Avian InfluenzaPhase 2/3NCT02612909
A Safety and Immunogenicity Study of IVACFLU-A/H5N1
A Phase 2/3 study testing IVACFLU-A/H5N1 vaccine in people with Avian Influenza, run by Institute of Vaccines and Medical Biologicals, Vietnam at 2 sites in Vietnam.
Trial summary
The study hypothesis was that two 0.5 mL doses of whole virion monovalent A/H5N1 influenza vaccine (IVACFLU-A/H5N1) adjuvanted with alum would be safe and well tolerated in healthy adults, and that at least one of the two doses tested would be immunogenic in 60% or more of the subjects tested. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Avian Influenza
- What is being tested?
- IVACFLU-A/H5N1 vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 930 participants
- Where
- 2 sitesVietnam
- Study dates
- 7 Mar 2017to 30 Aug 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
- Male or female adult 18 through 60 years of age at the enrollment visit.
- Literate (by self-report) 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 able to become pregnant, willing to utilize reliable birth control measures (intrauterine device, hormonal contraception, condoms) through the Day 43 visit.
Who cannot join
- Participation in another clinical trial involving any vaccine or therapy within the previous three months, or planned enrollment in such a trial during the period of this study.
- Received any non-study vaccine within 4 weeks prior to enrollment or refused to postpone receipt of such vaccines until after the Day 43 visit.
- Current or recent (within 2 weeks of enrollment) acute illness with or without fever.
- Received immune globulin or other blood products within 3 months prior to study enrollment or planned receipt of such products prior to the Day 43 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 meant prednisone or equivalent, 0.5 mg per kg per day; topical or intranasal steroids were allowed.)
- History of asthma.
Show all 21Show fewer
- 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 (Phase 2 only), which in the opinion of the investigator, might have interfered 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 immune deficient condition of any kind.
- Known Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) infection by self-report (Phase 3) or a positive test for either HBV surface antigen (HBsAg) or HCV antibody using anti-HCV test (Phase 2).
- Known HIV infection (self-report)
- Known active tuberculosis or symptoms of active tuberculosis (self-report).
- History of chronic alcohol abuse and/or illegal drug use.
- Pregnancy or lactation (a negative pregnancy test was required before administration of study product for all women of childbearing potential).
- History of Guillain-Barre Syndrome.
- Any condition in the opinion of the investigator that would have increased the health risk of the subject if he/she participated in the study or interfered with the evaluation of the study objectives.
- Note: Minor out-of-range laboratory values no greater than Grade 1 were not considered to be exclusionary at screening.
Trial locations and contacts
2 sites in 1 country.
Vietnam2 sites
Phase 3: Hai Phong Provincial Preventive Medicine Center
Haiphong, Hai Phong
Phase 2 & 3: Khanh Hoa Provincial Health Department
Nha Trang, Khanh Hoa
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 an Inactivated A/H5N1 Influenza Vaccine (IVACFLU-A/H5N1) Produced by IVAC
The study hypothesis was that two 0.5 mL doses of whole virion monovalent A/H5N1 influenza vaccine (IVACFLU-A/H5N1) adjuvanted with alum would be safe and well tolerated in healthy adults, and that at least one of the two doses tested would be immunogenic in 60% or more of the subjects tested.
Read the detailed description
Although the A/H1N1 (2009) pandemic has subsided and the virus has become endemic, the threat of another pandemic due to avian influenza A/H5N1 remains constant. Since 1997, highly pathogenic A/H5N1 avian viruses have caused both widespread outbreaks in poultry with high mortality and sporadic, severe, and fatal disease in humans. Southeast Asian countries, including Vietnam, have been affected by influenza A/H5N1. From 2003 through March 2015, WHO has reported 826 confirmed human cases of A/H5N1 influenza infection; including 440 fatal cases (World Health Organization, 2015). Southeast Asian countries accounted for 42% of all confirmed influenza A/H5N1 cases reported since 2003, and influenza A/H5N1 infection in animals is now thought to be endemic in the region (World Health Organization, 2015). As of March 2015, Vietnam has reported 127 confirmed human cases and 64 deaths. In 2014, two cases of A/H5N1 avian influenza were reported in Vietnam. Therefore, the risk of transmission to human is still present.
At the time of the study, no influenza A/H5N1 vaccine had been licensed in Vietnam. IVACFLU-A/H5N1 is an influenza A/H5N1 vaccine produced by Institute of Vaccines and Medical Biologicals (IVAC) using embryonated chicken eggs. IVACFLU-A/H5N1 is a whole virus vaccine, collected in a linear sucrose density gradient solution using a continuous flow centrifuge (Alfa Wassermann, West Caldwell, NJ) and inactivated with formaldehyde. The vaccine is alum adjuvanted. Vaccine strain NIBRG-14 derived from original influenza A/Vietnam/1194/2004 was provided to IVAC by the National Institute for Biological Standards and Control of the Health Protection Agency of the United Kingdom. A clinical trial of IVACFLU-A/H5N1 vaccine conducted in 75 subjects at the Ben Luc Health District in Vietnam in 2014 showed that the vaccine is safe and immunogenic at doses of 7.5 and 15 mcg.
This study was conducted in two stages: Phase 2 was a dose selection study where subjects were randomized to one of the three groups (15 mcg IVACFLU-A/H5N1 vaccine, 30 mcg IVACFLU-A/H5N1 vaccine or placebo) at a 1:1:1 ratio. The conduct of Phase 3 was dependent on showing hemagglutination inhibition (HAI) response titer of ≥1:40 in ≥60% of vaccine recipients in at least one of the two Phase 2 IVACFLU-A/H5N1 vaccine groups. Based on the review of immunogenicity and safety results from the Phase 2 study, a dose of study vaccine was selected for Phase 3. Subjects were randomized at two sites (Khanh Hoa and Hai Phong) to receive the IVACFLU-A/H5N1 vaccine dose selected in Phase 2 or placebo . Safety was assessed in all subjects and immunogenicity was measured in a subset of subjects at the Hai Phong study site.
- Conditions
- Avian Influenza
- Being tested
- IVACFLU-A/H5N1 vaccine, Placebo
- Keywords
- Avian Influenza, A/H5N1 vaccine, IVAC
- Medical subject headings
- Influenza in Birds
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IVACFLU-A/H5N1 vaccineBiological
Monovalent A/H5N1 influenza vaccine (MIV), whole virion inactivated, purified by sucrose gradient on ultracentrifuge. The vaccine was produced in eggs, inactivated with formaldehyde, and formulated with aluminum hydroxide 0.6 mg/0.5 mL with no preservative.
PlaceboBiological
Also called Sterile Phosphate Buffered Saline (PBS)
Includes 4.500mg sodium chloride, 0.685 mg sodium phosphate dibasic dihydrate, and 0.186 mg sodium phosphate monobasic dihydrate.
| Study group | Role | What they receive |
|---|---|---|
| Phase 2: Placebo | Placebo comparator | Subjects participating in Phase 2 and assigned to receiving two injections of placebo administered intramuscularly as a single dose, separated by 21 days. Receives: Biological: Placebo |
| Phase 2: Vaccine (15 mcg) | Active comparator | Subjects participating in Phase 2 and assigned to receiving two injections of IVACFLU-A/H5N1 vaccine (15 mcg concentration) administered intramuscularly as a single dose, separated by 21 days. Receives: Biological: IVACFLU-A/H5N1 vaccine |
| Phase 2: Vaccine (30 mcg) | Active comparator | Subjects participating in Phase 2 and assigned to receiving two injections of IVACFLU-A/H5N1 vaccine (30 mcg concentration) administered intramuscularly as a single dose, separated by 21 days. Receives: Biological: IVACFLU-A/H5N1 vaccine |
| Phase 3: Placebo | Placebo comparator | Subjects participating in Phase 3 and assigned to receiving two injections of placebo administered intramuscularly as a single dose, separated by 21 days. Receives: Biological: Placebo |
| Phase 3: Vaccine | Experimental | Subjects participating in Phase 2 and assigned to receiving two injections of IVACFLU-A/H5N1 vaccine (15 mcg concentration) administered intramuscularly as a single dose, separated by 21 days. Receives: Biological: IVACFLU-A/H5N1 vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and Percentage of Subjects Achieving a Hemagglutination Inhibition (HAI) Titer of ≥1:40
Serum specimens were tested for the presence of HAI antibodies to influenza. The HAI assay was conducted using serum samples from all the subjects in Phase 2 of the study and in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in Phase 3 in order to have at least 200 evaluable subjects receiving IVACFLU-A/H5N1 and 40 evaluable subjects receiving placebo, at the end of study.
