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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Influenza
- Sponsor
- Protein Sciences Corporation
- Enrollment
- 407
- Locations
- 8
- Primary Endpoint
- Demonstrate That the Immunogenicity of Adjuvanted Panblok H7 rHA is Sufficient to Support Emergency Use Authorization in the Event of a Declared Pandemic.
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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.
Outcomes
Primary Outcomes
Demonstrate That the Immunogenicity of Adjuvanted Panblok H7 rHA is Sufficient to Support Emergency Use Authorization in the Event of a Declared Pandemic.
Time Frame: 42 Days
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.
Secondary Outcomes
- Unsolicited Adverse Events (UAEs) During Days 0-42 Following the First Administration of Study Vaccine(42 Days)
- Reactogenicity Immediately After Each Injection, Extending to Day 7(7 Days)
- Long-term Safety Assessed by Incidence of SAEs, NOCIs. AESs Over 12 Months Following Vaccination(13 months)