InfluenzaPhase 1NCT01507779
Safety Trial of Monovalent Whole Virus Influenza (H1N1) Vaccine
A Phase 1 study testing IVACFLU in people with Influenza, run by PATH at 1 site in Vietnam.
Trial summary
The study hypothesis is that two 0.5 ml doses of non-adjuvanted whole virion monovalent A/H1N1 influenza vaccine (IVACFLU)--each dose with an HA content of 15 mcg from A/California/07/2009 (H1N1)-like virus--will be safe and immunogenic in healthy adults. Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- IVACFLU
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteVietnam
- Study dates
- Apr 2012to Dec 2012
- Phase
- Phase 1
- 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 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female adult 18 (age of legal consent in Vietnam) through 40 years of age at the enrollment visit.
- Literate and willing to provide written informed consent.
- Free of obvious health problems, 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, birth control pills, condoms) through the Day 42 visit.
Who cannot join
- 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.
Show all 21Show fewer
- 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, hepatic, 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 leukemia or any other 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, including HIV infection.
- 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 vaccine or placebo for all women of childbearing potential.)
- History of Guillain-Barre' 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of The Safety and Immunogenicity of an Influenza A/H1N1 Vaccine (IVACFLU), Produced by IVAC, in Healthy Adults in Vietnam
The study hypothesis is that two 0.5 ml doses of non-adjuvanted whole virion monovalent A/H1N1 influenza vaccine (IVACFLU)--each dose with an HA content of 15 mcg from A/California/07/2009 (H1N1)-like virus--will be safe and immunogenic in healthy adults.
Read the detailed description
This is a phase I, double-blind, individually-randomized (1:1, vaccine:placebo), controlled trial with two groups, IVACFLU (A/H1N1) and placebo. Healthy male and female adults 18 through 40 years of age will be invited to participate. In addition to sponsor monitoring of safety, Program for Appropriate Technology in Health (PATH) will review safety data. Safety data through 7 days post-dose one for all subjects will be reviewed in a blinded fashion prior to administration of dose two of study vaccine or placebo. PATH will review all adverse events (AEs), including clinical laboratory evaluations (pre- and post-vaccination) and will advise if the volunteers may receive dose two of study vaccine or placebo. For all subjects, the procedures and timelines are summarized below.
On the day of first screening (S1), about 14 days (between 5 and 30 days) prior to administration of dose one of study vaccine or placebo, subjects will be screened for eligibility through medical history review, physical examination, testing for serologic evidence of chronic viral infection [human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)], routine biochemical and hematological blood tests and urinalysis by dipstick. For screening for serologic evidence of chronic viral infections, appropriate pre- and post-test counseling must be provided.
Subject screening for eligibility will continue and be completed on the second screening day (S2). This second screening day will occur the same day as scheduled enrollment into the trial and administration of study vaccine or placebo (Day 0). Women will undergo pregnancy tests using urine samples on Day 0. Fully eligible subjects will be enrolled into the trial. At that time, blood specimens will be collected for immunological testing prior to administration of study vaccine or placebo. Subjects will be unaware of which allocation, IVACFLU or placebo, is received; study vaccine and placebo will be masked. Subjects will be carefully monitored for adverse reactions for 60 minutes after vaccination.
During the first week following vaccination, subjects will be asked to record local and general signs and symptoms using preprinted diary cards, thermometer, and small ruler. Concomitant medications will also be recorded. In addition to solicited signs, subjects will be asked to report any other adverse events, whether or not they believe that the event is related to the vaccination. Member of the investigator's clinical team will visit subjects one and five days after vaccination to check that subjects are correctly completing the diary card and to check on the subjects' well-being. Subjects will then return to the study clinic 7 days after dose one. At that time, the investigator will check the subjects' diary cards and transcribe all adverse events onto the case report forms using medical language. Blood and urine specimens will also be collected for routine biochemical and hematological blood tests and urinalysis by dipstick.
Two days before subjects are scheduled to receive dose two, subjects will be visited or called to remind them of the next visit to the study clinic and to check on the subjects' well-being. Subjects will return to the study clinic at 3 weeks after administration of dose one of study vaccine or placebo in order to receive dose two. At that time, interim histories and concomitant medications will be reviewed. Women will again undergo urine pregnancy tests. All subjects will undergo collection of blood and urine specimens for routine biochemical and hematological blood tests and urinalysis by dipstick and collection of blood serum specimens for immunologic analyses. Then subjects will receive dose two of study vaccine or placebo and be monitored for 60 minutes.
