Safety and Immunogenicity of PanBlok Influenza Vaccine in Healthy Adults

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 2 Observer-Blind, Randomized Trial to Evaluate the Immunogenicity and Safety of PanBlok at Three Dose Levels Adjuvanted With a Stable Oil-in-Water Emulsion Compared With PanBlok Without Adjuvant in Healthy Adults Aged 18 to 49 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: PanBlok
* Biological: rHA adjuvant


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PanBlok 15µg in 2% SE<br>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 | Biological: PanBlok<br>* Intramuscular injection<br>* Other names: recombinant hemagglutinin;Biological: rHA adjuvant<br>* Intramuscular injection<br>* Other names: SE;|
| Experimental: PanBlok 3.8µg in 2% SE<br>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 | Biological: PanBlok<br>* Intramuscular injection<br>* Other names: recombinant hemagglutinin;Biological: rHA adjuvant<br>* Intramuscular injection<br>* Other names: SE;|
| Experimental: PanBlok 7.5µg No Adjuvant<br>7.5µg recombinant hemagglutinin, no adjuvant. 0.5mL intramuscular injection on Day 0 and Day 21 in the deltoid muscle | Biological: PanBlok<br>* Intramuscular injection<br>* Other names: recombinant hemagglutinin;|
| Experimental: PanBlok 7.5µg in 2% SE<br>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 | Biological: PanBlok<br>* Intramuscular injection<br>* Other names: recombinant hemagglutinin;Biological: rHA adjuvant<br>* Intramuscular injection<br>* Other names: SE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 42 Days | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 7 Days | 
| 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. | 13 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza