Influenza
Conditions
Keywords
Influenza
Brief summary
The purpose of this study is to investigate the safety and immunogenicity of a recombinant hemagglutinin (rHA) influenza vaccine derived from A/Indonesia/05/2005 (H5N1) administered at 4 dose levels in adjuvanted (GLA-SE) rHA formulations and 2 dose levels in unadjuvanted rHA formulations.
Detailed description
All currently licensed influenza vaccines in the United States are produced in embryonated hen's eggs. There are several well-recognized disadvantages to the use of eggs as the substrate for influenza vaccine. Eggs require specialized manufacturing facilities and could be difficult to scale up rapidly in response to an emerging need such as a pandemic. It is usually necessary to adapt candidate vaccine viruses for high-yield growth in eggs, a process that can be time consuming, is not always successful, and can select receptor variants that may have suboptimal immunogenicity. In addition, agricultural diseases that affect chicken flocks, and that might be an important issue in a pandemic due to an avian influenza virus strain, could easily disrupt the supply of eggs for vaccine manufacturing. Therefore, development of alternative substrates for influenza vaccine production has been identified as a high-priority objective. One potential alternative method for production of influenza vaccine is expression of the influenza virus hemagglutinin (HA) using recombinant DNA techniques. This alternative avoids dependence on eggs and is very efficient because of the high levels of protein expression under the control of the baculovirus polyhedrin promoter.
Interventions
BIOLOGICAL0.5mL Intramuscular Injection
0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle
Sponsors
Protein Sciences Corporation
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female aged 18-49 years. * Give written informed consent to participate. * Healthy, as determined by medical history, physical examination, vital signs, and clinical safety laboratory evaluation * Females should fulfill one of the following criteria: * At least one year post-menopausal; * Surgically sterile; * Will use oral, implantable, transdermal or injectable contraceptives for 30 days prior to first vaccination and until 28 days after the booster vaccination; or * Willing to use another reliable form of contraception approved by the Investigator (e.g., intrauterine device (IUD), female condom, diaphragm with spermicide, cervical cap, use of condom by the sexual partner or a sterile sexual partner) for 30 days prior to first vaccination and until 28 days after the booster vaccination. * Women of childbearing potential must have a negative urine pregnancy test within 24 hours preceding receipt of first and booster vaccinations * Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits.
Exclusion criteria
* Persons under 18 years old or 50 years or older * Persons with chronic illnesses such as cancer, diabetes, liver or kidney disease * Persons taking medications or treatments that may adversely affect the immune system * Persons with known allergy to eggs or other vaccine or adjuvant components * Person currently pregnant, nursing mothers or planning a pregnancy within one month of vaccination * Persons who have had a prior serious reaction to any influenza vaccine * Persons with a known history of Guillain-Barré Syndrome * Persons with a history of anaphylactic-type reaction to injected vaccines * Persons with a history of drug or chemical abuse in the year preceding the study * Persons who previously received an H5N1 influenza vaccine or who plan to receive an H5N1 influenza vaccine while participating in the study * Persons who received a seasonal influenza vaccine six months prior to enrollment (may delay enrollment) * Persons who received any other vaccine within one week prior to enrollment (may delay enrollment) * Persons who have had a respiratory illness or illness with fever within three days of study enrollment (may delay enrollment) * Persons currently participating in another research study involving any study medications (investigational drugs or vaccines).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age. | 42 Days | Immunogenicity was assessed by measuring the percentage of subjects in each group exhibiting seroconversion on Day 42. The treatment groups that received adjuvanted rHA were evaluated against non-adjuvanted rHA and placebo groups for whether they demonstrated seroconversion rates and 95% confidence intervals that met regulatory criterion for licensure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 0, and Day 42 | Immunogenicity was assessed by measuring the proportion of subjects that exhibited a geometric mean titer change from Day 0 to Day 42. The geometric mean titers from the PanBlok groups (with and without adjuvant)and placebo group were then compared. |
| Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age | 21 Days | Immunogenicity was assessed by measuring the seroconversion rates of subjects from Day 0 to Day 21 to determine and evaluate the immune response following a single dose of study vaccine. The results were compared using PanBlok with and without adjuvant and placebo in healthy adults |
Countries
United States
Participant flow
Recruitment details
Healthy adults 18-49 years of age were screened in participating outpatient clinics for eligibility within 30 days of randomization during the 2010 influenza season.
Pre-assignment details
Subjects whose laboratory values were exclusionary were not randomized. Women of child-bearing potential were required to have a negative pregnancy test.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 0.9% Sodium Chloride; Two 0.5 mL IM injections 21 days apart
0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle | 60 |
| PanBlok 135µg No Adjuvant 135µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart
0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle | 57 |
| PanBlok 45µg No Adjuvant 45µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart
0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle | 55 |
| PanBlok 45µg and GLA 1.0µg, SE 2% 45µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart
0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle | 56 |
| PanBlok 15µg and GLA 1.0µg, SE 2% 15µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart
0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle | 56 |
| PanBlok 7.5µg and GLA 1.0µg, SE 2% 7.5µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart
0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle | 53 |
| PanBlok 3.8µg and GLA 1.0µg, SE 2% 3.8µg recombinant hemagglutinin and Glucopyranosyl Lipid A 1.0µg in a 2% oil-in-water stable emulsion; Two 0.5 mL IM injections 21 days apart
0.5mL Intramuscular Injection : 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle | 55 |
| Total | 392 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Subjects That Completed Safety Follow-up | Ineligible | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Subjects That Completed Safety Follow-up | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
| Subjects That Completed Safety Follow-up | Withdrawal by Subject | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Subjects That Received 2nd Dose | Did not complete the study | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Subjects That Received 2nd Dose | Ineligible | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Subjects That Received 2nd Dose | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| Subjects That Received 2nd Dose | Other | 0 | 3 | 3 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | PanBlok 135µg No Adjuvant | PanBlok 45µg No Adjuvant | PanBlok 45µg and GLA 1.0µg, SE 2% | PanBlok 15µg and GLA 1.0µg, SE 2% | PanBlok 7.5µg and GLA 1.0µg, SE 2% | PanBlok 3.8µg and GLA 1.0µg, SE 2% | Total |
|---|---|---|---|---|---|---|---|---|
| Age Continuous | 32.0 years | 30.0 years | 32.0 years | 31.0 years | 33.5 years | 27.0 years | 33.0 years | 32.2 years |
| Sex: Female, Male Female | 33 Participants | 35 Participants | 32 Participants | 30 Participants | 43 Participants | 34 Participants | 25 Participants | 232 Participants |
| Sex: Female, Male Male | 27 Participants | 22 Participants | 23 Participants | 26 Participants | 13 Participants | 19 Participants | 30 Participants | 160 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 39 / 60 | 36 / 57 | 33 / 55 | 35 / 56 | 40 / 56 | 32 / 53 | 38 / 55 |
| serious Total, serious adverse events | 1 / 60 | 2 / 57 | 1 / 55 | 1 / 56 | 2 / 56 | 0 / 53 | 3 / 55 |
Outcome results
Primary
Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age.
Immunogenicity was assessed by measuring the percentage of subjects in each group exhibiting seroconversion on Day 42. The treatment groups that received adjuvanted rHA were evaluated against non-adjuvanted rHA and placebo groups for whether they demonstrated seroconversion rates and 95% confidence intervals that met regulatory criterion for licensure.
Time frame: 42 Days
Population: All randomized subjects who received study vaccine and had Day 0 and Day 42 efficacy data. The analysis results are generated by Southern Research Institute on the intention to treat efficacy population using whole virus.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age. | 0 percentage of participants |
| PanBlok 135µg No Adjuvant | Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age. | 32 percentage of participants |
| PanBlok 45µg No Adjuvant | Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age. | 15 percentage of participants |
| PanBlok 45µg and GLA 1.0µg, SE 2% | Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age. | 82 percentage of participants |
| PanBlok 15µg and GLA 1.0µg, SE 2% | Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age. | 75 percentage of participants |
| PanBlok 7.5µg and GLA 1.0µg, SE 2% | Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age. | 66 percentage of participants |
| PanBlok 3.8µg and GLA 1.0µg, SE 2% | Evaluation of Immunogenicity Measured by Seroconversion Rates of PanBlok With and Without Adjuvant Compared to Placebo in Healthy Adults 18-49 Years of Age. | 72 percentage of participants |
Secondary
Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age.
Immunogenicity was assessed by measuring the proportion of subjects that exhibited a geometric mean titer change from Day 0 to Day 42. The geometric mean titers from the PanBlok groups (with and without adjuvant)and placebo group were then compared.
Time frame: Day 0, and Day 42
Population: All randomized subjects who received study vaccine and had Day 0 and Day 42 geometric mean titers. Analysis of results were generated by Southern Research Institute on the overall population using whole virus.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 0 | NA titer |
| Placebo | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 42 | NA titer |
| PanBlok 135µg No Adjuvant | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 0 | NA titer |
| PanBlok 135µg No Adjuvant | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 42 | 16.7 titer |
| PanBlok 45µg No Adjuvant | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 0 | NA titer |
| PanBlok 45µg No Adjuvant | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 42 | 10.7 titer |
| PanBlok 45µg and GLA 1.0µg, SE 2% | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 0 | NA titer |
| PanBlok 45µg and GLA 1.0µg, SE 2% | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 42 | 128.4 titer |
| PanBlok 15µg and GLA 1.0µg, SE 2% | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 0 | NA titer |
| PanBlok 15µg and GLA 1.0µg, SE 2% | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 42 | 94.5 titer |
| PanBlok 7.5µg and GLA 1.0µg, SE 2% | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 0 | NA titer |
| PanBlok 7.5µg and GLA 1.0µg, SE 2% | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 42 | 68.7 titer |
| PanBlok 3.8µg and GLA 1.0µg, SE 2% | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 0 | NA titer |
| PanBlok 3.8µg and GLA 1.0µg, SE 2% | Evaluation and Comparison of Immunogenicity From Geometric Mean Titers of PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age. | Day 42 | 71.7 titer |
Secondary
Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age
Immunogenicity was assessed by measuring the seroconversion rates of subjects from Day 0 to Day 21 to determine and evaluate the immune response following a single dose of study vaccine. The results were compared using PanBlok with and without adjuvant and placebo in healthy adults
Time frame: 21 Days
Population: All randomized subjects with Day 0 and Day 21 data analyzed by Cincinnati Children's Hospital Medical Center using the intent to treat population and CBER antigen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age | 3 percentage of participants |
| PanBlok 135µg No Adjuvant | Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age | 4 percentage of participants |
| PanBlok 45µg No Adjuvant | Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age | 4 percentage of participants |
| PanBlok 45µg and GLA 1.0µg, SE 2% | Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age | 11 percentage of participants |
| PanBlok 15µg and GLA 1.0µg, SE 2% | Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age | 7 percentage of participants |
| PanBlok 7.5µg and GLA 1.0µg, SE 2% | Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age | 8 percentage of participants |
| PanBlok 3.8µg and GLA 1.0µg, SE 2% | Serologic Response Rates at Day 21 Using PanBlok With and Without Adjuvant and Placebo in Healthy Adults 18-64 Years of Age | 2 percentage of participants |