Influenza A/H5N1 Vaccine Clinical Trial (IVACFLU-A/H5N1) - Phase 1

• ClinicalTrials.gov Identifier: NCT02171819
• Recruitment Status: Completed
• First Posted: June 24, 2014
• Results First Posted: March 14, 2019
• Last Update Posted: March 14, 2019
• Sponsor: Institute of Vaccines and Medical Biologicals, Vietnam
• Collaborators: Department of Health and Human Services; World Health Organization; Institut Pasteur; PATH
• Information provided by (Responsible Party): Institute of Vaccines and Medical Biologicals, Vietnam

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Influenza A Subtype H5N1 Infection	Biological: IVACFLU-A/H5N1, 7.5 mcg; Biological: IVACFLU-A/H5N1, 15 mcg; Other: Placebo Comparator	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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 Start Date: June 2014
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: IVACFLU-A/H5N1, 7.5 mcg; IVACFLU-A/H5N1, 7.5 mcg HA per dose	Biological: IVACFLU-A/H5N1, 7.5 mcg; Contains 7.5 mcg HA and 0.6 mg of aluminum hydroxide adjuvant per 0.5 mL dose.
Experimental: IVACFLU-A/H5N1, 15 mcg; IVACFLU-A/H5N1, 15 mcg HA per dose.	Biological: IVACFLU-A/H5N1, 15 mcg; Contains 15 mcg HA and 0.6 mg of aluminum hydroxide adjuvant per 0.5 mL dose
Placebo Comparator: Placebo; Phosphate buffered saline	Other: Placebo Comparator; PBS, pH 7.2 in 0.5 mL single-dose vials.; Other Name: Phosphate Buffered Saline

Outcome Measures

Primary Outcome Measures :

1. Immediate Reactions Occurring Within 60 Minutes of Administration of Any Dose [ Time Frame: 60 min post injection ]
   Data presented are after 1st and 2nd vaccination combined. All participants were observed for immediate reactions for 60 minutes after administration of study product, with appropriate medical treatment readily available in case of an anaphylactic reaction following the administration of study product.
2. Number of Participants With at Least One Solicted Reactogenicity After Both Injections [ Time Frame: Within 7 days after injection ]

   Data presented are after 1st and 2nd vaccination combined. Solicted reactogenicity are local and systemic events that are expected after injection and specifically asked of the participant. Only reported reactogenicity is presented. If not shown, then no participant reported that reaction in any study group.

   Local reactions are redness, swelling, pain, tenderness, and hardness. Systemic reactions are actual and subjective fever, chills, cough, difficulty breathing, runny nose, nasal congestion, sore throat, hoarseness of voice, headache, confusion. convulsions/seizures, fatigue/malaise, muscle aches (generalized), joint pain, pink or red eyes, sore eyes, itchy eyes, drainage from eyes. ear pain or discharge, rash, abdominal pain, diarrhea, vomiting, and jaundice.

3. Number of Participants With at Least One Unsolicited AE [ Time Frame: Within 7 weeks of injection ]
   Summary of number of participants with at least one unsolicited AE after 1st and 2nd vaccination combined. Please see the adverse event section of this report for full details.
4. All Serious Adverse Events (SAEs) Occurring Within 3 Weeks of Receipt of Any Dose [ Time Frame: Within 3 weeks of any injection ]
   Summary data. Data presented are after 1st and 2nd injections combined. Please see AE reporting section of this report for full details.

Secondary Outcome Measures :

1. The Proportion of Subjects Achieving a Hemagglutination Inhibition (HAI) Titer ≥ 1:40 Pre-vaccination (Day 0) to Post 2nd Vaccination (Day 49) [ Time Frame: Day 0 to Day 49 ]
2. The Proportion of Subjects Achieving a Four-fold Rise in HAI Between Doses or From Baseline to Post-Injection 2 [ Time Frame: Days 21 and 42 ]
3. Geometric Mean Titer (GMT) of Hemagglutination Inhibition After Each Dose [ Time Frame: Days 0, 21 and 42 ]
4. Geometric Mean Titer (GMT) of Neutralizing Antibody After Each Dose [ Time Frame: Days 0, 21, and 42 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 30 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

Vietnam

Ben Luc Health Center

Bến Lức, Long An Province, Vietnam

Sponsors and Collaborators

Institute of Vaccines and Medical Biologicals, Vietnam

Department of Health and Human Services

World Health Organization

Institut Pasteur

PATH

Investigators

• Principal Investigator: Le Hoang San, MD; Pasteur Institute, Ho Chi Minh City

More Information

Additional Information:

Journal "Vaccine" on line by Elsevier 

Results of clinical trial published on line in the journal Vaccine 

Publications of Results:

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.

• Responsible Party: Institute of Vaccines and Medical Biologicals, Vietnam
• ClinicalTrials.gov Identifier: NCT02171819
• Other Study ID Numbers: IVAC A/H5N1; VAC021 ( Other Identifier: PATH )
• First Posted: June 24, 2014
• Results First Posted: March 14, 2019
• Last Update Posted: March 14, 2019
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Institute of Vaccines and Medical Biologicals, Vietnam:

Influenza; Avian; H5N1; Vaccine

Additional relevant MeSH terms:

Influenza, Human; Influenza in Birds; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases