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

NCT03095599 | Completed Phase 2 Results DMC

• 2 other identifiers: IVACFLU-S 0203CVIA 051
• Study Type: interventional
• Target: 889
• Locations: 1 country
• Sites: 1

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.

Conditions

Influenza, Human

Keywords

Influenza; Vaccine

Outcome Measures

Primary Outcomes (10)

• 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.

  Day 1 to Day 7

• 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

  Day 1 to Day 7

• 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.

  Day 1 to Day 21

• 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.

  Day 1 to Day 91

• 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

  Day 1, Day 22

• 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.

  Day 1, Day 22

• 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.

  Day 1, Day 22

Secondary Outcomes (5)

• 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

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

  Day 1, Day 22

• 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

• 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

• Geometric Mean Fold Change in HAI Antibody Titer, by Strain, Age Group, and Baseline Titer

  Day 1, Day 22

Study Arms (2)

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

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

Vaccine

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Institute of Vaccines and Medical Biologicals, Vietnam: lead
• Pasteur Institute, Ho Chi Minh City: collaborator
• PATH: collaborator
• Quintiles, Inc.: collaborator
• World Health Organization: collaborator

Study Sites (1)

Pasteur Institute, Ho Chi Minh City

Ho Chi Minh City, Vietnam

Location

Related Publications (1)

• 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.

  PMID: 31070986 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Le Van Be
• Organization: IVAC

ivaclevabe@dng.vnn.vn

(+84 90) 3501529

Study Officials

• Phan Cong Hung, MD

  Pasteur Institute, Ho Chi Minh City

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2017
• First Posted: March 29, 2017
• Study Start: March 20, 2017
• Primary Completion: October 5, 2017
• Study Completion: October 5, 2017
• Last Updated: July 22, 2019
• Results First Posted: July 22, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

VN (1)