Safety of the Seasonal Trivalent Inactivated Split Virion Influenza Vaccine (IVACFLU-S)

Influenza Clinical Trial

— IVACFLU-S  

Official title:

A Phase 1 Double Blinded, Randomized, Placebo Controlled Study in Vietnamese Healthy Adult Volunteers to Assess the Safety and Immunogenicity of a Seasonal Trivalent Inactivated Split Vision Influenza Vaccine (IVACFLU-S) Produced by IVAC

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02809209
• Other study ID #: 2015-IVACFLUSPLIT-01
• Secondary ID: 84-CN-BDGDD
• Status: Completed
• Phase: Phase 1
• First received: May 31, 2016
• Last updated: June 21, 2016
• Start date: October 2015
• Est. completion date: April 2016

Study information

• Verified date: June 2016
• Source: National Institute of Hygiene and Epidemiology, Vietnam
• Contact: n/a
• Is FDA regulated: No
• Health authority: Vietnam: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This is a phase I, double-blind, randomized, placebo-controlled trial with two groups of subjects to assess the safety of the seasonal trivalent inactivated split virion influenza vaccine (A/H1N1; A/H3N2 and B strains). A total of 60 healthy male and female adults, aged from 18 through 45 years will be randomized to receive the vaccine (n=30) or placebo (n=30). In addition, immune responses induced by the vaccine will be evaluated.

Description:

A single dose of seasonal trivalent inactivated split virion influenza vaccine (IVACFLU-S) at the dose level tested will be tested for safety and immunogenicity in healthy adults.

The vaccine is produced in eggs, and formalin -inactivated, purified through sucrose gradient ultracentrifugation in IVAC facility. Each dose of the vaccine contains 15 mcg of each of the three components per 0.5 mL. The vaccine strains are:

• NYMC BX-51B reassortant of B/Massachusetts/2/2012

• NYMC X‐179A reassortant of A/California/7/2009 (H1N1)

• NYMC X-223A reassortant of H3/A/Texas/50/2012 (H3N2)

The vaccine safety profile will be assessed by the number and percentage of subjects with, the following:

• Adverse events occurring over the immediate 30-minute post-vaccination period.

• Solicited local reactogenicity, including redness, swelling, induration, pain and tenderness over a 7-day period (Days 1-7) post-vaccination.

• Solicited systemic reactogenicity, including fever, fatigue/malaise, muscle aches, joint aches, chills, nausea, vomiting, and headache over a 7-day period (Days 1-7) post-vaccination.

• Abnormal laboratory values observed post-vaccination (Day 8) in comparison to baseline values (Day 1).

• Unsolicited adverse events occurring within 21 days post vaccination.

• Serious adverse events (SAEs) occurring over the entire study period (Day 91).

The immunogenicity assessment against each one of the vaccine components includes:

• Numbers and percentages of subjects with a serum Hemagglutination Inhibition (HAI) antibody titer ≥ 1:40 to each of the 3 vaccine components measured on Day 22 post-vaccination.

• Numbers and percentages of subjects seroconverted against each of the 3 antigens on Day 22 post-vaccination. Seroconversion is defined as a serum HAI titer meeting the following criteria:

• pre-vaccination titer <1:10 and a post-vaccination titer ≥ 1:40 or

• pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination measured on Day 22.

• Geometric mean titers (GMTs) of serum HAI antibodies pre- (Day 1) and post-vaccination (Day 22) for each of the 3 antigens.

• Numbers and percentages of subjects with four-fold rise from baseline for each of the influenza vaccine strain-specific H1, H3, and B microneutralizing antibodies (MNT).

• Geometric mean antibody titers of neutralizing antibodies (MNT) pre- (Day 1) and post-vaccination (Day 22) for each of the 3 antigens.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: April 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Male or female adult 18 through 45 years of age at the enrollment visit.

• Literate (by self-report) and willing to provide written informed consent.

• Healthy, as established by the medical history, physical examination, and screening laboratory evaluations.

• Capable and willing to complete Diary Cards and willing to return for all follow-up visits.

• For females, willing to utilize reliable birth control measures (e.g., intrauterine device, hormonal contraception, condoms) through the Day 22 visit.

Exclusion Criteria:

• Participation in another clinical trial involving any therapy within the previous three months or planned enrollment in such a trial 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.

• Current or recent (within 2 weeks of enrollment) acute illness with or without fever.

• 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.

• Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study enrollment. (For corticosteroids, this means prednisone or equivalent, = 0.5 mg per kg per day; topical steroids are allowed.)

• History of asthma.

• Hypersensitivity after previous administration of any vaccine.

• Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein, antibiotics, and rubber (from the vaccine vial stoppers).

• Acute or chronic clinically significant pulmonary, cardiovascular, hepatobiliary, metabolic, neurologic, psychiatric or renal functional abnormality, as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives.

• History of any blood or solid organ cancer.

• History of thrombocytopenic purpura or known bleeding disorder.

• History of seizures.

• Known or suspected immunosuppressed or immunodeficient condition of any kind.

• Confirmed HBV or HCV infection

• Known HIV infection (self-report).

• Known active tuberculosis or symptoms of active tuberculosis, regardless of cause (self-report).

• History of chronic alcohol abuse and/or illegal drug use.

• Pregnancy or lactation. (A negative pregnancy test will be required before administration of study product for all women of childbearing potential.)

• History of Guillain-Barré Syndrome

• 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.

Note: Minor out-of-range laboratory values no greater than Grade 1 (see toxicity table in Appendix) will not be considered to be exclusionary at screening.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• IVACFLU-S
Seasonal trivalent inactivated influenza vaccine (TIV), inactivated split virion, purified by sucrose gradient ultracentrifugation, produced in eggs, and inactivated with formaldehyde will be administered intramuscularly as a single dose. Each dose of vaccine contains 15 mcg of each of the three strains in total volume of 0.5 mL. The vaccine strains are NYMC BX-51B reassortant of B/Massachusetts/2/2012 NYMC X-179A reassortant of A/California/7/2009 (H1N1) NYMC X-223A reassortant of H3/A/Texas/50/2012 (H3N2)
• Placebo
Placebo which is phosphate buffer saline,pH 7.2 is manufactured by IVAC. Placebo will also be packaged in 0.5 mL single-dose vials and administered intramuscularly.

Locations

Country	Name	City	State
Vietnam	Hung Ha district preventive medicine centre	Thai Binh
Vietnam	Thai Binh Preventive Medicine Center	Thai Binh

Sponsors (4)

Lead Sponsor	Collaborator
National Institute of Hygiene and Epidemiology, Vietnam	PATH, Thai Binh Center of Preventive Medicine, Thai Binh, Vietnam, World Health Organization

Country where clinical trial is conducted

Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants with unsolicited adverse events occurring post vaccination.	Unsolicited adverse events	21 days post-vaccination	Yes
Primary	Numbers of subjects with treatment-related adverse events immediately and within 7 days after vaccination	Numbers of person with; Adverse events occurring within 30-minute post-vaccination period.; Solicited local reactogenicity, including redness, swelling, induration, pain and tenderness over a 7-day period (Days 1-7) post-vaccination.; Solicited systemic reactogenicity, including fever, fatigue/malaise, muscle aches, joint aches, chills, --nausea, vomiting, and headache over a 7-day period (Days 1-7) post-vaccination.	7 days after vaccination	Yes
Secondary	Number of participants with abnormal laboratory values	Numbers of participants with abnormal laboratory values (Blood cell counts, urea concentration, AST-ALT concentration) when administered with IVACFLU-S	7 days after vaccination	Yes
Secondary	Numbers of participants with treatment-related serious adverse events (SAEs) during study period	Numbers of participants with treatment related SAE after vaccination with IVACFLU-S	90 days after vaccination	Yes
Secondary	Numbers of subjects with a serum Hemagglutination Inhibition (HAI) antibody titer to each of the 3 vaccine components >=40	Numbers of participants with HAI titers >=40	21 days post-vaccination	No
Secondary	Numbers of subjects seroconverted against each of the 3 antigens after vaccination	Number of participants seroconvert with serum HAI antibody titers as follows: pre-vaccination titer <1:10 and a post-vaccination titer = 1:40 or; pre-vaccination titer = 1:10 and at least a four-fold increase in post-vaccination measured 21 days post-vaccination	21 days post-vaccination	No
Secondary	Geometric mean titers (GMTs) of serum HAI antibodies pre- and post-vaccination for each of the 3 antigens of all participants	Compare GMT of HAI between vaccine and placebo groups.	21 days post-vaccination	No
Secondary	Numbers of subjects with four-fold rise from baseline for each of the influenza vaccine strain-specific H1, H3, and B neutralizing antibodies (MNT).	Numbers of participants with 4-fold or more rises in neutralising antibodies specific to 3 vaccine strains	21 days post-vaccination	No
Secondary	Geometric mean neutralization titers of neutralizing antibodies (MNT) pre- and post-vaccination for each of the 3 antigens.	Compare GMT of neutralising antibodies between vaccine and placebo groups	21 days post-vaccination	No