Measured: Day 1, Day 43
Secondary outcomes (17)
Phase 2: Number and Percentage of Subjects Achieving a Hemagglutination Inhibition (HAI) Titer of ≥1:40
Serum specimens were tested for the presence of HAI antibodies to influenza. The HAI assay was conducted using serum samples from all the subjects in Phase 2 of the study and in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in Phase 3 in order to have at least 200 evaluable subjects receiving IVACFLU-A/H5N1 and 40 evaluable subjects receiving placebo, at the end of study.
Measured: Day 1, Day 22
Phase 2: Number and Percentage of Subjects Achieving at Least a 4-fold Increase in Hemagglutination Inhibition (HAI) Titer
Serum specimens were tested for the presence of HAI antibodies to influenza on day 1, day 22, and day 43 (day 1 and 22 prior to injection). The HAI assay was conducted using serum samples from all the subjects in Phase 2 of the study and in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in Phase 3 in order to have at least 200 evaluable subjects receiving IVACFLU-A/H5N1 and 40 evaluable subjects receiving placebo, at the end of study.
Measured: Day 22, Day 43
Phase 3: Number and Percentage of Subjects Achieving at Least a 4-fold Increase in Hemagglutination Inhibition (HAI) Titer
Serum specimens were tested for the presence of HAI antibodies to influenza. The HAI assay was conducted using serum samples from all the subjects in Phase 2 of the study and in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in Phase 3 in order to have at least 200 evaluable subjects receiving IVACFLU-A/H5N1 and 40 evaluable subjects receiving placebo, at the end of study.
Measured: Day 43
Phase 2: Geometric Mean Hemagglutination Inhibition (HAI) Titer
Serum specimens were tested for the presence of HAI antibodies to influenza on day 1, day 22, and day 43 (day 1 and 22 prior to injection). The HAI assay was conducted using serum samples from all the subjects in Phase 2 of the study and in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in Phase 3 in order to have at least 200 evaluable subjects receiving IVACFLU-A/H5N1 and 40 evaluable subjects receiving placebo, at the end of study.
Measured: Day 1, Day 22, Day 43
Phase 3: Geometric Mean Hemagglutination Inhibition (HAI) Titer
Serum specimens were tested for the presence of HAI antibodies to influenza. The HAI assay was conducted using serum samples from all the subjects in Phase 2 of the study and in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in Phase 3 in order to have at least 200 evaluable subjects receiving IVACFLU-A/H5N1 and 40 evaluable subjects receiving placebo, at the end of study.
Measured: Day 1, Day 43
Phase 2: Geometric Mean Hemagglutination Inhibition (HAI) Titer Ratio, With Respect to Day 1
Serum specimens were tested for the presence of HAI antibodies to influenza on day 1, day 22, and day 43 (day 1 and 22 prior to injection). The HAI assay was conducted using serum samples from all the subjects in Phase 2 of the study and in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in Phase 3 in order to have at least 200 evaluable subjects receiving IVACFLU-A/H5N1 and 40 evaluable subjects receiving placebo, at the end of study.
Measured: Day 22, Day 43
Phase 3: Geometric Mean Hemagglutination Inhibition (HAI) Titer Ratio, With Respect to Day 1
Serum specimens were tested for the presence of HAI antibodies to influenza. The HAI assay was conducted using serum samples from all the subjects in Phase 2 of the study and in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in Phase 3 in order to have at least 200 evaluable subjects receiving IVACFLU-A/H5N1 and 40 evaluable subjects receiving placebo, at the end of study.
Measured: Day 43
Number and Percentage of Subjects Experiencing Reactogenicity
Immediate reactogenicity (30 minutes post-injection) were evaluated on Day 1 and Day 22 and consisted of:
- Inspection of the upper arms for the presence or absence of redness, swelling, hardness, pain, or tenderness; and
- Documentation of the presence or absence of headache, fever, fatigue/malaise, muscle aches, joint aches, nausea, vomiting, or chills.
Immediate reactogenicity were assessed by a study physician or appropriately trained medical staff.
