InfluenzaPhase 1/2NCT01010737
A Double-Dose Safety Study of An Influenza Vaccine (Multimeric-001) Injected to Elderly Volunteers
A Phase 1/2 study testing Multimeric-001 250 mcg, Adjuvanted Multimeric-001 250mcg and Adjuvant: Montonide isa 51 VG in people with Influenza, run by BiondVax Pharmaceuticals ltd. at 1 site in Israel.
Trial summary
This is a phase I/II, randomized, single-blind, placebo-controlled escalating double-dose study of the safety and priming potential of an intramuscular Influenza vaccine (Multimeric-001) injected to elderly volunteers. Read more about this study
- Who is it for?
- Ages 55 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Multimeric-001 250 mcg, Adjuvanted Multimeric-001 250mcg and Adjuvant: Montonide isa 51 VG
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteIsrael
- Study dates
- Sep 2009to Mar 2010
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 55 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males and females between the age of 55 and 75 years (inclusive):
- Healthy or treated for any or all of the following conditions:
- Hypertension, under control with standard medications
- Hyperlipidemia, medically treated
- Subjects who provide written informed consent to participate in the study.
- Subjects able to adhere to the visit schedule and protocol requirements and be available to complete the study.
- Haematology, chemistry and urinalysis values with no clinical significance or do not reflect a medical condition which, according to the physician's judgment, might confound the results of the study or pose additional risk to the subject by participation in the study.
- Female of childbearing age must agree to use an acceptable method of contraception and male subjects should use a condom throughout the study period (including the follow up- where applicable) if female partner is not using an effective contraceptive method.
Who cannot join
- Known history of significant medical disorder, which in the investigator's judgment, might confound the results of the study or pose additional risk to the subject by participation in the study.
- Renal dysfunction.
- COPD.
- Chronic cardiovascular system disorders (except hypertension adequately controlled by standard medications).
- Asthma
- Diabetes mellitus.
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- Subjects with known Guillain Barré Syndrome in the past.
- Two or more hospitalizations within the last year prior to screening visit.
- Bleeding disorders including hemophilia or thrombocytopenia, or treatment with anticoagulant therapy (risk of bleeding with intramuscular injection).
- Immunocompromised patients and those receiving concomitant immunosuppressive therapy; or other immune modulating drugs including chronic steroid treatment.
- Subjects who have been immunized with anti-influenza vaccine or infected by influenza virus within eight months prior to the screening visit.
- Administration of any vaccine 30 days before the screening visit.
- Known hypersensitivity to previous influenza vaccination.
- Use of an influenza antiviral medication within 4 weeks of vaccination.
- Known hypersensitivity and/or allergy to any drug or vaccine.
- Known hypersensitivity to egg proteins (eggs or egg products), chicken proteins, or any of the vaccine components, in particular, neomycin, formaldehyde, and octoxinol 9,
- Known history of drug or alcohol abuse.
- Any clinically significant abnormality upon physical examination or in the clinical laboratory tests at screening visit which, according to the physician's judgment, might confound the results of the study or pose additional risk to the subject by participation in the study.
- Increased liver enzymes more than 2.5 times above the upper reference level.
- Positive serology for HIV, HCV antibody or HBsAg.
- Any acute medical situation (e.g. acute infection, ongoing flu symptoms) with or without fever within 48 hours of vaccination, which is considered of significance by the Principal Investigator.
- Pregnant or lactating women at entry to study and those who are unwilling to agree to continue to use acceptable methods of contraception for two months after completion of the study (if applicable).
- Positive blood pregnancy test on screening.
- Subjects who participated in another clinical study within 30 days prior to study entry.
- Subjects who are non-cooperative or unwilling to sign consent form.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II, Randomized, Single-Blind, Placebo-Controlled Escalating Double-Dose, Safety and Priming Potential Study of an Intramuscular Influenza Vaccine (Multimeric-001) Injected to Elderly Volunteers
This is a phase I/II, randomized, single-blind, placebo-controlled escalating double-dose study of the safety and priming potential of an intramuscular Influenza vaccine (Multimeric-001) injected to elderly volunteers.
