Clinical trial NCT02171819: Influenza A/H5N1 Vaccine Clinical Trial (IVACFLU-A/H5N1) - Phase 1
Official title: A Phase 1 Double Blinded, Randomized, Placebo-Controlled Study to Examine the Safety and Immunogenicity of an Inactivated A/H5N1 Influenza Vaccine (IVACFLU-A/H5N1) Produced by IVAC in Healthy Adult Volunteers in Vietnam
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza A Subtype H5N1 Infection
Keywords: Influenza
Avian
H5N1
Vaccine
Lead sponsor: Institute of Vaccines and Medical Biologicals, Vietnam
Sponsor class: INDUSTRY
Collaborators: name: Department of Health and Human Services
name: World Health Organization
name: Institut Pasteur
name: PATH
First posted: 2014-06-24
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This is a first-in-human study of safety and immunogenicity of an A/H5N1 inactivated whole cell vaccine when given in two injections in two doses (low and high) compared to a placebo in 76 healthy adult subjects in Vietnam. Vaccine and placebo are manufactured by the IVAC in Vietnam.

Detailed description: This is a phase 1, double blinded, randomized, placebo-controlled study. Seventy-six healthy male and female adults, 18 to 30 years of age, will be enrolled into the trial. Subjects will be randomized to one of three treatment allocations: 32 subjects to 7.5 mcg/dose vaccine (low dose), 32 subjects to 15 mcg/dose vaccine (high dose) and 12 subjects to placebo. This sample size was selected to enable at least 30 evaluable subjects in each of the groups receiving active vaccine. The study will utilize a "block randomization" to assure a balance of 8:8:3 vaccine and placebo when all subjects are enrolled. The study will be double blinded, meaning the study subjects, investigators, and the sponsor will be unaware of the treatment allocated to each subject until the clinical trial database is declared final and locked.

Since this is a first-in-human study, all injections of study product will be sequential and staggered and there will be a safety evaluation between a sentinel cohort of 19 subjects and the remaining 57 study subjects for both the 1st and 2nd doses in the study.

A sentinel group of 19 participants' enrollment and vaccination will precede the remainder of the study group by approximately 2-3 weeks.

Product administration for both injections of vaccine or placebo will be sequential and staggered.

Eligibility criteria: Inclusion Criteria:

* Male or female adult 18 through 30 years of age at the enrollment visit.
* Literate and willing to provide written informed consent.
* Healthy adults, as established by the medical history and screening evaluations, including physical examination.
* 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 (intrauterine device, hormonal contraception, condoms) through the Day 42 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 four weeks prior to enrollment or refusal to postpone receipt of such vaccines until after the Day 42 visit.
* Current or recent (within two weeks of enrollment) acute illness with or without fever.
* Receipt of immune globulin or other blood products within three months prior to study enrollment or planned receipt of such products prior to the Day 42 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.
* Other AE following immunization, at least possibly related to previous receipt of any vaccine.
* Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein.
* Known hypersensitivities (allergies) to food or the natural environment.
* 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.
* Known chronic HBV or HCV infection.
* Known active tuberculosis or symptoms of active tuberculosis, regardless of cause.
* 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.

Primary outcomes:
measure: Immediate Reactions Occurring Within 60 Minutes of Administration of Any Dose
timeFrame: 60 min post injection
measure: Number of Participants With at Least One Solicted Reactogenicity After Both Injections
timeFrame: Within 7 days after injection
measure: Number of Participants With at Least One Unsolicited AE
timeFrame: Within 7 weeks of injection
measure: All Serious Adverse Events (SAEs) Occurring Within 3 Weeks of Receipt of Any Dose
timeFrame: Within 3 weeks of any injection
Secondary outcomes:
measure: The Proportion of Subjects Achieving a Hemagglutination Inhibition (HAI) Titer ≥ 1:40 Pre-vaccination (Day 0) to Post 2nd Vaccination (Day 49)
timeFrame: Day 0 to Day 49
measure: The Proportion of Subjects Achieving a Four-fold Rise in HAI Between Doses or From Baseline to Post-Injection 2
timeFrame: Days 21 and 42
measure: Geometric Mean Titer (GMT) of Hemagglutination Inhibition After Each Dose
timeFrame: Days 0, 21 and 42
measure: Geometric Mean Titer (GMT) of Neutralizing Antibody After Each Dose
timeFrame: Days 0, 21, and 42
Other outcomes:
Locations:
city: Bến Lức
country: Vietnam
facility: Ben Luc Health Center
state: Long An Province
Study officials:
affiliation: Pasteur Institute, Ho Chi Minh City
name: Le Hoang San, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Phan TL, Ho VT, Vu MH, Nguyen TN, Duong HT, Holt R, Wahid R, Donnelly J, Flores J. Clinical testing of an inactivated influenza A/H5N1 vaccine candidate in a double-blinded, placebo-controlled, randomized trial in healthy adults in Vietnam. Vaccine. 2016 Oct 26;34(45):5449-5456. doi: 10.1016/j.vaccine.2016.08.055. Epub 2016 Aug 31.