Trial to Evaluate the Immunogenicity and Safety of Panblok® (H7 rHA) in Healthy Adults Aged 18 and Older

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/Anhui/1/2013 (H7N9) administered at 3 dose levels in adjuvanted (SE) rHA formulations and 1 dose levels in an unadjuvanted 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 1/2 Adaptive Design Trial to Evaluate the Immunogenicity and Safety of Panblok (H7 rHA) at Three Dose Levels Adjuvanted With a Stable Oil-in-Water Emulsion Compared With Unadjuvanted H7 rHA in Healthy Adults Aged 18 and Older

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: Adults, regardless of gender, aged 18 years and above Able to give written informed consent to participate. Body temperature <100.0ºF. The subject must be in reasonably good health as determined by targeted physical examination, when necessary, based on 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. Women are considered not of child-bearing potential if they are: Surgically sterile Menopausal, defined as no natural menses for ≥12 months Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits and remote contacts. Exclusion Criteria: Persons who previously received an H5N1 or H7N9 influenza vaccine or who plan to receive an H5N1or H7N9 influenza vaccine while participating in the study. Persons who plan to receive a seasonal influenza vaccine earlier than Day 42 of participation in this study, i.e. before the post-vaccination serology sample is obtained. Persons with an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of immune responses. Persons taking medications or treatments that may adversely affect the immune system, e.g. cytotoxic agents, immunosuppressive doses of corticosteroids, anti-TNFα agents. Persons with an active neoplastic disease (excluding non-melanoma skin cancer that was successfully treated) or a history of any hematological malignancy. For this criterion, active is defined as having received treatment within the past 5 years. Persons with a history of documented autoimmune disease. Women currently pregnant, nursing mothers or women planning a pregnancy between enrollment and 42 days after randomization. Persons who have had a prior serious reaction to any influenza vaccine. Persons with a known history of Guillain-Barré Syndrome (GBS). Persons with a history of anaphylactic-type reaction to injected vaccines. Persons with a history of illicit drug use or alcohol abuse that may compromise the subject's ability to comply with the protocol. Persons who received a seasonal influenza vaccine < 6 months prior to enrollment (may delay enrollment). Persons who received any licensed inactivated or recombinant (non-live) vaccine within 2 weeks prior to enrollment or any licensed live vaccine within 1 month prior to enrollment (may delay enrollment) (See separate exclusion criteria #1 and #12 for seasonal and H5N1 influenza vaccines.) Persons who have had an acute illness or fever (>38º C or >100º F) within three days prior to study enrollment (enrollment may be delayed for full recovery, if acceptable to investigator). Persons currently participating or planning to participate in a study that involves an experimental agent (vaccine, drug, biologic, device, or medication) 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. Persons who received immunoglobulin or another blood product within the 3 months prior to enrollment in this study. Persons who expect to receive immunoglobulin or another blood product during the 42-day primary period of this study.

Ages Eligible for Study
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Minimum Age: 18 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 30µg in 2% SE<br>30µg 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: rHA;Biological: rHA adjuvant<br>* Intramuscular injection<br>* Other names: SE;|
| 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: rHA;Biological: rHA adjuvant<br>* Intramuscular injection<br>* Other names: SE;|
| 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: rHA;Biological: rHA adjuvant<br>* Intramuscular injection<br>* Other names: SE;|
| Experimental: Panblok 30µg (No Adjuvant)<br>30µg 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: rHA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrate That the Immunogenicity of Adjuvanted Panblok H7 rHA is Sufficient to Support Emergency Use Authorization in the Event of a Declared Pandemic. | The primary endpoint will be seroprotection rate to the selected dose of adjuvanted H7 rHA, defined by a post-vaccination HAI titer ≥40 on Day 42. The definition of success will be a lower bound of the two-sided 95% CI ≥ 70% for adults <65 and ≥60% for adults ≥65 years of age. | 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 | 7 Days | 
| Long-term Safety Assessed by Incidence of SAEs, NOCIs. AESs Over 12 Months Following Vaccination |  | 13 months | 
| Unsolicited Adverse Events (UAEs) During Days 0-42 Following the First Administration of Study Vaccine | Unsolicited adverse events (UAEs) Days 0-42. | 42 Days | 

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