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 3 dose levels in adjuvanted (SE) rHA formulations and 1 dose levels in an un-adjuvanted rHA formulation.
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
BIOLOGICALPanBlok
Intramuscular injection
BIOLOGICALrHA adjuvant
Intramuscular injection
Sponsors
Protein Sciences Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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
* Young adults aged 18-49 years * Able to give written informed consent to participate. * Vital signs within normal limits. * The subject must be in good health as determined by targeted physical examination, when necessary, based on medical history. Stable medical condition is defined as: no recent change in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months. Any change that is due to change of health care provider, insurance company, etc., or is done for financial reasons, as long as in the same class of medication, will not be considered a violation of the inclusion criterion. Any change to prescription medication due to improvement of a disease outcome will not be considered a violation of the inclusion criterion. * Comprehensive Metabolic Panel and other tests for the following must fall within normal limits or not exceed a Grade 1 abnormality at screening. Any Grade 1 abnormality must be clinically acceptable to the investigator in the context of other parameters such the subject's medical history. However, this will not apply to an above the upper limit of the normal range for ALT. Subjects with values above the upper limit of the normal range for ALT at the screening visit will not be enrolled. * Complete Blood Count with Cell Differential and urinalysis must fall within normal limits at screening except when clinically acceptable to the investigator in the context of other parameters such the subject's medical history. * Women of child-bearing potential (WOCBP) must have a negative urine pregnancy test within 24 hours preceding receipt of first and second vaccine doses. * WOCBP must use medically acceptable contraception. * Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits.
Exclusion criteria
* Previously received an H5N1 influenza vaccine or who plan to receive an H5N1 influenza vaccine while participating in the study * An acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses * Medications or treatments that may adversely affect the immune system * An active neoplastic disease or a history of any hematological malignancy. For this criterion, active is defined as having received treatment within the past 5 years. * A long-term use of supraphysiologic doses of oral or parenteral steroids, or high-dose inhaled steroids within the preceding 6 months. * A history of documented autoimmune disease. * Pregnant, nursing mothers or women planning a pregnancy between enrollment and 42 days after randomization * Prior serious reaction to any influenza vaccine * History of Guillain-Barré Syndrome * History of anaphylactic-type reaction to injected vaccines * History of illicit drug use or alcohol abuse in the year preceding the study * Received a seasonal influenza vaccine six months prior to enrollment * Received any licensed inactivated or recombinant vaccine within 2 weeks prior to enrollment or any licensed live vaccine within 1 month prior to enrollment. * Acute illness or fever within three days prior to study enrollment * Participating in a study that involves an experimental agent or have received an experimental agent within 1 month prior to enrollment in this study, or who expect to receive another experimental agent during participation, or intend to donate blood during the 42-day primary study period. * Received or expect to receive immunoglobulin or another blood product within the 3 months prior to enrollment in this study. * An elevated liver function enzyme of ALT at baseline, regardless of the appraisal of clinical significance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Difference in Seroconversion/Immunogenicity Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone. | 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 a non-adjuvanted rHA treatment group for whether they demonstrated seroconversion rates and 95% confidence intervals. |
| The Difference in Geometric Mean Titer Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone. | 42 Days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reactogenicity Immediately After Each Injection, Extending to Day 7. | 7 Days | Solicited events of local and systemic reactogenicity Days 0-7. These events are expected to occur and not considered or recorded as Adverse Events. |