Measured: 30 minutes after each injection
Number and Percentage of Subjects Experiencing Reactogenicity
Reported solicited signs and symptoms were recorded by the subject on the Diary Card from Days 1-7 and Days 22-28 in the study, then evaluated by study physician on Days 8, 22, and 29.The evaluated solicited local reactogenicity events were as follows:
- Size of redness (at site of injection) in centimeters (cm)
- Size of swelling (at site of injection) in cm
- Size of induration (hardness at site of injection) in cm
- Pain (at site of injection)
- Tenderness (at site of injection)
The evaluated solicited systemic reactogenicity events were as follows:
- Fever/body temperature (and body location of measurement)
- Fatigue/malaise
- Generalized muscle aches
- Joint aches/pains
- Chills
- Nausea
- Vomiting
- Headache
Measured: 7 days after each vaccination
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events (AE)
Unsolicited AEs were any AEs that occurred any time after study product was given (temporally related to study product), whether or not deemed "related" to the product, and were not solicited. Unsolicited AEs were either observed by study staff while the subject was at a clinic for a study visit or reported by the subject at any time. Any solicited sign or symptom starting after 7 days post-study product injection was recorded as an "unsolicited AE".
For the Phase 2 study, laboratory results were considered AEs when the result was Grade 2 or above.
Any medical condition that was present at the time that the subject was enrolled was not reported as an AE, but was reported as a pre-existing condition on the Medical History Form. However, if this condition occurred with greater frequency or severity during the study, it was recorded as an AE.
Measured: 21 days after each vaccination
Number and Percentage of Subjects Experiencing Unsolicited Serious Adverse Events (SAE)
Defined as an adverse event that led to death, was life-threatening (subject at immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in congenital anomaly/birth defect; resulted in a persistent or significant disability or incapacity.
Measured: 90 days
Phase 2: Number and Percentage of Subjects Achieving at Least a 4-fold Increase in Neutralizing Antibody Titer
The microneutralization (MN) assay is an alternative assay for determining immunologic response to vaccination. It is a highly sensitive assay that can provide information on the ability of induced antibody to neutralize influenza virus. Titers of neutralizing antibodies were expressed as the amount of the greatest dilution of serum giving a neutralization of 50% of tissue cytopathic effects of the virus in the tissue culture.
Measured: Day 22, Day 43
Phase 3: Number and Percentage of Subjects Achieving at Least a 4-fold Increase in Neutralizing Antibody Titer
The MN assay is an alternative assay for determining immunologic response to vaccination. It is a highly sensitive assay that can provide information on the ability of induced antibody to neutralize influenza virus. Titers of neutralizing antibodies were expressed as the amount of the greatest dilution of serum giving a neutralization of 50% of tissue cytopathic effects of the virus in the tissue culture.
In Phase 3, MN assay was conducted in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in order to have at least 200 evaluable subjects receiving IVACFLU A/H5N1 and 40 evaluable subjects receiving placebo.
Measured: Day 43
Phase 2: Geometric Mean Neutralizing Antibody Titer
The microneutralization (MN) assay is an alternative assay for determining immunologic response to vaccination. It is a highly sensitive assay that can provide information on the ability of induced antibody to neutralize influenza virus. Titers of neutralizing antibodies were expressed as the amount of the greatest dilution of serum giving a neutralization of 50% of tissue cytopathic effects of the virus in the tissue culture.
Measured: Day 1, Day 22, Day 43
Phase 3: Geometric Mean Neutralizing Antibody Titer
Serum specimens were tested for the presence of HAI antibodies to influenza. The HAI assay was conducted using serum samples from all the subjects in Phase 2 of the study and in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in Phase 3 in order to have at least 200 evaluable subjects receiving IVACFLU-A/H5N1 and 40 evaluable subjects receiving placebo, at the end of study.
Measured: Day 1, Day 43
Phase 2: Geometric Mean Neutralizing Antibody Titer Ratio, With Respect to Day 1
The microneutralization (MN) assay is an alternative assay for determining immunologic response to vaccination. It is a highly sensitive assay that can provide information on the ability of induced antibody to neutralize influenza virus. Titers of neutralizing antibodies were expressed as the amount of the greatest dilution of serum giving a neutralization of 50% of tissue cytopathic effects of the virus in the tissue culture.