After receipt of dose two, subjects will again complete diary cards for 7 days after vaccination with visits by members of the investigator's clinical team again at days one and five after vaccination to check that the subjects are correctly completing diary cards and to check on the subjects' well-being. Subjects will then return to the study clinic 7 days after dose two (Day 28) for review of diary cards by the investigator and collection of blood and urine specimens for routine biochemical and hematological blood tests and urinalysis by dipstick.
Two days before the subjects' next scheduled visit at 3 weeks after administration of dose two, subjects will be visited or called to remind them of the next visit to the study clinic and to check on the subjects' well-being. Subjects will then return to the study clinic at 3 weeks after administration of dose two (Day 42) of study vaccine or placebo for another study visit. At that time, interim histories and concomitant medications will again be reviewed and final blood specimens will be collected for immunogenicity analyses. Women will also undergo a final pregnancy screen.
Subjects will then be asked to immediately report severe adverse events (SAEs) which occur from Day 42 to Day 201 (approximately 6 months after receipt of dose two). To facilitate this reporting, a member of the investigator's team will visit or call the subjects monthly to check on their well-being. At last study visit on Day 201, subjects will be interviewed and examined one last time before completing the study.
For the evaluation of serum antibodies (by hemagglutination inhibition and microneutralization), serum specimens will be collected on Day 0 (prior to administration of dose one of study vaccine or placebo), on Day 21 (prior to administration of dose two of study vaccine or placebo) and on Day 42.
- Conditions
- Influenza
- Being tested
- IVACFLU, Placebo
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IVACFLUBiological
Also called whole virion monovalent A/H1N1 influenza vaccine
IVACFLU is a whole virus vaccine, collected in a linear sucrose density gradient solution using a continuous flow centrifuge Alfpa Wassmann and inactivated with formaldehyde. It was formulated to contain 15 mcg hemagglutinin (HA) of influenza A/California/07/2009(H1N1)-like virus per 0.5 mL dose and filled in single dose vials.
PlaceboOther
Phosphate buffered saline (PBS), pH 7.2, in 0.5 ml single-dose vials.
| Study group | Role | What they receive |
|---|---|---|
| Influenza vaccine | Experimental | Received 0.50 mL of inactivated monovalent influenza vaccine (IVACFLU), administered intramuscularly, on days 0 and 21 Receives: Biological: IVACFLU |
| Placebo | Placebo comparator | Received placebo, administered intramuscularly, on days 0 and 21 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Maximum Systemic Reaction After Vaccination 1
Systemic and local reactogenicity data were collected on Study Days 0, 7, 21 and 28, prevaccination, and within 60 minutes post-vaccination by clinic staff. Subjects completed diary cards for 7 days after each vaccination and received visits from the investigator's clinical team at Days 1 and 5 following each vaccination. Solicited systemic reactogenicity events included body temperature, feverishness, chills, cough, difficulty breathing, runny nose, nasal congestion, sore throat, hoarseness of voice, headache, confusion, convulsions/seizures, fatigue/malaise, muscle aches, joint pain, pink or red eyes, sore eyes, itchy eyes, drainage from eyes, ear pain or discharge, rash, abdominal pain, diarrhea, vomiting and jaundice. Solicited local reactogenicity included size of redness, size of swelling, size of induration, pain, and tenderness.
Measured: 7 days
Number of Participants With Maximum Systemic Reaction After Vaccination 2
Systemic and local reactogenicity data were collected on Study Days 0, 7, 21 and 28, prevaccination, and within 60 minutes post-vaccination by clinic staff. Subjects completed diary cards for 7 days after each vaccination and received visits from the investigator's clinical team at Days 1 and 5 following each vaccination. Solicited systemic reactogenicity events included body temperature, feverishness, chills, cough, difficulty breathing, runny nose, nasal congestion, sore throat, hoarseness of voice, headache, confusion, convulsions/seizures, fatigue/malaise, muscle aches, joint pain, pink or red eyes, sore eyes, itchy eyes, drainage from eyes, ear pain or discharge, rash, abdominal pain, diarrhea, vomiting and jaundice. Solicited local reactogenicity included size of redness, size of swelling, size of induration, pain, and tenderness.
