Influenza
Conditions
Keywords
Influenza, vaccine, universal, M-001, Multimeric-001, Flu
Brief summary
The pivotal Phase 3 trial plans to enroll a total of approximately 12,460 participants aged 50+ over two years. Participants will be immunized twice with the M-001 universal influenza vaccine candidate or placebo and then followed for up to 2 seasons. The trial will evaluate the number of influenza cases in each group and the severity of illness during the follow up period.
Detailed description
The placebo-controlled pivotal clinical efficacy Phase 3 trial plans to enroll a total of approximately 12,460 participants over two years. Participants will be immunized twice with the M-001 influenza vaccine candidate or placebo. Influenza incidence and illness severity will be evaluated throughout the follow-up period of up to two years. Participants will be 50 years and older, with at least half over 65 years of age. The trial is expected to take place in eastern European countries and begin prior to the 2018/19 Northern Hemisphere flu season.
Interventions
BIOLOGICALM-001
A recombinant protein containing 9 conserved epitopes from Influenza A and B that are common to the vast majority of influenza viruses.
BIOLOGICALSaline
0.9% sodium chloride (NaCl)
Sponsors
BiondVax Pharmaceuticals ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All parties are blinded except for the person who prepares the syringe for injection. The M-001 is cloudy white and its appearance is different from the transparent saline that is used for placebo. The person prepares the syringe with an opaque sticker that fully covers the syringe contents. People administering the syringe are not involved or present during syringe preparation, and are thus fully blinded.
Intervention model description
Experimental group: 2 immunizations with M-001 Control group: 2 injection of saline (placebo)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Male and female subjects 50 years of age (inclusive) or older, mentally competent, willing and able to give the written informed consent prior to study entry 2. Able to comply with the trial procedures and be available for all study visits. 3. Medically stable. (Subjects may have underlying chronic conditions such as hypertension, diabetes, ischemic heart disease, or hypothyroidism, as long as their symptoms/signs are controlled. If they are on medication for a condition, the medication dose must have been stable for at least 3 months preceding vaccination). 4. Women of childbearing potential (not surgically sterile or postmenopausal for greater than or equal to one year) and men must agree to practice adequate contraception (barrier or hormone methods or intra uterine device (IUD) for women and a condom for men) throughout the study treatment and for at least up to day 51 (for female) and day 111 (for male) of the trial (i.e. 30 (for female) and 90 (for male) days after the last dose of the IMP) 5. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.
Exclusion criteria
1. History of neurological symptoms or signs, or anaphylactic shock following administration of any vaccine. 2. Known or suspected (or have a high risk of developing) impairment/alteration of immune function (excluding that normally associated with advanced age). 3. Receipt of: a) Immunosuppressive drugs: i) systemic glucocorticoids \>/= 10 mg prednisone per day ii) cytotoxic drugs b) Investigational drugs within 30 days before, or planned during, the study c) Blood products within 3 months before, or planned during, the study d) Influenza vaccine within 6 months before the study) Other vaccines within 30 days before, or planned during, the study 4. Any serious disease such as: cancer, autoimmune disease, advanced arteriosclerotic disease or complicated diabetes mellitus, chronic obstructive pulmonary disease (COPD) that requires oxygen therapy, acute or progressive hepatic disease, acute or progressive renal disease, or congestive heart failure, as judged by the PI. 5. An acute illness, including an axillary temperature greater than 38 Celsius (38ºC), occurred within 1 week before first vaccination 6. Positive positive urine pregnancy test prior to vaccination or women who are breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With qRT-PCR or Culture-confirmed Influenza-like Illness | From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year | Prevention of influenza disease by comparing the occurrence of either qRT-PCR or culture confirmed influenza in the M-001 experimental group vs. placebo caused by any influenza A or B virus in association with a protocol defined Influenza Like Illness. |
| Number of Participants With One or More Serious Adverse Events, New Onset Chronic Illness, and Non-solicited Adverse Events | From Day 0 to end of study completion by participant which coincides with end of flu season in the respective year, an average of 4 months per participant per year | Number of participants with one or more Serious Adverse Events, New Onset Chronic illness, and Non-solicited Adverse Events assessed during one flu season per participant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Culture-confirmed Influenza Incidence | From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year | Occurrence of culture confirmed influenza in the M-001 experimental group vs. placebo caused by any influenza A or B virus in association with a protocol defined Influenza Like Illness. |
| Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza | From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year | Assessed by reduction of severity of either qRT-PCR or culture-confirmed influenza illness by the reduction due to M-001 in the average number of days with respiratory or systemic symptoms during the first laboratory-confirmed influenza illness episode. |
| Number of Participants With Influenza-like Illness Symptoms | From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year | Assessment of number of participants having ILI symptoms in the experimental or control group |
Countries
Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| M-001 Participants will be vaccinated with 1mg dose of M-001 twice: Once at Day 0, and once at Day 21.