Read the detailed description
This is a Phase I/II single-center, randomized, placebo-controlled, single-blind, dose-escalation, double-dose administration study comprising two dosing cohorts (Cohort 1: 250 mcg M-001 per injection and Cohort 2: 500 mcg M-001 per injection) with 20 subjects in each cohort receiving either adjuvanted or non-adjuvanted formulations. The adjuvant used was Montanide ISA VG51. Cohort 3 with 20 subjects was administered placebo. After priming with M-001 or placebo, all participants were administered a boost of a conventional trivalent vaccine on day 42.
There was a minimum of 10 days interval between last dosing of the first injection to the last subject of the 250 μg cohort (Cohort 1) and first dosing of the first subject injection with 500 µg cohort (Cohort 2).
For each subject, the second injection was performed 21+2 days after his/her first injection, provided they were deemed fit to be dosed by a study physician.
The DSMB reviewed the safety data obtained from cohorts 1 and 2 before approving their second injection and before dose escalation.
- Conditions
- Influenza
- Being tested
- Multimeric-001 250 mcg, Adjuvanted Multimeric-001 250mcg, Placebo, Adjuvant: Montonide isa 51 VG, Multimeric-001 500 mcg
- Keywords
- Multimeric, Vaccine, Influenza, elderly, phase 1/2, safety, efficacy, tolerability, reactogenicity, Montanide, hemagglutinin inhibition, HAI, TIV
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multimeric-001 250 mcgBiological
Multimeric-001 (M-001) was administered twice at a dose of 250mcg via the IM route to 10 participants as a primer, followed by TIV boost immunization. in 19-23 days interval between them.
Adjuvanted Multimeric-001 250mcgBiological
Injection of Multimeric-001 250 mcg with Adjuvant Montonide isa 51 VG, 2 doses with interval of 19-23 days between them
PlaceboBiological
Placebo injected with PBS (Phosphate Buffered Saline), 2 injections with the interval of 19-23 days between them.
Adjuvant: Montonide isa 51 VGBiological
Injection of Placebo with Adjuvant Montonide isa 51 VG, 2 injections with the interval of 19-23 days between them.
Multimeric-001 500 mcgBiological
Injection of Multimeric-001 with PBS, 2 injections with the interval of 19-23 days between them.
Adjuvanted Multimeric-001 500mcgBiological
Injection of Multimeric-001 500 mcg with Adjuvant Montonide isa 51 VG, 2 doses with the interval of 19-23 days between them
TIVBiological
Also called Vaxigrip
Injection of the conventional flu vaccine: Vaxigrip to all study participants.
| Study group | Role | What they receive |
|---|---|---|
| Multimeric-001 250 mcg | Experimental | 250mcg of Multimeric-001 was administered twice at an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered. Receives: Biological: Multimeric-001 250 mcg; Biological: TIV |
| Adjuvant: Montonide isa 51 VG | Active comparator | Adjuvanted PBS was administered twice with a 19-23 day interval via the IM route to 10 participants and then a TIV boost was administered. Receives: Biological: Adjuvant: Montonide isa 51 VG; Biological: TIV |
| Placebo | Active comparator | PBS was administered twice with a 19-23 day interval via the IM route to 10 participants and then a TIV boost was administered. Receives: Biological: Adjuvant: Montonide isa 51 VG; Biological: TIV |
| Multimeric-001 500 mcg | Experimental | 500mcg of M-001 was administered twice with an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered. Receives: Biological: Adjuvanted Multimeric-001 500mcg; Biological: TIV |
| Adjuvanted Multimeric-001 500mcg | Experimental | 5000mcg of Adjuvanted M-001 was administered twice with an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered. Receives: Biological: Adjuvanted Multimeric-001 250mcg; Biological: TIV |
| Adjuvanted Multimeric-001 250mcg | Experimental | 250mcg of Adjuvanted M-001 was administered twice with an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered. Receives: Biological: Placebo; Biological: Multimeric-001 500 mcg; Biological: TIV |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety, local and systemic tolerability and reactogenicity of Multimeric-001 vaccine when administered intramuscularly twice to elderly male and female subjects, using chemistry, CBC, fibrinogen, and urinalysis measurements.
The Multimeric-001 vaccine exhibits a positive safety profile. The number of subjects reporting adverse events (AEs) after treatment with active vaccines was similar to respective placebo cohorts. Overall AE frequencies for each active group were similar to those of placebo counterparts.
Measured: From day 0 until termination visit
Secondary outcomes (4)
To characterize the immune response
The Multimeric-001 vaccine induces both humoral and cellular immune responses, confirming previous findings in younger adults.