Measured: 7 days
Number of Participants With Maximum Local Reaction After Vaccination 1
Systemic and local reactogenicity data were collected on Study Days 0, 7, 21 and 28, prevaccination, and within 60 minutes post-vaccination by clinic staff. Subjects completed diary cards for 7 days after each vaccination and received visits from the investigator's clinical team at Days 1 and 5 following each vaccination. Solicited local reactogenicity included size of redness, size of swelling, size of induration, pain, and tenderness.
Measured: 7 days
Number of Participants With Maximum Local Reaction After Vaccination 2
Systemic and local reactogenicity data were collected on Study Days 0, 7, 21 and 28, prevaccination, and within 60 minutes post-vaccination by clinic staff. Subjects completed diary cards for 7 days after each vaccination and received visits from the investigator's clinical team at Days 1 and 5 following each vaccination. Solicited local reactogenicity included size of redness, size of swelling, size of induration, pain, and tenderness.
Measured: 7 days
Unsolicited, Non-serious Adverse Events
Subjects completed diary cards for 7 days after each vaccination and received visits from the investigator's clinical team at Days 1 and 5 following each vaccination. Adverse events were collected throughout the study period, and were graded for severity; however unsolicited adverse events were assessed only for relationship to vaccine if the events were immediate reactions or considered to be serious adverse events.
Measured: 7 days after each dose (Day 7 and Day 28)
Secondary outcomes (12)
Geometric Mean Titer of Hemagglutination-inhibition Antibodies (HAI)
Day 0, 21 and 42 blood samples from study subjects (n=48) were tested. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The hemagglutination titer was reported as the reciprocal of the highest dilution that caused hemagglutination and was expressed in HA units (HAU)/50μL, calculated as the average of results of duplicate wells.
Measured: Day 0, Day 21 and Day 42
Ratio of Geometric Mean Titer of Hemagglutination-inhibition Antibodies (HAI)
Day 0, 21 and 42 blood samples from study subjects (n=48) were tested. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The hemagglutination titer was reported as the reciprocal of the highest dilution that caused hemagglutination and was expressed in HA units (HAU)/50μL, calculated as the average of results of duplicate wells.
Measured: Day 0, Day 21 and Day 42
Number and Percentage of All Subjects Achieving a Four-fold Rise in Hemagglutination-inhibition Antibodies (HAI)
Day 21 and 42 blood samples from study subjects (n=48) were tested. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The hemagglutination titer was reported as the reciprocal of the highest dilution that caused hemagglutination and was expressed in HA units (HAU)/50μL, calculated as the average of results of duplicate wells.
Measured: Day 21 and Day 42
Number and Percentage of Subjects Achieving a Four-fold Rise in Hemagglutination-inhibition Antibodies (HAI) Among Subjects With Baseline Titer Less Than 40
Day 21 and Day 42 blood samples from study subjects (n=48) were tested. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The hemagglutination titer was reported as the reciprocal of the highest dilution that caused hemagglutination and was expressed in HA units (HAU)/50μL, calculated as the average of results of duplicate wells.
Measured: Day 21 and Day 42
Number and Percentage of Subjects Achieving a Four-fold Rise in Hemagglutination-inhibition Antibodies (HAI) Among Subjects With Baseline Titer Greater Than 40
Day 21 and 42 blood samples from study subjects (n=48) were tested. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The hemagglutination titer was reported as the reciprocal of the highest dilution that caused hemagglutination and was expressed in HA units (HAU)/50μL, calculated as the average of results of duplicate wells.
Measured: Day 21 and Day 42
Number and Percentage of Subjects Developing a Seroprotective Hemagglutination-inhibition (HAI) Antibody Titer
Seroprotection defined as an HAI titer ≥1:40. Day 21 and 42 blood samples from study subjects (n=48) were tested. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The hemagglutination titer was reported as the reciprocal of the highest dilution that caused hemagglutination and was expressed in HA units (HAU)/50μL, calculated as the average of results of duplicate wells.