| Long-term Safety | 13 Months | Incidence of Serious Adverse Events (SAEs), New Onset of Chronic Illnesses (NOCIs) and Adverse Events of Special Interest (AESIs) over 12 months following vaccination. Study subjects were followed every three months (for one year following Day 42) by telephone and visit for reports of SAEs, NOCIs, and AESIs. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PanBlok 15µg in 2% SE 15µg recombinant hemagglutinin in a 2% oil-in-water stable emulsion (rHA adjuvant). 0.5mL intramuscular injection on Day 0 and Day 21 in the deltoid muscle
PanBlok: Intramuscular injection
rHA adjuvant: Intramuscular injection | 84 |
| PanBlok 3.8µg in 2% SE 3.8µg recombinant hemagglutinin in a 2% oil-in-water stable emulsion (rHA adjuvant). 0.5mL intramuscular injection on Day 0 and Day 21 in the deltoid muscle
PanBlok: Intramuscular injection
rHA adjuvant: Intramuscular injection | 86 |
| PanBlok 7.5µg No Adjuvant 7.5µg recombinant hemagglutinin, no adjuvant. 0.5mL intramuscular injection on Day 0 and Day 21 in the deltoid muscle
PanBlok: Intramuscular injection | 85 |
| PanBlok 7.5µg in 2% SE 7.5µg recombinant hemagglutinin in a 2% oil-in-water stable emulsion (rHA adjuvant). 0.5mL intramuscular injection on Day 0 and Day 21 in the deltoid muscle
PanBlok: Intramuscular injection
rHA adjuvant: Intramuscular injection | 86 |
| Total | 341 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 6 | 4 | 4 | 8 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | Total | PanBlok 7.5µg in 2% SE | PanBlok 7.5µg No Adjuvant | PanBlok 15µg in 2% SE | PanBlok 3.8µg in 2% SE |
|---|---|---|---|---|---|
| Age, Continuous | 31 years | 30 years | 32 years | 32 years | 31 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants | 12 Participants | 12 Participants | 8 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 299 Participants | 74 Participants | 73 Participants | 76 Participants | 76 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 96 Participants | 25 Participants | 21 Participants | 28 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 7 Participants | 0 Participants | 3 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 224 Participants | 58 Participants | 56 Participants | 52 Participants | 58 Participants |
| Region of Enrollment United States | 341 participants | 86 participants | 85 participants | 84 participants | 86 participants |
| Sex: Female, Male Female | 207 Participants | 48 Participants | 49 Participants | 52 Participants | 58 Participants |
| Sex: Female, Male Male | 134 Participants | 38 Participants | 36 Participants | 32 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 84 | 13 / 86 | 24 / 85 | 16 / 86 |
| serious Total, serious adverse events | 0 / 84 | 2 / 86 | 1 / 85 | 2 / 86 |
Outcome results
Primary
The Difference in Geometric Mean Titer Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone.
Time frame: 42 Days
Population: All subjects who received both doses of study vaccine and had pre- and post-immunization immunogenicity data for the time period summarized.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| PanBlok 15µg in 2% SE | The Difference in Geometric Mean Titer Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone. | 121.7 titer |
| PanBlok 3.8µg in 2% SE | The Difference in Geometric Mean Titer Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone. | 76.1 titer |
| PanBlok 7.5µg No Adjuvant | The Difference in Geometric Mean Titer Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone. | 7.1 titer |
| PanBlok 7.5µg in 2% SE | The Difference in Geometric Mean Titer Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone. | 77.5 titer |
Primary
The Difference in Seroconversion/Immunogenicity Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone.
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 a non-adjuvanted rHA treatment group for whether they demonstrated seroconversion rates and 95% confidence intervals.
Time frame: 42 Days
Population: All subjects who received both doses of study vaccine and had pre- and post-immunization immunogenicity data for the time period summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PanBlok 15µg in 2% SE | The Difference in Seroconversion/Immunogenicity Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone. | 83 percentage of participants |
| PanBlok 3.8µg in 2% SE | The Difference in Seroconversion/Immunogenicity Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone. | 70 percentage of participants |
| PanBlok 7.5µg No Adjuvant | The Difference in Seroconversion/Immunogenicity Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone. | 9 percentage of participants |
| PanBlok 7.5µg in 2% SE | The Difference in Seroconversion/Immunogenicity Between rHA Formulated in an oil-in- Water Adjuvant (SE) Compared to a rHA Antigen Alone. | 76 percentage of participants |
Secondary
Long-term Safety
Incidence of Serious Adverse Events (SAEs), New Onset of Chronic Illnesses (NOCIs) and Adverse Events of Special Interest (AESIs) over 12 months following vaccination. Study subjects were followed every three months (for one year following Day 42) by telephone and visit for reports of SAEs, NOCIs, and AESIs.