Measured: 21 days after second immunization with M-001 and 21 days after TIV boost
To monitor cellular immune responses
PBMC proliferation associated with IFN gamma secretion was detected after prime immunizations following in vitro exposure of the cells to M-001 or influenza viruses.
Measured: 21 days after second M-001 immunization
To obtain preliminary data on the contribution of the adjuvant
Adjuvant had an impact on anti-M-001 IgG levels but not on HAI antibody levels.
Measured: 21 days after second M-001 immunization and 21 days after TIV boost
To obtain preliminary evidence about the efficacy of M-001 as a primer
The prime-boost regimen elicits HAI immune responses, which enables assessment of an accepted surrogate marker considered to correlate with influenza vaccine activity.Priming with M-001 before a TIV boost resulted in a greater proportion of subjects seroconverted to TIV and non-TIV strains as compared to subjects given TIV alone.
Measured: 21 days after TIV boost
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2009 (estimated)
- Study startSep 2009
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- BiondVax Pharmaceuticals ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jacob Atsmon, MD, Principal investigator, CRC, Sourascky MC, Israel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01010737
- Sponsor's protocol ID
- BVX-003
- Status last verified
- Jul 2012
- First submitted
- 18 Oct 2009
- Last updated
- 31 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Randomized, Single-Blind, Placebo-Controlled Escalating Double-Dose, Safety and Priming Potential Study of an Intramuscular Influenza Vaccine (Multimeric-001) Injected to Elderly Volunteers
- ClinicalTrials.gov ID
- NCT01010737
- Acronym / sponsor ID
- BVX-003
- Conditions
- Influenza
- Keywords
- Multimeric, Vaccine, Influenza, elderly, phase 1/2, safety, efficacy, tolerability
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- BiondVax Pharmaceuticals ltd.Industry (pharma, biotech, devices)
- Study start
- Sep 2009
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 10 Nov 2009 (estimated)
- Results
- Not posted in the source record
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/II, randomized, single-blind, placebo-controlled escalating double-dose study of the safety and priming potential of an intramuscular Influenza vaccine (Multimeric-001) injected to elderly volunteers.
Detailed description
This is a Phase I/II single-center, randomized, placebo-controlled, single-blind, dose-escalation, double-dose administration study comprising two dosing cohorts (Cohort 1: 250 mcg M-001 per injection and Cohort 2: 500 mcg M-001 per injection) with 20 subjects in each cohort receiving either adjuvanted or non-adjuvanted formulations. The adjuvant used was Montanide ISA VG51. Cohort 3 with 20 subjects was administered placebo. After priming with M-001 or placebo, all participants were administered a boost of a conventional trivalent vaccine on day 42.
There was a minimum of 10 days interval between last dosing of the first injection to the last subject of the 250 μg cohort (Cohort 1) and first dosing of the first subject injection with 500 µg cohort (Cohort 2).
For each subject, the second injection was performed 21+2 days after his/her first injection, provided they were deemed fit to be dosed by a study physician.
The DSMB reviewed the safety data obtained from cohorts 1 and 2 before approving their second injection and before dose escalation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Multimeric-001 250 mcg | Experimental | Biological: Multimeric-001 250 mcg, Biological: TIV250mcg of Multimeric-001 was administered twice at an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered. |
| Adjuvant: Montonide isa 51 VG | Active comparator | Biological: Adjuvant: Montonide isa 51 VG, Biological: TIVAdjuvanted PBS was administered twice with a 19-23 day interval via the IM route to 10 participants and then a TIV boost was administered. |
| Placebo | Active comparator | Biological: Adjuvant: Montonide isa 51 VG, Biological: TIVPBS was administered twice with a 19-23 day interval via the IM route to 10 participants and then a TIV boost was administered. |
| Multimeric-001 500 mcg | Experimental | Biological: Adjuvanted Multimeric-001 500mcg, Biological: TIV500mcg of M-001 was administered twice with an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered. |
| Adjuvanted Multimeric-001 500mcg | Experimental | Biological: Adjuvanted Multimeric-001 250mcg, Biological: TIV5000mcg of Adjuvanted M-001 was administered twice with an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered. |
| Adjuvanted Multimeric-001 250mcg | Experimental | Biological: Placebo, Biological: Multimeric-001 500 mcg, Biological: TIV250mcg of Adjuvanted M-001 was administered twice with an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered. |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males and females between the age of 55 and 75 years (inclusive):
- Subjects who provide written informed consent to participate in the study.