Measured: Day 21 and Day 42
Geometric Mean Titer of Microneutralizing (MN) Antibodies
Day 0, 21 and 42 specimens were tested in the microneutralization (MN) assay. The microneutralization assay determines the titer of neutralizing antibodies against influenza A/H1N1. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The 50% neutralizing antibody titer is the reciprocal of the corresponding serum dilution. The geometric mean titers (GMT) and corresponding confidence intervals were based on a log 10 scale.
Measured: Day 0, Day 21 and Day 42
Ratio of Geometric Mean Titer of Microneutralization (MN) Antibodies
Day 0, 21 and 42 specimens were tested in the microneutralization (MN) assay. The microneutralization assay determines the titer of neutralizing antibodies against influenza A/H1N1. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The 50% neutralizing antibody titer is the reciprocal of the corresponding serum dilution. The geometric mean titers (GMT) and corresponding confidence intervals were based on a log 10 scale.
Measured: Day 0, Day 21 and Day 42
Number and Percentage of All Subjects Achieving a Four-fold Rise in Microneutralization (MN) Antibodies
Day 21 and 42 specimens were tested in the microneutralization (MN) assay. The microneutralization assay determines the titer of neutralizing antibodies against influenza A/H1N1. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The 50% neutralizing antibody titer is the reciprocal of the corresponding serum dilution. The geometric mean titers (GMT) and corresponding confidence intervals were based on a log 10 scale.
Measured: Day 21 and Day 42
Number and Percentage of Subjects Achieving a Four-fold Rise in Microneutralizing (MN) Antibodies Among Subjects With Baseline Titer Less Than 40
Day 21 and 42 blood samples from study subjects (n=48) were tested. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The hemagglutination titer was reported as the reciprocal of the highest dilution that caused hemagglutination and was expressed in HA units (HAU)/50μL, calculated as the average of results of duplicate wells.
Measured: Day 21 and Day 42
Number and Percentage of Subjects Achieving a Four-fold Rise in Microneutralizing (MN) Antibodies Among Subjects With Baseline Titer Greater Than 40
Day 21 and 42 specimens were tested in the microneutralization (MN) assay. The microneutralization assay determines the titer of neutralizing antibodies against influenza A/H1N1. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The 50% neutralizing antibody titer is the reciprocal of the corresponding serum dilution. The geometric mean titers (GMT) and corresponding confidence intervals were based on a log 10 scale.
Measured: Day 21 and Day 42
Number and Percentage of Subjects Developing a Seroprotective Microneutralizing (MN) Antibody Titer
Seroprotection defined as an antibody titer of 1:40 or greater. Day 21 and 42 specimens were tested in the microneutralization (MN) assay. The microneutralization assay determines the titer of neutralizing antibodies against influenza A/H1N1. The assay is performed in duplicate wells of 2-fold serial dilutions of serum. The 50% neutralizing antibody titer is the reciprocal of the corresponding serum dilution. The geometric mean titers (GMT) and corresponding confidence intervals were based on a log 10 scale.
Measured: Day 21 and Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2012 (estimated)
- Study startApr 2012
- Primary completionNov 2012
- Study completionDec 2012
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 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Collaborators
- Institute of Vaccines and Medical Biologicals, Vietnam, Pasteur Institute, Ho Chi Minh City
- Responsible party
- Sponsor
- Investigators
- Kathleen M Neuzil, MD, MPH, Study director, PATHLe V Be, MD, PhD, Study director, Institute of Vaccines and Medical Biologicals, VietnamHo V Thang, MD, MSc, Principal investigator, Pasteur Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01507779
- Sponsor's protocol ID
- IVAC-mH1N1-01
- Status last verified
- Feb 2019
- First submitted
- 6 Jan 2012
- Last updated
- 27 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Thang HV, Huong VM, Victor JC, Van CB, Nga NT, Be LV, Cuong NP, Tsvetnitsky V, Neuzil KM, Power M, Flores J. Safety and immunogenicity of inactivated monovalent influenza A/H1N1 vaccine candidate manufactured in Vietnam. Vaccine. 2018 Nov 12;36(46):6918-6925. doi: 10.1016/j.vaccine.2018.10.013. Epub 2018 Oct 15.
