Influenza, HumanPhase 1NCT02585700
A Study of a Seasonal Trivalent Split, Inactivated Influenza Vaccine
A Phase 1 study testing Influenza vaccine, split inactivated in people with Influenza, Human, run by Institute of Virology, Vaccines and Sera, Torlak at 1 site in Serbia.
Trial summary
This is a phase I, double-blind, randomized, placebo-controlled trial with two groups of participants to receive seasonal trivalent split, inactivated influenza vaccine (A/H1N1; A/H3N2 and B) or placebo (phosphate buffered saline). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Human
- What is being tested?
- Influenza vaccine, split inactivated
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteSerbia
- Study dates
- Nov 2015to Mar 2016
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female adult 18 through 45 years of age at the enrollment visit.
- Literate (by self-report) and willing to provide written informed consent.
- Healthy, as established by the medical history, physical examination, and screening laboratory evaluations.
- Capable and willing to complete Memory Aids and willing to return for all follow-up visits.
- For females, willing to utilize reliable birth control measures (e.g., intrauterine device, hormonal contraception, condoms) from Day 0 through the Day 21 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 4 weeks prior to enrollment or refusal to postpone receipt of such vaccines until after the Day 21 visit.
- Current or recent (within 2 weeks of vaccination) acute illness with or without fever.
- Receipt of immune globulin or other blood products within 3 months prior to study enrollment or planned receipt of such products prior to the Day 21 visit.
- Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study vaccination. (For corticosteroids, this means prednisone or equivalent, equal or more than 0.5 mg per kg per day; topical steroids are allowed.)
- History of asthma.
Show all 20Show fewer
- Hypersensitivity after previous administration of any vaccine.
- Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein.
- Acute or chronic clinically significant pulmonary, cardiovascular, hepatobiliary, metabolic, neurologic, psychiatric or renal functional abnormality, as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives.
- History of any blood or solid organ cancer.
- History of thrombocytopenic purpura or known bleeding disorder.
- History of seizures.
- Known or suspected immunosuppressed or immunodeficient condition of any kind.
- Confirmed hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Known HIV infection (self-report).
- Known active tuberculosis or symptoms of active tuberculosis, regardless of cause (self-report).
- History of chronic alcohol abuse and/or illegal drug use.
- Pregnancy or lactation. (A negative pregnancy test will be required before administration of study product for all women of childbearing potential.)
- History of Guillain-Barré Syndrome
- Any condition that, in the opinion of the investigator, would increase the health risk to the subject if he/she participates in the study or would interfere with the evaluation of the study objectives.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Double Blinded, Randomized, Placebo-Controlled Study to Examine the Safety and Immunogenicity of a Seasonal Trivalent Split, Inactivated Influenza Vaccine Produced by Torlak in Healthy Adult Volunteers in Serbia
This is a phase I, double-blind, randomized, placebo-controlled trial with two groups of participants to receive seasonal trivalent split, inactivated influenza vaccine (A/H1N1; A/H3N2 and B) or placebo (phosphate buffered saline). A total of 60 healthy male and female adults 18 through 45 years of age will be randomized to receive vaccine (30) or placebo (30).
Read the detailed description
This is a phase 1, double blinded, randomized, placebo-controlled study. The study will be conducted at 1 site in Serbia. Sixty (60) healthy male and female adults, 18 to 45 years of age, will be enrolled into the trial. Subjects will be randomized 1:1 to one of two treatment allocations: 30 to vaccine, 30 to placebo. The study will utilize a "randomized block design" to assure a balance of 1:1 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. The study should take about 5 months to complete, with each subject involved for 3 months from the day of injection. The justification for the 3 month follow up, rather than 6 month follow up is that this is an inactivated vaccine that follows very standard manufacturing practices with standard antigens. The safety of inactivated influenza vaccines is well-established. Adding length to the follow up results in delays in future testing of the vaccine for licensure.
