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Influenza, HumanPhase 2/3IVACFLUS-0203NCT03095599

Seasonal Trivalent Inactivated Split Virion Influenza Vaccine Clinical Trial (IVACFLU-S) - PHASE 2/3

A Phase 2/3 study testing IVACFLU-S in people with Influenza, Human, run by Institute of Vaccines and Medical Biologicals, Vietnam at 1 site in Vietnam.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Influenza, Human
What is being tested?
IVACFLU-S
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
889 participants
Where
1 siteVietnam
Study dates
20 Mar 2017to 5 Oct 2017
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Vietnam1 site
  • Pasteur Institute, Ho Chi Minh City

    Ho Chi Minh City

Other trials in Vietnam

About this study

Official title: A Phase 2/3 Double Blinded, Randomized, Placebo-Controlled Study in Healthy Adult Volunteers in Vietnam to Examine the Safety and Immunogenicity of a Seasonal Trivalent Inactivated Split Virion Influenza Vaccine (IVACFLU-S) Produced by IVAC

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.

Read the 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.

Being tested
IVACFLU-S, Placebo
Keywords
Influenza, Vaccine
Medical subject headings
Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IVACFLU-SBiological

    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
  • PlaceboOther

    Phosphate buffered saline with pH 7.2; 0.5 ml/per dose

Study groups in NCT03095599
Study groupRoleWhat they receive
VaccineExperimentalReceived one dose of IVACFLU-S vaccine intramuscularly.
Receives: Biological: IVACFLU-S
PlaceboPlacebo comparatorReceived one dose of placebo intramuscularly.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: Within 30 minutes of vaccination

  2. Number and Percentage of Subjects Experiencing Solicited Systemic Adverse Events (AE)

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

    Measured: Within 30 minutes of vaccination

  3. 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.

    Measured: Day 1 to Day 7

  4. 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.

    Measured: Day 1 to Day 7

  5. Number and Percentage of Subjects Experiencing Fever

    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

    Measured: Day 1 to Day 7

  6. Number and Percentage of Subjects Experiencing Unsolicited Adverse Events (AE)

    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.

    Measured: Day 1 to Day 21

  7. Number and Percentage of Subjects Experiencing Unsolicited Serious Adverse Events (SAE)

    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.

    Measured: Day 1 to Day 91

  8. Number and Percentage of Subjects With Seroconversion of Hemagglutination Inhibition (HAI) Antibodies for Vaccine Antigens, Overall and by Age Group

    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 22

    Measured: Day 1, Day 22

  9. Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibodies for Vaccine Antigens at Baseline and Day 22, Overall and by Age Group

    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.

    Measured: Day 1, Day 22

  10. Geometric Mean Fold Change of Serum Hemagglutination Inhibition (HAI) Antibody Titer, Overall and by Age Group

    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.

    Measured: Day 1, Day 22

Secondary outcomes (5)
  1. 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.

    Measured: Day 22

  2. Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibodies for Vaccine Antigens at Baseline and Day 22: All Subjects

    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.

    Measured: Day 1, Day 22

  3. Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibodies for Vaccine Antigens at Baseline and Day 22: Subjects Aged 18-45

    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.

    Measured: Day 1, Day 22

  4. Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) Antibodies for Vaccine Antigens at Baseline and Day 22: Subjects Aged 46-60

    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.

    Measured: Day 1, Day 22

  5. Geometric Mean Fold Change 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.

    Measured: Day 1, Day 22

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2017
  2. Study start20 Mar 2017
  3. Primary completion5 Oct 2017
  4. Study completion5 Oct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
889 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03095599
Sponsor's protocol ID
IVACFLU-S 0203
Other IDs
CVIA 051
Acronym
IVACFLUS-0203
Status last verified
May 2019
First submitted
13 Mar 2017
Last updated
22 Jul 2019
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 31070986

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing IVACFLU-S in people with Influenza, Human, run by Institute of Vaccines and Medical Biologicals, Vietnam at 1 site in Vietnam.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number and Percentage of Subjects Experiencing Solicited Local Adverse Events (AE) (time frame: Within 30 minutes of vaccination). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03095599, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2019.

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