PubMed 30337172
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of The Safety and Immunogenicity of an Influenza A/H1N1 Vaccine (IVACFLU), Produced by IVAC, in Healthy Adults in Vietnam
- ClinicalTrials.gov ID
- NCT01507779
- Acronym / sponsor ID
- IVAC-mH1N1-01
- Conditions
- Influenza
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Collaborators
- Institute of Vaccines and Medical Biologicals, Vietnam, Pasteur Institute, Ho Chi Minh City
- Study start
- Apr 2012
- Primary completion
- Nov 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 11 Jan 2012 (estimated)
- Results
- Posted 27 Feb 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 is that two 0.5 ml doses of non-adjuvanted whole virion monovalent A/H1N1 influenza vaccine (IVACFLU)--each dose with an HA content of 15 mcg from A/California/07/2009 (H1N1)-like virus--will be safe and immunogenic in healthy adults.
Detailed description
This is a phase I, double-blind, individually-randomized (1:1, vaccine:placebo), controlled trial with two groups, IVACFLU (A/H1N1) and placebo. Healthy male and female adults 18 through 40 years of age will be invited to participate. In addition to sponsor monitoring of safety, Program for Appropriate Technology in Health (PATH) will review safety data. Safety data through 7 days post-dose one for all subjects will be reviewed in a blinded fashion prior to administration of dose two of study vaccine or placebo. PATH will review all adverse events (AEs), including clinical laboratory evaluations (pre- and post-vaccination) and will advise if the volunteers may receive dose two of study vaccine or placebo. For all subjects, the procedures and timelines are summarized below.
On the day of first screening (S1), about 14 days (between 5 and 30 days) prior to administration of dose one of study vaccine or placebo, subjects will be screened for eligibility through medical history review, physical examination, testing for serologic evidence of chronic viral infection [human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)], routine biochemical and hematological blood tests and urinalysis by dipstick. For screening for serologic evidence of chronic viral infections, appropriate pre- and post-test counseling must be provided.
Subject screening for eligibility will continue and be completed on the second screening day (S2). This second screening day will occur the same day as scheduled enrollment into the trial and administration of study vaccine or placebo (Day 0). Women will undergo pregnancy tests using urine samples on Day 0. Fully eligible subjects will be enrolled into the trial. At that time, blood specimens will be collected for immunological testing prior to administration of study vaccine or placebo. Subjects will be unaware of which allocation, IVACFLU or placebo, is received; study vaccine and placebo will be masked. Subjects will be carefully monitored for adverse reactions for 60 minutes after vaccination.
During the first week following vaccination, subjects will be asked to record local and general signs and symptoms using preprinted diary cards, thermometer, and small ruler. Concomitant medications will also be recorded. In addition to solicited signs, subjects will be asked to report any other adverse events, whether or not they believe that the event is related to the vaccination. Member of the investigator's clinical team will visit subjects one and five days after vaccination to check that subjects are correctly completing the diary card and to check on the subjects' well-being. Subjects will then return to the study clinic 7 days after dose one. At that time, the investigator will check the subjects' diary cards and transcribe all adverse events onto the case report forms using medical language. Blood and urine specimens will also be collected for routine biochemical and hematological blood tests and urinalysis by dipstick.
Two days before subjects are scheduled to receive dose two, subjects will be visited or called to remind them of the next visit to the study clinic and to check on the subjects' well-being. Subjects will return to the study clinic at 3 weeks after administration of dose one of study vaccine or placebo in order to receive dose two. At that time, interim histories and concomitant medications will be reviewed. Women will again undergo urine pregnancy tests. All subjects will undergo collection of blood and urine specimens for routine biochemical and hematological blood tests and urinalysis by dipstick and collection of blood serum specimens for immunologic analyses. Then subjects will receive dose two of study vaccine or placebo and be monitored for 60 minutes.
After receipt of dose two, subjects will again complete diary cards for 7 days after vaccination with visits by members of the investigator's clinical team again at days one and five after vaccination to check that the subjects are correctly completing diary cards and to check on the subjects' well-being. Subjects will then return to the study clinic 7 days after dose two (Day 28) for review of diary cards by the investigator and collection of blood and urine specimens for routine biochemical and hematological blood tests and urinalysis by dipstick.