- Conditions
- Influenza, Human
- Being tested
- Influenza vaccine, split inactivated, Placebo
- Keywords
- Grippe, Human Flu, Human influenza
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Influenza vaccine, split inactivatedBiological
Seasonal trivalent inactivated influenza vaccine (TIV), inactivated split virion, purified by sucrose gradient ultracentrifugation. The vaccine is produced in hen's eggs, and inactivated with beta-propiolactone.
PlaceboOther
0.5 mL of phosphate buffered saline
| Study group | Role | What they receive |
|---|---|---|
| Vaccine | Experimental | 0.5 mL of influenza vaccine, split, inactivated with 15 mcg of haemagglutination (HA) of each of 3 strains:
* NYMC BX-51B reassortant of B/Massachusetts/2/2012
* X-181 reassortant of H1/A/California/7/2009
* X-223A reassortant of H3/A/Texas/50/2012. Receives: Biological: Influenza vaccine, split inactivated |
| Placebo | Placebo comparator | 0.5 mL of phosphate buffered saline Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Immediate Adverse Events
Number of subjects with observed immediate adverse events, including allergic reaction or anaphylaxis, following administration of the study product.
Measured: 30-minute post-vaccination period.
Number and Percentage of Subjects With Solicited Local Reactogenicity
Number of subjects reporting solicited local reactions (redness, swelling, induration, pain and tenderness) at the injection site post-vaccination with study vaccine or placebo
Measured: 7-day period (Days 0-6) post-vaccination.
Number and Percentage of Subjects With Solicited Systemic Reactogenicity
Number of subjects reporting solicited systemic reactions (fever, fatigue/malaise, muscle aches, joint aches, chills, nausea, vomiting, and headache) post-vaccination with study vaccine or Placebo
Measured: 7-day period (Days 0-6) post-vaccination.
Number and Percentage of Subjects With Occurrence of Unsolicited Adverse Events
These data are presented broadly as number per group for the study. Please see AE reporting section for more specific details on AEs.
Measured: Within 21 days post vaccination
Number and Percentage of Subjects With Occurrence of Serious Adverse Events (SAE)
Measured: Over the entire study period (Day 90).
Secondary outcomes (6)
Number and Percentage of Seroconverted Subjects Against 3 Strains of Influenza Vaccine.
Seroconversion is defined as a serum HAI titer meeting the following criteria:
- pre-vaccination titer <1:10 and a post-vaccination titer ≥ 1:40 or
- pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination measured on Day 21.
The 3 influenza strains assessed were B/Massachusetts, H1/A/California and H3/A/Texas
Measured: Day 21
Number and Percentage of Seroprotected Subjects Against 3 Strains of Influenza Vaccine
A seroprotected subject was defined as a vaccinated subject who had a serum Hemagluttination Inhibition (HAI) titer ≥ 1:40. The 3 influenza strains assessed were B/Massachusetts, H1/A/California an d H3/A/Texas
Measured: Day 0 and Day 21 post vaccination
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens
The 3 influenza strains assessed were B/Massachusetts, H1/A/California an d H3/A/Texas
Measured: Pre- (Day 0) and post-vaccination (Day 21)
Geometric Mean Fold Rises (GMFRs) of Serum (HAI) Antibodies (Post-vaccination / Pre-vaccination) for Each of the 3 Antigens.
The 3 influenza strains assessed were B/Massachusetts, H1/A/California an d H3/A/Texas
Measured: Pre- (Day 0) and post-vaccination (Day 21)
Geometric Mean Neutralization Titers of Neutralizing Antibodies (MNT) Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens.
Measured: Pre- (Day 0) and post-vaccination (Day 21)
Geometric Mean Fold Rises (GMFRs) of MNT (Post-vaccination / Pre-vaccination) for Each of the 3 Antigens.