Time frame: 13 Months
Population: All randomized subjects who received at least one dose of study vaccine and provided any safety data following vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PanBlok 15µg in 2% SE | Long-term Safety | SAEs | 0 participants |
| PanBlok 15µg in 2% SE | Long-term Safety | AESIs | 0 participants |
| PanBlok 15µg in 2% SE | Long-term Safety | NOCIs | 0 participants |
| PanBlok 3.8µg in 2% SE | Long-term Safety | SAEs | 2 participants |
| PanBlok 3.8µg in 2% SE | Long-term Safety | AESIs | 0 participants |
| PanBlok 3.8µg in 2% SE | Long-term Safety | NOCIs | 0 participants |
| PanBlok 7.5µg No Adjuvant | Long-term Safety | SAEs | 1 participants |
| PanBlok 7.5µg No Adjuvant | Long-term Safety | NOCIs | 0 participants |
| PanBlok 7.5µg No Adjuvant | Long-term Safety | AESIs | 0 participants |
| PanBlok 7.5µg in 2% SE | Long-term Safety | SAEs | 2 participants |
| PanBlok 7.5µg in 2% SE | Long-term Safety | AESIs | 0 participants |
| PanBlok 7.5µg in 2% SE | Long-term Safety | NOCIs | 0 participants |
Secondary
Reactogenicity Immediately After Each Injection, Extending to Day 7.
Solicited events of local and systemic reactogenicity Days 0-7. These events are expected to occur and not considered or recorded as Adverse Events.
Time frame: 7 Days
Population: All randomized subjects who received at least one dose of study vaccine and provided any safety data following vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PanBlok 15µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Nausea/Vomiting | 1 participants |
| PanBlok 15µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Arthralgia | 4 participants |
| PanBlok 15µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site erythema | 0 participants |
| PanBlok 15µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site tenderness | 47 participants |
| PanBlok 15µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Myalgia | 11 participants |
| PanBlok 15µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Chills | 3 participants |
| PanBlok 15µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Fatigue | 6 participants |
| PanBlok 15µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Elevated temperature | 0 participants |
| PanBlok 15µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Headache | 8 participants |
| PanBlok 15µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site pain | 34 participants |
| PanBlok 15µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Diarrhea | 4 participants |
| PanBlok 3.8µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Fatigue | 9 participants |
| PanBlok 3.8µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Nausea/Vomiting | 6 participants |
| PanBlok 3.8µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Elevated temperature | 0 participants |
| PanBlok 3.8µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Diarrhea | 4 participants |
| PanBlok 3.8µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Chills | 0 participants |
| PanBlok 3.8µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site erythema | 1 participants |
| PanBlok 3.8µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site tenderness | 52 participants |
| PanBlok 3.8µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Arthralgia | 2 participants |
| PanBlok 3.8µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Myalgia | 17 participants |
| PanBlok 3.8µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Headache | 19 participants |
| PanBlok 3.8µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site pain | 34 participants |
| PanBlok 7.5µg No Adjuvant | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site pain | 6 participants |
| PanBlok 7.5µg No Adjuvant | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Elevated temperature | 0 participants |
| PanBlok 7.5µg No Adjuvant | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Fatigue | 9 participants |
| PanBlok 7.5µg No Adjuvant | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Chills | 2 participants |
| PanBlok 7.5µg No Adjuvant | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Myalgia | 7 participants |
| PanBlok 7.5µg No Adjuvant | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Headache | 13 participants |
| PanBlok 7.5µg No Adjuvant | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Nausea/Vomiting | 8 participants |
| PanBlok 7.5µg No Adjuvant | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Diarrhea | 7 participants |
| PanBlok 7.5µg No Adjuvant | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site tenderness | 8 participants |
| PanBlok 7.5µg No Adjuvant | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site erythema | 1 participants |
| PanBlok 7.5µg No Adjuvant | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Arthralgia | 4 participants |
| PanBlok 7.5µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Myalgia | 13 participants |
| PanBlok 7.5µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site pain | 32 participants |
| PanBlok 7.5µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Arthralgia | 4 participants |
| PanBlok 7.5µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Chills | 3 participants |
| PanBlok 7.5µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site erythema | 2 participants |
| PanBlok 7.5µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Injection site tenderness | 46 participants |
| PanBlok 7.5µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Fatigue | 9 participants |
| PanBlok 7.5µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Elevated temperature | 0 participants |
| PanBlok 7.5µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Diarrhea | 3 participants |
| PanBlok 7.5µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Nausea/Vomiting | 3 participants |
| PanBlok 7.5µg in 2% SE | Reactogenicity Immediately After Each Injection, Extending to Day 7. | Headache | 8 participants |