Two days before the subjects' next scheduled visit at 3 weeks after administration of dose two, subjects will be visited or called to remind them of the next visit to the study clinic and to check on the subjects' well-being. Subjects will then return to the study clinic at 3 weeks after administration of dose two (Day 42) of study vaccine or placebo for another study visit. At that time, interim histories and concomitant medications will again be reviewed and final blood specimens will be collected for immunogenicity analyses. Women will also undergo a final pregnancy screen.
Subjects will then be asked to immediately report severe adverse events (SAEs) which occur from Day 42 to Day 201 (approximately 6 months after receipt of dose two). To facilitate this reporting, a member of the investigator's team will visit or call the subjects monthly to check on their well-being. At last study visit on Day 201, subjects will be interviewed and examined one last time before completing the study.
For the evaluation of serum antibodies (by hemagglutination inhibition and microneutralization), serum specimens will be collected on Day 0 (prior to administration of dose one of study vaccine or placebo), on Day 21 (prior to administration of dose two of study vaccine or placebo) and on Day 42.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Influenza vaccine | Experimental | Biological: IVACFLUReceived 0.50 mL of inactivated monovalent influenza vaccine (IVACFLU), administered intramuscularly, on days 0 and 21 |
| Placebo | Placebo comparator | Other: PlaceboReceived placebo, administered intramuscularly, on days 0 and 21 |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Male or female adult 18 (age of legal consent in Vietnam) through 40 years of age at the enrollment visit.
- Literate and willing to provide written informed consent.
- Free of obvious health problems, 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, birth control pills, condoms) through the Day 42 visit.
Key exclusion criteria (21 listed)
- 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.)
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 |
|---|---|---|
| IVACFLUAlso: whole virion monovalent A/H1N1 influenza vaccineIVACFLU is a whole virus vaccine, collected in a linear sucrose density gradient solution using a continuous flow centrifuge Alfpa Wassmann and inactivated with formaldehyde. It was formulated to contain 15 mcg hemagglutinin (HA) of influenza A/California/07/2009(H1N1)-like virus per 0.5 mL dose and filled in single dose vials. | Biological | Influenza vaccine |
| PlaceboPhosphate buffered saline (PBS), pH 7.2, in 0.5 ml single-dose vials. | Other | Placebo |
Primary outcome
Number of Participants With Maximum Systemic Reaction After Vaccination 1
Time frame: 7 days
Systemic and local reactogenicity data were collected on Study Days 0, 7, 21 and 28, prevaccination, and within 60 minutes post-vaccination by clinic staff. Subjects completed diary cards for 7 days after each vaccination and received visits from the investigator's clinical team at Days 1 and 5 following each vaccination. Solicited systemic reactogenicity events included body temperature, feverishness, chills, cough, difficulty breathing, runny nose, nasal congestion, sore throat, hoarseness of voice, headache, confusion, convulsions/seizures, fatigue/malaise, muscle aches, joint pain, pink or red eyes, sore eyes, itchy eyes, drainage from eyes, ear pain or discharge, rash, abdominal pain, diarrhea, vomiting and jaundice. Solicited local reactogenicity included size of redness, size of swelling, size of induration, pain, and tenderness.
Number of Participants With Maximum Systemic Reaction After Vaccination 2
Time frame: 7 days
Systemic and local reactogenicity data were collected on Study Days 0, 7, 21 and 28, prevaccination, and within 60 minutes post-vaccination by clinic staff. Subjects completed diary cards for 7 days after each vaccination and received visits from the investigator's clinical team at Days 1 and 5 following each vaccination. Solicited systemic reactogenicity events included body temperature, feverishness, chills, cough, difficulty breathing, runny nose, nasal congestion, sore throat, hoarseness of voice, headache, confusion, convulsions/seizures, fatigue/malaise, muscle aches, joint pain, pink or red eyes, sore eyes, itchy eyes, drainage from eyes, ear pain or discharge, rash, abdominal pain, diarrhea, vomiting and jaundice. Solicited local reactogenicity included size of redness, size of swelling, size of induration, pain, and tenderness.