The 3 influenza strains assessed were B/Massachusetts, H1/A/California an d H3/A/Texas
Measured: Pre- (Day 0) and post-vaccination (Day 21)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2015 (estimated)
- Study startNov 2015
- Primary completionMar 2016
- Study completionMar 2016
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 Influenza, HumanStudies 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
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Virology, Vaccines and Sera, Torlak
- Sponsor type
- University, hospital or other
- Collaborators
- Department of Health and Human Services, World Health Organization, PATH, Comac Medical
- Responsible party
- Sponsor
- Investigators
- Goran Stevanovic, PhD, Principal investigator, Clinic for Infectious and Tropical Diseases
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02585700
- Sponsor's protocol ID
- TORLAK-100
- Status last verified
- Oct 2015
- First submitted
- 13 Oct 2015
- Last updated
- 15 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stevanovic G, Lavadinovic L, Filipovic Vignjevic S, Holt R, Ilic K, Berlanda Scorza F, Sparrow E, Stoiljkovic V, Torelli G, Madenwald T, Socquet M, Barac A, Ilieva-Borisova Y, Pelemis M, Flores J. Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a phase I randomized clinical trial in healthy Serbian adults. Hum Vaccin Immunother. 2018 Mar 4;14(3):579-586. doi: 10.1080/21645515.2017.1415683. Epub 2018 Feb 23.
PubMed 29239682
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Double Blinded, Randomized, Placebo-Controlled Study to Examine the Safety and Immunogenicity of a Seasonal Trivalent Split, Inactivated Influenza Vaccine Produced by Torlak in Healthy Adult Volunteers in Serbia
- ClinicalTrials.gov ID
- NCT02585700
- Acronym / sponsor ID
- TORLAK-100
- Conditions
- Influenza, Human
- Keywords
- Grippe, Human Flu, Human influenza
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Institute of Virology, Vaccines and Sera, TorlakUniversity, hospital or other
- Collaborators
- Department of Health and Human Services, World Health Organization, PATH, Comac Medical
- Study start
- Nov 2015
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 23 Oct 2015 (estimated)
- Results
- Posted 15 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I, double-blind, randomized, placebo-controlled trial with two groups of participants to receive seasonal trivalent split, inactivated influenza vaccine (A/H1N1; A/H3N2 and B) or placebo (phosphate buffered saline). A total of 60 healthy male and female adults 18 through 45 years of age will be randomized to receive vaccine (30) or placebo (30).
Detailed description
This is a phase 1, double blinded, randomized, placebo-controlled study. The study will be conducted at 1 site in Serbia. Sixty (60) healthy male and female adults, 18 to 45 years of age, will be enrolled into the trial. Subjects will be randomized 1:1 to one of two treatment allocations: 30 to vaccine, 30 to placebo. The study will utilize a "randomized block design" to assure a balance of 1:1 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. The study should take about 5 months to complete, with each subject involved for 3 months from the day of injection. The justification for the 3 month follow up, rather than 6 month follow up is that this is an inactivated vaccine that follows very standard manufacturing practices with standard antigens. The safety of inactivated influenza vaccines is well-established. Adding length to the follow up results in delays in future testing of the vaccine for licensure.
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 |
|---|---|---|
| Vaccine | Experimental | Biological: Influenza vaccine, split inactivated0.5 mL of influenza vaccine, split, inactivated with 15 mcg of haemagglutination (HA) of each of 3 strains: * NYMC BX-51B reassortant of B/Massachusetts/2/2012 * X-181 reassortant of H1/A/California/7/2009 * X-223A reassortant of H3/A/Texas/50/2012. |
| Placebo | Placebo comparator | Other: Placebo0.5 mL of phosphate buffered saline |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy male or female adult 18 through 45 years of age at the enrollment visit.
- Literate (by self-report) and willing to provide written informed consent.
- Healthy, as established by the medical history, physical examination, and screening laboratory evaluations.
- Capable and willing to complete Memory Aids and willing to return for all follow-up visits.
- For females, willing to utilize reliable birth control measures (e.g., intrauterine device, hormonal contraception, condoms) from Day 0 through the Day 21 visit.
Key exclusion criteria (20 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 4 weeks prior to enrollment or refusal to postpone receipt of such vaccines until after the Day 21 visit.
