculosis or symptoms of active tuberculosis, regardless of cause (self-report).
Current alcohol or drug addiction that in the opinion of the Investigator, might interfere with the ability to comply with study procedures.
History of Guillain-Barré Syndrome
Neoplastic disease or any hematologic malignancy.
Any condition that, in the opinion of the Investigator, would increase the health risk to the subject if he/she participates in the study, or would interfere with the evaluation of the study objectives.

Name	Affiliation	Role
Phan Cong Hung, MD	Pasteur Institute, Ho Chi Minh City	Principal Investigator

PubMed Identifier	Type	Citation	Retractions
31070986	Derived	Lan PT, Toan NT, Thang HA, Thang TC, Be LV, Thai DH, Huong VM, Nga NT, Tang Y, Holt R, Francesco BS, Flores J, Tewari T. A phase 2/3 double-blind, randomized, placebo-controlled study to evaluate the safety and immunogenicity of a seasonal trivalent inactivated split-virion influenza vaccine (IVACFLU-S) in healthy adults in Vietnam. Hum Vaccin Immunother. 2019;15(12):2933-2939. doi: 10.1080/21645515.2019.1613127. Epub 2019 Jun 20.

ID	Title	Description
FG000	Vaccine	IVACFLU-S: Trivalent inactivated split virion influenza vaccine
FG001	Placebo	PBS with pH 7.2; 0.5 ml/per dose

ID	Title	Description
BG000	Vaccine	IVACFLU-S: Trivalent inactivated split virion influenza vaccine
BG001	Placebo	PBS with pH 7.2; 0.5 ml/per dose

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number and Percentage of Subjects Experiencing Solicited Local Adverse Events (AE)

Solicited local AEs were assessed by study staff 30 minutes after vaccination.

All recipients of the vaccine in Phases 2 and 3

Posted

Count of Participants

Participants

Within 30 minutes of vaccination

ID	Title	Description
OG000	Vaccine	Received one dose of IVACFLU-S vaccine intramuscularly.
OG001	Placebo	Received one dose of placebo intramuscularly.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Vaccine	IVACFLU-S: Trivalent inactivated split virion influenza vaccine	0

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Soft tissue injury	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment

ID	Term
D012141	Respiratory Tract Infections
D007239	Infections
D009976	Orthomyxoviridae Infections
D012327	RNA Virus Infections