Number of Participants With Maximum Local Reaction After Vaccination 1
Time frame: 7 days
Systemic and local reactogenicity data were collected on Study Days 0, 7, 21 and 28, prevaccination, and within 60 minutes post-vaccination by clinic staff. Subjects completed diary cards for 7 days after each vaccination and received visits from the investigator's clinical team at Days 1 and 5 following each vaccination. Solicited local reactogenicity included size of redness, size of swelling, size of induration, pain, and tenderness.
Number of Participants With Maximum Local Reaction After Vaccination 2
Time frame: 7 days
Systemic and local reactogenicity data were collected on Study Days 0, 7, 21 and 28, prevaccination, and within 60 minutes post-vaccination by clinic staff. Subjects completed diary cards for 7 days after each vaccination and received visits from the investigator's clinical team at Days 1 and 5 following each vaccination. Solicited local reactogenicity included size of redness, size of swelling, size of induration, pain, and tenderness.
Unsolicited, Non-serious Adverse Events
Time frame: 7 days after each dose (Day 7 and Day 28)
Subjects completed diary cards for 7 days after each vaccination and received visits from the investigator's clinical team at Days 1 and 5 following each vaccination. Adverse events were collected throughout the study period, and were graded for severity; however unsolicited adverse events were assessed only for relationship to vaccine if the events were immediate reactions or considered to be serious adverse events.
12 secondary outcomes
Geometric Mean Titer of Hemagglutination-inhibition Antibodies (HAI)
Time frame: Day 0, Day 21 and Day 42
Ratio of Geometric Mean Titer of Hemagglutination-inhibition Antibodies (HAI)
Time frame: Day 0, Day 21 and Day 42
Number and Percentage of All Subjects Achieving a Four-fold Rise in Hemagglutination-inhibition Antibodies (HAI)
Time frame: Day 21 and Day 42
Number and Percentage of Subjects Achieving a Four-fold Rise in Hemagglutination-inhibition Antibodies (HAI) Among Subjects With Baseline Titer Less Than 40
Time frame: Day 21 and Day 42
Number and Percentage of Subjects Achieving a Four-fold Rise in Hemagglutination-inhibition Antibodies (HAI) Among Subjects With Baseline Titer Greater Than 40
Time frame: Day 21 and Day 42
Number and Percentage of Subjects Developing a Seroprotective Hemagglutination-inhibition (HAI) Antibody Titer
Time frame: Day 21 and Day 42
Geometric Mean Titer of Microneutralizing (MN) Antibodies
Time frame: Day 0, Day 21 and Day 42
Ratio of Geometric Mean Titer of Microneutralization (MN) Antibodies
Time frame: Day 0, Day 21 and Day 42
Number and Percentage of All Subjects Achieving a Four-fold Rise in Microneutralization (MN) Antibodies
Time frame: Day 21 and Day 42
Number and Percentage of Subjects Achieving a Four-fold Rise in Microneutralizing (MN) Antibodies Among Subjects With Baseline Titer Less Than 40
Time frame: Day 21 and Day 42
Number and Percentage of Subjects Achieving a Four-fold Rise in Microneutralizing (MN) Antibodies Among Subjects With Baseline Titer Greater Than 40
Time frame: Day 21 and Day 42
Number and Percentage of Subjects Developing a Seroprotective Microneutralizing (MN) Antibody Titer
Time frame: Day 21 and Day 42
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30337172Thang HV, Huong VM, Victor JC, Van CB, Nga NT, Be LV, Cuong NP, Tsvetnitsky V, Neuzil KM, Power M, Flores J. Safety and immunogenicity of inactivated monovalent influenza A/H1N1 vaccine candidate manufactured in Vietnam. Vaccine. 2018 Nov 12;36(46):6918-6925. doi: 10.1016/j.vaccine.2018.10.013. Epub 2018 Oct 15.
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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.
Kathleen M Neuzil, MD, MPH study director
PATH
Le V Be, MD, PhD study director
Institute of Vaccines and Medical Biologicals, Vietnam
Ho V Thang, MD, MSc principal investigator
Pasteur Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IVACFLU in people with Influenza, run by PATH at 1 site 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 5 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 27 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 27 Feb 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 of Participants With Maximum Systemic Reaction After Vaccination 1 (time frame: 7 days). The study lists 5 primary outcomes in all. 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 NCT01507779, 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 27 Feb 2019.