- Current or recent (within 2 weeks of vaccination) acute illness with or without fever.
- Receipt of immune globulin or other blood products within 3 months prior to study enrollment or planned receipt of such products prior to the Day 21 visit.
- Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study vaccination. (For corticosteroids, this means prednisone or equivalent, equal or more than 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 |
|---|---|---|
| Influenza vaccine, split inactivatedSeasonal trivalent inactivated influenza vaccine (TIV), inactivated split virion, purified by sucrose gradient ultracentrifugation. The vaccine is produced in hen's eggs, and inactivated with beta-propiolactone. | Biological | Vaccine |
| Placebo0.5 mL of phosphate buffered saline | Other | Placebo |
Primary outcome
Number of Subjects With Immediate Adverse Events
Time frame: 30-minute post-vaccination period.
Number of subjects with observed immediate adverse events, including allergic reaction or anaphylaxis, following administration of the study product.
Number and Percentage of Subjects With Solicited Local Reactogenicity
Time frame: 7-day period (Days 0-6) post-vaccination.
Number of subjects reporting solicited local reactions (redness, swelling, induration, pain and tenderness) at the injection site post-vaccination with study vaccine or placebo
Number and Percentage of Subjects With Solicited Systemic Reactogenicity
Time frame: 7-day period (Days 0-6) post-vaccination.
Number of subjects reporting solicited systemic reactions (fever, fatigue/malaise, muscle aches, joint aches, chills, nausea, vomiting, and headache) post-vaccination with study vaccine or Placebo
Number and Percentage of Subjects With Occurrence of Unsolicited Adverse Events
Time frame: Within 21 days post vaccination
These data are presented broadly as number per group for the study. Please see AE reporting section for more specific details on AEs.
Number and Percentage of Subjects With Occurrence of Serious Adverse Events (SAE)
Time frame: Over the entire study period (Day 90).
6 secondary outcomes
Number and Percentage of Seroconverted Subjects Against 3 Strains of Influenza Vaccine.
Time frame: Day 21
Number and Percentage of Seroprotected Subjects Against 3 Strains of Influenza Vaccine
Time frame: Day 0 and Day 21 post vaccination
Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens
Time frame: Pre- (Day 0) and post-vaccination (Day 21)
Geometric Mean Fold Rises (GMFRs) of Serum (HAI) Antibodies (Post-vaccination / Pre-vaccination) for Each of the 3 Antigens.
Time frame: Pre- (Day 0) and post-vaccination (Day 21)
Geometric Mean Neutralization Titers of Neutralizing Antibodies (MNT) Pre- (Day 0) and Post-vaccination (Day 21) for Each of the 3 Antigens.
Time frame: Pre- (Day 0) and post-vaccination (Day 21)
Geometric Mean Fold Rises (GMFRs) of MNT (Post-vaccination / Pre-vaccination) for Each of the 3 Antigens.
Time frame: Pre- (Day 0) and post-vaccination (Day 21)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29239682Stevanovic G, Lavadinovic L, Filipovic Vignjevic S, Holt R, Ilic K, Berlanda Scorza F, Sparrow E, Stoiljkovic V, Torelli G, Madenwald T, Socquet M, Barac A, Ilieva-Borisova Y, Pelemis M, Flores J. Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a phase I randomized clinical trial in healthy Serbian adults. Hum Vaccin Immunother. 2018 Mar 4;14(3):579-586. doi: 10.1080/21645515.2017.1415683. Epub 2018 Feb 23.
- 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.
Goran Stevanovic, PhD principal investigator
Clinic for Infectious and Tropical Diseases
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 Influenza vaccine, split inactivated in people with Influenza, Human, run by Institute of Virology, Vaccines and Sera, Torlak at 1 site in Serbia.
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 20 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 15 Jan 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 Serbia. 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 15 Jan 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 Subjects With Immediate Adverse Events (time frame: 30-minute post-vaccination period.). 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 NCT02585700, 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 15 Jan 2019.