Measured: Day 22, Day 43
Phase 3: Geometric Mean Neutralizing Antibody Titer Ratio, With Respect to Day 1
The MN assay is an alternative assay for determining immunologic response to vaccination. It is a highly sensitive assay that can provide information on the ability of induced antibody to neutralize influenza virus. Titers of neutralizing antibodies were expressed as the amount of the greatest dilution of serum giving a neutralization of 50% of tissue cytopathic effects of the virus in the tissue culture.
In Phase 3, MN assay was conducted in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in order to have at least 200 evaluable subjects receiving IVACFLU A/H5N1 and 40 evaluable subjects receiving placebo.
Measured: Day 43
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2015 (estimated)
- Study start7 Mar 2017
- Primary completion29 Aug 2017
- Study completion30 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Avian InfluenzaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 930 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Vaccines and Medical Biologicals, Vietnam
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute of Hygiene and Epidemiology, Vietnam, World Health Organization, Department of Health and Human Services, PATH, FHI 360
- Responsible party
- Sponsor
- Investigators
- Tran N Duong, MD, PhD, Principal investigator, National Institute of Hygiene and Epidemiology, Vietnam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02612909
- Sponsor's protocol ID
- IVACFLU-A/H5N1-0203
- Status last verified
- May 2019
- First submitted
- 15 Oct 2015
- Last updated
- 21 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Duong TN, Thiem VD, Anh DD, Cuong NP, Thang TC, Huong VM, Chien VC, Phuong NTL, Montomoli E, Holt R, Scorza FB, Flores J, Tewari T. A Phase 2/3 double blinded, randomized, placebo-controlled study in healthy adult participants in Vietnam to examine the safety and immunogenicity of an inactivated whole virion, alum adjuvanted, A(H5N1) influenza vaccine (IVACFLU-A/H5N1). Vaccine. 2020 Feb 5;38(6):1541-1550. doi: 10.1016/j.vaccine.2019.11.059. Epub 2019 Dec 4.
PubMed 31812464
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 an Inactivated A/H5N1 Influenza Vaccine (IVACFLU-A/H5N1) Produced by IVAC
- ClinicalTrials.gov ID
- NCT02612909
- Acronym / sponsor ID
- IVACFLU-A/H5N1-0203
- Conditions
- Avian Influenza
- Keywords
- Avian Influenza, A/H5N1 vaccine, IVAC
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 930 participants (actual)
- Lead sponsor
- Institute of Vaccines and Medical Biologicals, VietnamIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Hygiene and Epidemiology, Vietnam, World Health Organization, Department of Health and Human Services, PATH, FHI 360
- Study start
- 7 Mar 2017 (actual)
- Primary completion
- 29 Aug 2017 (actual)
- Study completion
- 30 Aug 2017 (actual)
- First posted
- 24 Nov 2015 (estimated)
- Results
- Posted 16 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study hypothesis was that two 0.5 mL doses of whole virion monovalent A/H5N1 influenza vaccine (IVACFLU-A/H5N1) adjuvanted with alum would be safe and well tolerated in healthy adults, and that at least one of the two doses tested would be immunogenic in 60% or more of the subjects tested.
Detailed description
Although the A/H1N1 (2009) pandemic has subsided and the virus has become endemic, the threat of another pandemic due to avian influenza A/H5N1 remains constant. Since 1997, highly pathogenic A/H5N1 avian viruses have caused both widespread outbreaks in poultry with high mortality and sporadic, severe, and fatal disease in humans. Southeast Asian countries, including Vietnam, have been affected by influenza A/H5N1. From 2003 through March 2015, WHO has reported 826 confirmed human cases of A/H5N1 influenza infection; including 440 fatal cases (World Health Organization, 2015). Southeast Asian countries accounted for 42% of all confirmed influenza A/H5N1 cases reported since 2003, and influenza A/H5N1 infection in animals is now thought to be endemic in the region (World Health Organization, 2015). As of March 2015, Vietnam has reported 127 confirmed human cases and 64 deaths. In 2014, two cases of A/H5N1 avian influenza were reported in Vietnam. Therefore, the risk of transmission to human is still present.