- Subjects able to adhere to the visit schedule and protocol requirements and be available to complete the study.
- Haematology, chemistry and urinalysis values with no clinical significance or do not reflect a medical condition which, according to the physician's judgment, might confound the results of the study or pose additional risk to the subject by participation in the study.
- Female of childbearing age must agree to use an acceptable method of contraception and male subjects should use a condom throughout the study period (including the follow up- where applicable) if female partner is not using an effective contraceptive method.
Key exclusion criteria (25 listed)
- Known history of significant medical disorder, which in the investigator's judgment, might confound the results of the study or pose additional risk to the subject by participation in the study.
- Renal dysfunction.
- COPD.
- Chronic cardiovascular system disorders (except hypertension adequately controlled by standard medications).
- Asthma
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 |
|---|---|---|
| Multimeric-001 250 mcgMultimeric-001 (M-001) was administered twice at a dose of 250mcg via the IM route to 10 participants as a primer, followed by TIV boost immunization. in 19-23 days interval between them. | Biological | Multimeric-001 250 mcg |
| Adjuvanted Multimeric-001 250mcgInjection of Multimeric-001 250 mcg with Adjuvant Montonide isa 51 VG, 2 doses with interval of 19-23 days between them | Biological | Adjuvanted Multimeric-001 500mcg |
| PlaceboPlacebo injected with PBS (Phosphate Buffered Saline), 2 injections with the interval of 19-23 days between them. | Biological | Adjuvanted Multimeric-001 250mcg |
| Adjuvant: Montonide isa 51 VGInjection of Placebo with Adjuvant Montonide isa 51 VG, 2 injections with the interval of 19-23 days between them. | Biological | Adjuvant: Montonide isa 51 VG, Placebo |
| Multimeric-001 500 mcgInjection of Multimeric-001 with PBS, 2 injections with the interval of 19-23 days between them. | Biological | Adjuvanted Multimeric-001 250mcg |
| Adjuvanted Multimeric-001 500mcgInjection of Multimeric-001 500 mcg with Adjuvant Montonide isa 51 VG, 2 doses with the interval of 19-23 days between them | Biological | Multimeric-001 500 mcg |
| TIVAlso: VaxigripInjection of the conventional flu vaccine: Vaxigrip to all study participants. | Biological | Adjuvant: Montonide isa 51 VG, Adjuvanted Multimeric-001 250mcg, Adjuvanted Multimeric-001 500mcg, Multimeric-001 250 mcg, Multimeric-001 500 mcg, Placebo |
Primary outcome
To assess the safety, local and systemic tolerability and reactogenicity of Multimeric-001 vaccine when administered intramuscularly twice to elderly male and female subjects, using chemistry, CBC, fibrinogen, and urinalysis measurements.
Time frame: From day 0 until termination visit
The Multimeric-001 vaccine exhibits a positive safety profile. The number of subjects reporting adverse events (AEs) after treatment with active vaccines was similar to respective placebo cohorts. Overall AE frequencies for each active group were similar to those of placebo counterparts.
4 secondary outcomes
To characterize the immune response
Time frame: 21 days after second immunization with M-001 and 21 days after TIV boost
To monitor cellular immune responses
Time frame: 21 days after second M-001 immunization
To obtain preliminary data on the contribution of the adjuvant
Time frame: 21 days after second M-001 immunization and 21 days after TIV boost
To obtain preliminary evidence about the efficacy of M-001 as a primer
Time frame: 21 days after TIV boost
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2012.
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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.
Jacob Atsmon, MD principal investigator
CRC, Sourascky MC, Israel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Multimeric-001 250 mcg, Adjuvanted Multimeric-001 250mcg and Adjuvant: Montonide isa 51 VG in people with Influenza, run by BiondVax Pharmaceuticals ltd. at 1 site in Israel.
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 8 inclusion and 25 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 31 Jul 2012. 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 Israel. 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. 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 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To assess the safety, local and systemic tolerability and reactogenicity of Multimeric-001 vaccine when administered intramuscularly twice to elderly male and female subjects, using chemistry, CBC, fibrinogen, and urinalysis measurements. (time frame: From day 0 until termination visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jul 2012.