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 4 dose levels in adjuvanted (GLA-SE) rHA formulations and 2 dose levels in unadjuvanted rHA formulations.

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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A Two-Part Placebo-Controlled Evaluation of the Safety and Immunogenicity of an A/Indonesia/5/05 Recombinant Hemagglutinin Influenza H5N1 Vaccine With and Without Glucopyranosyl Lipid A (GLA-SE) in Healthy Adults 18-49

Conditions
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Influenza

Intervention / Treatment
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* Biological: 0.5mL Intramuscular Injection


Participation Criteria
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Eligibility Criteria
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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).

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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PanBlok 135µg No Adjuvant<br>135µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart | Biological: 0.5mL Intramuscular Injection<br>* 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle<br>* Other names: PanBlok;|
| Experimental: PanBlok 45µg No Adjuvant<br>45µg recombinant hemagglutinin, no adjuvant; Two 0.5 mL IM injections 21 days apart | Biological: 0.5mL Intramuscular Injection<br>* 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle<br>* Other names: PanBlok;|
| Experimental: PanBlok 45µg and GLA 1.0µg, SE 2%<br>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 | Biological: 0.5mL Intramuscular Injection<br>* 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle<br>* Other names: PanBlok;|
| Experimental: PanBlok 15µg and GLA 1.0µg, SE 2%<br>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 | Biological: 0.5mL Intramuscular Injection<br>* 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle<br>* Other names: PanBlok;|
| Experimental: PanBlok 7.5µg and GLA 1.0µg, SE 2%<br>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 | Biological: 0.5mL Intramuscular Injection<br>* 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle<br>* Other names: PanBlok;|
| Experimental: PanBlok 3.8µg and GLA 1.0µg, SE 2%<br>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 | Biological: 0.5mL Intramuscular Injection<br>* 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle<br>* Other names: PanBlok;|
| Placebo Comparator: Placebo<br>0.9% Sodium Chloride; Two 0.5 mL IM injections 21 days apart | Biological: 0.5mL Intramuscular Injection<br>* 0.5mL intramuscular injection on day 0 and day 21 in the deltoid muscle<br>* Other names: PanBlok;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 0, and Day 42 | 
| 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 | 21 Days | 

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