At the time of the study, no influenza A/H5N1 vaccine had been licensed in Vietnam. IVACFLU-A/H5N1 is an influenza A/H5N1 vaccine produced by Institute of Vaccines and Medical Biologicals (IVAC) using embryonated chicken eggs. IVACFLU-A/H5N1 is a whole virus vaccine, collected in a linear sucrose density gradient solution using a continuous flow centrifuge (Alfa Wassermann, West Caldwell, NJ) and inactivated with formaldehyde. The vaccine is alum adjuvanted. Vaccine strain NIBRG-14 derived from original influenza A/Vietnam/1194/2004 was provided to IVAC by the National Institute for Biological Standards and Control of the Health Protection Agency of the United Kingdom. A clinical trial of IVACFLU-A/H5N1 vaccine conducted in 75 subjects at the Ben Luc Health District in Vietnam in 2014 showed that the vaccine is safe and immunogenic at doses of 7.5 and 15 mcg.
This study was conducted in two stages: Phase 2 was a dose selection study where subjects were randomized to one of the three groups (15 mcg IVACFLU-A/H5N1 vaccine, 30 mcg IVACFLU-A/H5N1 vaccine or placebo) at a 1:1:1 ratio. The conduct of Phase 3 was dependent on showing hemagglutination inhibition (HAI) response titer of ≥1:40 in ≥60% of vaccine recipients in at least one of the two Phase 2 IVACFLU-A/H5N1 vaccine groups. Based on the review of immunogenicity and safety results from the Phase 2 study, a dose of study vaccine was selected for Phase 3. Subjects were randomized at two sites (Khanh Hoa and Hai Phong) to receive the IVACFLU-A/H5N1 vaccine dose selected in Phase 2 or placebo . Safety was assessed in all subjects and immunogenicity was measured in a subset of subjects at the Hai Phong study site.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase 2: Placebo | Placebo comparator | Biological: PlaceboSubjects participating in Phase 2 and assigned to receiving two injections of placebo administered intramuscularly as a single dose, separated by 21 days. |
| Phase 2: Vaccine (15 mcg) | Active comparator | Biological: IVACFLU-A/H5N1 vaccineSubjects participating in Phase 2 and assigned to receiving two injections of IVACFLU-A/H5N1 vaccine (15 mcg concentration) administered intramuscularly as a single dose, separated by 21 days. |
| Phase 2: Vaccine (30 mcg) | Active comparator | Biological: IVACFLU-A/H5N1 vaccineSubjects participating in Phase 2 and assigned to receiving two injections of IVACFLU-A/H5N1 vaccine (30 mcg concentration) administered intramuscularly as a single dose, separated by 21 days. |
| Phase 3: Placebo | Placebo comparator | Biological: PlaceboSubjects participating in Phase 3 and assigned to receiving two injections of placebo administered intramuscularly as a single dose, separated by 21 days. |
| Phase 3: Vaccine | Experimental | Biological: IVACFLU-A/H5N1 vaccineSubjects participating in Phase 2 and assigned to receiving two injections of IVACFLU-A/H5N1 vaccine (15 mcg concentration) administered intramuscularly as a single dose, separated by 21 days. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male or female adult 18 through 60 years of age at the enrollment visit.
- Literate (by self-report) 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 able to become pregnant, willing to utilize reliable birth control measures (intrauterine device, hormonal contraception, condoms) through the Day 43 visit.
Key exclusion criteria (21 listed)
- Participation in another clinical trial involving any vaccine or therapy within the previous three months, or planned enrollment in such a trial during the period of this study.
- Received any non-study vaccine within 4 weeks prior to enrollment or refused to postpone receipt of such vaccines until after the Day 43 visit.
- Current or recent (within 2 weeks of enrollment) acute illness with or without fever.
- Received immune globulin or other blood products within 3 months prior to study enrollment or planned receipt of such products prior to the Day 43 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 meant prednisone or equivalent, 0.5 mg per kg per day; topical or intranasal steroids were allowed.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IVACFLU-A/H5N1 vaccineMonovalent A/H5N1 influenza vaccine (MIV), whole virion inactivated, purified by sucrose gradient on ultracentrifuge. The vaccine was produced in eggs, inactivated with formaldehyde, and formulated with aluminum hydroxide 0.6 mg/0.5 mL with no preservative. | Biological | Phase 2: Vaccine (15 mcg), Phase 2: Vaccine (30 mcg), Phase 3: Vaccine |
| PlaceboAlso: Sterile Phosphate Buffered Saline (PBS)Includes 4.500mg sodium chloride, 0.685 mg sodium phosphate dibasic dihydrate, and 0.186 mg sodium phosphate monobasic dihydrate. | Biological | Phase 2: Placebo, Phase 3: Placebo |
Primary outcome
Number and Percentage of Subjects Achieving a Hemagglutination Inhibition (HAI) Titer of ≥1:40
Time frame: Day 1, Day 43
Serum specimens were tested for the presence of HAI antibodies to influenza. The HAI assay was conducted using serum samples from all the subjects in Phase 2 of the study and in a subset of approximately 270 subjects receiving the IVACFLU-A/H5N1 vaccine (vaccinees) and placebo from one study site in Phase 3 in order to have at least 200 evaluable subjects receiving IVACFLU-A/H5N1 and 40 evaluable subjects receiving placebo, at the end of study.
17 secondary outcomes
Phase 2: Number and Percentage of Subjects Achieving a Hemagglutination Inhibition (HAI) Titer of ≥1:40
Time frame: Day 1, Day 22
Phase 2: Number and Percentage of Subjects Achieving at Least a 4-fold Increase in Hemagglutination Inhibition (HAI) Titer
Time frame: Day 22, Day 43
Phase 3: Number and Percentage of Subjects Achieving at Least a 4-fold Increase in Hemagglutination Inhibition (HAI) Titer
Time frame: Day 43
Phase 2: Geometric Mean Hemagglutination Inhibition (HAI) Titer
Time frame: Day 1, Day 22, Day 43
Phase 3: Geometric Mean Hemagglutination Inhibition (HAI) Titer
Time frame: Day 1, Day 43
Phase 2: Geometric Mean Hemagglutination Inhibition (HAI) Titer Ratio, With Respect to Day 1
Time frame: Day 22, Day 43
Phase 3: Geometric Mean Hemagglutination Inhibition (HAI) Titer Ratio, With Respect to Day 1
Time frame: Day 43
Number and Percentage of Subjects Experiencing Reactogenicity
Time frame: 30 minutes after each injection
Number and Percentage of Subjects Experiencing Reactogenicity
Time frame: 7 days after each vaccination
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events (AE)
Time frame: 21 days after each vaccination
Number and Percentage of Subjects Experiencing Unsolicited Serious Adverse Events (SAE)
Time frame: 90 days
Phase 2: Number and Percentage of Subjects Achieving at Least a 4-fold Increase in Neutralizing Antibody Titer
Time frame: Day 22, Day 43
Phase 3: Number and Percentage of Subjects Achieving at Least a 4-fold Increase in Neutralizing Antibody Titer
Time frame: Day 43
Phase 2: Geometric Mean Neutralizing Antibody Titer
Time frame: Day 1, Day 22, Day 43
Phase 3: Geometric Mean Neutralizing Antibody Titer
Time frame: Day 1, Day 43
Phase 2: Geometric Mean Neutralizing Antibody Titer Ratio, With Respect to Day 1
Time frame: Day 22, Day 43
Phase 3: Geometric Mean Neutralizing Antibody Titer Ratio, With Respect to Day 1
Time frame: Day 43
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31812464Duong TN, Thiem VD, Anh DD, Cuong NP, Thang TC, Huong VM, Chien VC, Phuong NTL, Montomoli E, Holt R, Scorza FB, Flores J, Tewari T. A Phase 2/3 double blinded, randomized, placebo-controlled study in healthy adult participants in Vietnam to examine the safety and immunogenicity of an inactivated whole virion, alum adjuvanted, A(H5N1) influenza vaccine (IVACFLU-A/H5N1). Vaccine. 2020 Feb 5;38(6):1541-1550. doi: 10.1016/j.vaccine.2019.11.059. Epub 2019 Dec 4.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tran N Duong, MD, PhD principal investigator
National Institute of Hygiene and Epidemiology, Vietnam
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing IVACFLU-A/H5N1 vaccine in people with Avian Influenza, run by Institute of Vaccines and Medical Biologicals, Vietnam at 2 sites 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 4 inclusion and 21 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 21 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 16 Apr 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 Achieving a Hemagglutination Inhibition (HAI) Titer of ≥1:40 (time frame: Day 1, Day 43). 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 NCT02612909, 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 21 May 2019.