M-001: A recombinant protein containing 9 conserved epitopes from Influenza A and B that are common to the vast majority of influenza viruses. | 6,229 |
| Saline Participants will be vaccinated with saline twice: Once at Day 0, and once at Day 21.
Saline: 0.9% sodium chloride (NaCl) | 6,229 |
| Total | 12,458 |
Baseline characteristics
| Characteristic | M-001 | Saline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3147 Participants | 3148 Participants | 6295 Participants |
| Age, Categorical Between 18 and 65 years | 3082 Participants | 3081 Participants | 6163 Participants |
| Age, Continuous | 64.6 years STANDARD_DEVIATION 8.7 | 64.6 years STANDARD_DEVIATION 8.7 | 64.6 years STANDARD_DEVIATION 8.7 |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 6227 Participants | 6228 Participants | 12455 Participants |
| Region of Enrollment Bulgaria | 1751 participants | 1749 participants | 3500 participants |
| Region of Enrollment Croatia | 78 participants | 82 participants | 160 participants |
| Region of Enrollment Georgia | 258 participants | 256 participants | 514 participants |
| Region of Enrollment Hungary | 187 participants | 184 participants | 371 participants |
| Region of Enrollment Latvia | 268 participants | 273 participants | 541 participants |
| Region of Enrollment Poland | 2740 participants | 2736 participants | 5476 participants |
| Region of Enrollment Ukraine | 947 participants | 949 participants | 1896 participants |
| Sex: Female, Male Female | 3454 Participants | 3486 Participants | 6940 Participants |
| Sex: Female, Male Male | 2775 Participants | 2743 Participants | 5518 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 26 / 6,230 | 29 / 6,230 |
| other Total, other adverse events | 781 / 6,230 | 760 / 6,230 |
| serious Total, serious adverse events | 185 / 6,230 | 177 / 6,230 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Events, New Onset Chronic Illness, and Non-solicited Adverse Events
Number of participants with one or more Serious Adverse Events, New Onset Chronic illness, and Non-solicited Adverse Events assessed during one flu season per participant
Time frame: From Day 0 to end of study completion by participant which coincides with end of flu season in the respective year, an average of 4 months per participant per year
Population: Safety population comprises all subjects enrolled
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M-001 | Number of Participants With One or More Serious Adverse Events, New Onset Chronic Illness, and Non-solicited Adverse Events | Serious Adverse Events | 185 participants |
| M-001 | Number of Participants With One or More Serious Adverse Events, New Onset Chronic Illness, and Non-solicited Adverse Events | New Onset Chronic Illness | 167 participants |
| M-001 | Number of Participants With One or More Serious Adverse Events, New Onset Chronic Illness, and Non-solicited Adverse Events | Non-solicited Adverse Events | 781 participants |
| Saline | Number of Participants With One or More Serious Adverse Events, New Onset Chronic Illness, and Non-solicited Adverse Events | Serious Adverse Events | 177 participants |
| Saline | Number of Participants With One or More Serious Adverse Events, New Onset Chronic Illness, and Non-solicited Adverse Events | New Onset Chronic Illness | 166 participants |
| Saline | Number of Participants With One or More Serious Adverse Events, New Onset Chronic Illness, and Non-solicited Adverse Events | Non-solicited Adverse Events | 760 participants |
Primary
Number of Participants With qRT-PCR or Culture-confirmed Influenza-like Illness
Prevention of influenza disease by comparing the occurrence of either qRT-PCR or culture confirmed influenza in the M-001 experimental group vs. placebo caused by any influenza A or B virus in association with a protocol defined Influenza Like Illness.
Time frame: From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year
Population: Per protocol population comprises all subjects who received both doses of vaccine or placebo and had at least one contact with study staff after 15 days or more upon second vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| M-001 | Number of Participants With qRT-PCR or Culture-confirmed Influenza-like Illness | Both seasons | 160 Participants |
| M-001 | Number of Participants With qRT-PCR or Culture-confirmed Influenza-like Illness | Season 2018/2019 | 74 Participants |
| M-001 | Number of Participants With qRT-PCR or Culture-confirmed Influenza-like Illness | Season 2019/2020 | 86 Participants |
| Saline | Number of Participants With qRT-PCR or Culture-confirmed Influenza-like Illness | Both seasons | 138 Participants |
| Saline | Number of Participants With qRT-PCR or Culture-confirmed Influenza-like Illness | Season 2018/2019 | 60 Participants |
| Saline | Number of Participants With qRT-PCR or Culture-confirmed Influenza-like Illness | Season 2019/2020 | 78 Participants |
Secondary
Number of Participants With Culture-confirmed Influenza Incidence
Occurrence of culture confirmed influenza in the M-001 experimental group vs. placebo caused by any influenza A or B virus in association with a protocol defined Influenza Like Illness.
Time frame: From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year
Population: Per protocol population comprises all subjects who received both doses of vaccine or placebo and had at least one contact with study staff after 15 days or more upon second vaccination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M-001 | Number of Participants With Culture-confirmed Influenza Incidence | 111 Participants |
| Saline | Number of Participants With Culture-confirmed Influenza Incidence | 96 Participants |
Secondary
Number of Participants With Influenza-like Illness Symptoms
Assessment of number of participants having ILI symptoms in the experimental or control group
Time frame: From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year
Population: Per protocol population comprises all subjects who received both doses of vaccine or placebo and had at least one contact with study staff after 15 days or more upon second vaccination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M-001 | Number of Participants With Influenza-like Illness Symptoms | 1231 Participants |
| Saline | Number of Participants With Influenza-like Illness Symptoms | 1266 Participants |
Secondary
Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza
Assessed by reduction of severity of either qRT-PCR or culture-confirmed influenza illness by the reduction due to M-001 in the average number of days with respiratory or systemic symptoms during the first laboratory-confirmed influenza illness episode.
Time frame: From Day 14 post-second vaccination day to end of influenza season, an average of 4 months per participant per year
Population: Per protocol population comprises all subjects who received both doses of vaccine or placebo and had at least one contact with study staff after 15 days or more upon second vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| M-001 | Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza | < 7 days | 13 Participants |
| M-001 | Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza | >= 7 - 14 days | 94 Participants |
| M-001 | Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza | >=14 - 21 days | 29 Participants |
| M-001 | Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza | >= 21 days | 24 Participants |
| Saline | Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza | >= 21 days | 26 Participants |
| Saline | Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza | < 7 days | 12 Participants |
| Saline | Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza | >=14 - 21 days | 29 Participants |
| Saline | Number of Participants With Reduction of Severity of qRT-PCR or Culture-confirmed Influenza | >= 7 - 14 days | 71 Participants |