Seasonal Trivalent Inactivated Split Virion Influenza Vaccine Clinical Trial (IVACFLU-S) - PHASE 2/3
- Conditions
- Influenza, Human
- Interventions
- Other: PlaceboBiological: IVACFLU-S
- Registration Number
- NCT03095599
- Brief Summary
This Phase 2/3 study assessed whether a single dose of seasonal trivalent inactivated split virion influenza vaccine (IVACFLU-S) is safe and well-tolerated in adults 18 to 60 years of age; and whether it will induce immune responses to each of the 3 vaccine antigens to meet 1 or both age group-specific Vietnam Ministry of Health (MOH) licensure requirements.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 889
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Received one dose of placebo intramuscularly. Vaccine IVACFLU-S Received one dose of IVACFLU-S vaccine intramuscularly.
- Primary Outcome Measures
Name Time Method Number and Percentage of Subjects Experiencing Solicited Local Adverse Events (AE) Within 30 minutes of vaccination Solicited local AEs were assessed by study staff 30 minutes after vaccination.
Number and Percentage of Subjects Experiencing Solicited Systemic Adverse Events (AE) Within 30 minutes of vaccination Solicited systemic AEs were assessed by study staff 30 minutes after vaccination.
Number and Percentage of Subjects Experiencing Solicited Local Adverse Events (AE), by Severity Day 1 to Day 7 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.Number and Percentage of Subjects Experiencing Solicited Systemic Adverse Events (AE), by Severity Day 1 to Day 7 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.Number and Percentage of Subjects Experiencing Fever Day 1 to Day 7 Subjects reporting body temperature by maximum severity; Grade 0: \<38°C, Grade 1: 38.0 - \<38.6°C, Grade 2: 38.6 - \<39.3°C, Grade 3: 39.3 - \<40.0°C, Grade 4: \>= 40.0°C
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events (AE) Day 1 to Day 21 Unsolicited AEs were observed by study staff while the subject is at a clinic for a study visit or reported by the subject at any time. Any sign or symptom that would normally be considered a "solicited AE" (for example, fever, nausea, injection site pain) starting after 7 days post-vaccination was to be recorded as an unsolicited AE. The clinician determined whether there was a reasonable possibility that the investigational product(s) caused or contributed to an AE. The following guidelines were used:
* Related: There is a reasonable possibility that the study vaccine caused the AE. "Reasonable possibility" means that there is evidence to suggest a causal relationship between the study product and the AE.
* Not Related: There is not a reasonable possibility that the administration of the study product caused the event.Number and Percentage of Subjects Experiencing Unsolicited Serious Adverse Events (SAE) Day 1 to Day 91 Unsolicited AEs were observed by study staff while the subject is at a clinic for a study visit or reported by the subject at any time. Any sign or symptom that would normally be considered a "solicited AE" (for example, fever, nausea, injection site pain) starting after 7 days post-vaccination was to be recorded as an unsolicited AE. The clinician determined whether there was a reasonable possibility that the investigational product(s) caused or contributed to an AE. The following guidelines were used:
* Related: There is a reasonable possibility that the study vaccine caused the AE. "Reasonable possibility" means that there is evidence to suggest a causal relationship between the study product and the AE.
* Not Related: There is not a reasonable possibility that the administration of the study product caused the event.Number and Percentage of Subjects With Seroconversion of Hemagglutination Inhibition (HAI) Antibodies for Vaccine Antigens, Overall and by Age Group Day 1, Day 22 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.
Seroconversion is defined as a serum HAI antibody titer meeting the following criteria:
* pre-vaccination titer \< 1:10 and a post-vaccination titer measured on Day 22 of ≥ 1:40, or
* pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination measured on Day 22Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibodies for Vaccine Antigens at Baseline and Day 22, Overall and by Age Group Day 1, Day 22 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.
Geometric Mean Fold Change of Serum Hemagglutination Inhibition (HAI) Antibody Titer, Overall and by Age Group Day 1, Day 22 Fold change in titer between Day 1 and Day 22. 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.
- Secondary Outcome Measures
Name Time Method Number and Percentage of Subjects With at Least a 4-fold Increase in HAI Antibody Titer, by Strain, Age Group, and Baseline Titer Day 22 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.
Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibodies for Vaccine Antigens at Baseline and Day 22: All Subjects Day 1, Day 22 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/H1N1). 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.
Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibodies for Vaccine Antigens at Baseline and Day 22: Subjects Aged 18-45 Day 1, Day 22 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.
Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibodies for Vaccine Antigens at Baseline and Day 22: Subjects Aged 46-60 Day 1, Day 22 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.
Geometric Mean Fold Change in HAI Antibody Titer, by Strain, Age Group, and Baseline Titer Day 1, Day 22 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.
Trial Locations
- Locations (1)
Pasteur Institute, Ho Chi Minh City
🇻🇳Ho Chi Minh City, Vietnam