A Phase II Randomized, Double-Blinded, Controlled Study in Healthy Adults to Assess the Safety, Reactogenicity, and Immunogenicity of a Monovalent Influenza A/H7N9 Virus Vaccine Administered at Different Dosages Given With and Without AS03 and MF59 Adjuvants
Overview
- Phase
- Phase 2
- Intervention
- AS03
- Conditions
- Influenza
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 980
- Locations
- 5
- Primary Endpoint
- Occurrence of clinical safety laboratory adverse events from the time of each study vaccination through approximately 8 days after each study vaccination.
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This Phase II randomized, double-blinded, controlled study in up to 1000 males and non-pregnant females, 19 to 64 years old, inclusive, who are in good health and meet all eligibility criteria is designed to provide data on an A/H7N9 vaccine made with HA antigen derived from the influenza A/Shanghai/2/2013 virus.
Detailed Description
This Phase II randomized, double-blinded, controlled study in up to 1000 males and non-pregnant females, 19 to 64 years old, inclusive, who are in good health and meet all eligibility criteria is designed to provide data on an A/H7N9 vaccine made with HA antigen derived from the influenza A/Shanghai/2/2013 virus. The study aims to address several critical questions, including the safety, reactogenicity, and immunogenicity of a monovalent influenza A/H7N9 virus vaccine manufactured by Sanofi Pasteur: 1) two doses administered at different dosages (3.75, 7.5, or 15 mcg of HA/0.5 mL dose) given with AS03 adjuvant manufactured by GlaxoSmithKline Biologicals or without adjuvant (15 mcg of HA/0.5 mL dose and 45 mcg of HA/0.75 mL dose); and 2) a combination of two doses of the A/H7N9 vaccine (15 mcg of HA/0.5 mL dose) each administered with a different adjuvant (AS03 or MF59 manufactured by Novartis Vaccines and Diagnostics); and 3) two doses administered at 15 mcg of HA/0.5 mL dose given with MF59 adjuvant manufactured by Novartis Vaccines and Diagnostics.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provide written informed consent prior to initiation of any study procedures.
- •Are able to understand and comply with planned study procedures and be available for all study visits.
- •Are males or non-pregnant females, 19 to 64 years old, inclusive.
- •Are in good health, as determined by vital signs (oral temperature, pulse, and blood pressure), medical history, and targeted physical examination based on medical history to ensure any existing medical diagnoses or conditions (except those in the Subject Exclusion Criteria) are stable . Subjects may be on chronic1 or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity. Note: Topical, nasal, and inhaled medications (with the exception of steroids as outlined in the Subjects Exclusion Criteria (see Section 5.2), vitamins, and contraceptives are permitted.
- •Oral temperature is less than 100.4 degrees F.
- •Pulse is 50 to 115 bpm, inclusive.
- •Systolic blood pressure is 85 to 150 mm Hg, inclusive.
- •Diastolic blood pressure is 55 to 95 mmHg, inclusive.
- •Erythrocyte sedimentation rate (ESR) is less than 30 mm per hour.
- •Alanine aminotransferase (ALT) is less than 44 IU/L for females or is less than 61 IU/L for males.
Exclusion Criteria
- •Have an acute illness within 72 hours prior to study vaccination.
- •Have any condition that, in the opinion of the site principal investigator or appropriate sub-investigator, would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or confound the interpretation of the results.
- •Have an acute or chronic medical condition that, in the opinion of the site principal investigator or appropriate sub-investigator, would render vaccination unsafe, or would interfere with the evaluation of responses.
- •Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
- •Have known active neoplastic disease or a history of any hematologic malignancy.
- •Have known HIV, hepatitis B, or hepatitis C infection.
- •Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccine.
- •Have a history of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines.
- •Have a personal or family history of narcolepsy with or without cataplexy.
- •Have a history of Guillain-Barré Syndrome.
Arms & Interventions
Group 4
100 subjects receive 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 0 and 15mcg sanofi A/H7N9 antigen on Day 21
Intervention: AS03
Group 4
100 subjects receive 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 0 and 15mcg sanofi A/H7N9 antigen on Day 21
Intervention: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
Group 7
100 subjects receive 15mcg sanofi A/H7N9 antigen plus NVD MF59 adjuvant on Day 0 and 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 21
Intervention: AS03
Group 3
100 subjects receive 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 0 and 21
Intervention: AS03
Group 3
100 subjects receive 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 0 and 21
Intervention: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
Group 1
100 subjects receive 3.75mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 0 and 21
Intervention: AS03
Group 1
100 subjects receive 3.75mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 0 and 21
Intervention: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
Group 2
100 subjects receive 7.5mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 0 and 21
Intervention: AS03
Group 2
100 subjects receive 7.5mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 0 and 21
Intervention: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
Group 5
100 subjects receive 15mcg sanofi A/H7N9 antigen on Day 0 and 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 21
Intervention: AS03
Group 5
100 subjects receive 15mcg sanofi A/H7N9 antigen on Day 0 and 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 21
Intervention: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
Group 9
100 subjects receive 15mcg sanofi A/H7N9 antigen on Day 0 and 21
Intervention: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
Group 8
100 subjects receive 15mcg sanofi A/H7N9 antigen plus NVD MF59 adjuvant on Day 0 and 21
Intervention: MF59
Group 8
100 subjects receive 15mcg sanofi A/H7N9 antigen plus NVD MF59 adjuvant on Day 0 and 21
Intervention: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
Group 7
100 subjects receive 15mcg sanofi A/H7N9 antigen plus NVD MF59 adjuvant on Day 0 and 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 21
Intervention: MF59
Group 7
100 subjects receive 15mcg sanofi A/H7N9 antigen plus NVD MF59 adjuvant on Day 0 and 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 21
Intervention: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
Group 6
100 subjects receive 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 0 and 15mcg sanofi A/H7N9 antigen plus NVD MF59 adjuvant on Day 21
Intervention: AS03
Group 6
100 subjects receive 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 0 and 15mcg sanofi A/H7N9 antigen plus NVD MF59 adjuvant on Day 21
Intervention: MF59
Group 6
100 subjects receive 15mcg sanofi A/H7N9 antigen plus GSK AS03 adjuvant on Day 0 and 15mcg sanofi A/H7N9 antigen plus NVD MF59 adjuvant on Day 21
Intervention: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
Group 10
100 subjects receive 45 mcg sanofi A/H7N9 antigen on Day 0 and 21
Intervention: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
Outcomes
Primary Outcomes
Occurrence of clinical safety laboratory adverse events from the time of each study vaccination through approximately 8 days after each study vaccination.
Time Frame: Day 0 through Day 29
Percentage of subjects achieving seroconversion (defined as either a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer >/=1:40 or a pre-vaccination HAI titer >/=1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer).
Time Frame: Day 42 (21 days post second study vaccination)
Occurrence of solicited injection site and systemic reactogenicity on the day of each study vaccination through 7 days after each study vaccination.
Time Frame: Day 0 though Day 29
Occurrence of study vaccine-related serious adverse events from the time of the first study vaccination through approximately 13 months after the first study vaccination.
Time Frame: Day 0 through Day 386
Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine at approximately 21 days after the second study vaccination.
Time Frame: Day 42 (21 days post second study vaccination)
Secondary Outcomes
- Percentage of subjects achieving a serum Neut antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine at baseline and at approximately 8 and 21 days after each study vaccination(Day 0, 8, 21, 29, and 42)
- Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine at approximately 8 days after the second study vaccination.(Day 29 (8 days after the second study vaccination))
- Occurrence of new-onset chronic medical conditions through 13 months after the first study vaccination.(Through Day 386 (13 months after the first vaccination))
- Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine at baseline and at approximately 8 and 21 days after the first study vaccination.(Days 0, 8 and 21)
- Percentage of subjects achieving seroconversion (defined as either a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer >/=1:40 or a pre-vaccination HAI titer >/=1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer)(Day 0, 8 and 21)
- Percentage of subjects achieving seroconversion (defined as either a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer >/=1:40 or a pre-vaccination HAI titer >/=1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer).(Day 29 (8 days after the second study vaccination))
- Occurrence of unsolicited adverse events from the time of the first study vaccination through approximately 21 days after the last study vaccination.(Day 42 (21 days post last study vaccination)
- Percentage of subjects achieving seroconversion (defined as either a pre-vaccination Neut titer <1:10 and a post-vaccination Neut titer >/= 1:40 or a pre-vaccination Neut titer >/=1:10 and a minimum four-fold rise in post-vaccination Neut antibody titer)(Day 0, 8, 21, 29, and 42)
- Geometric Mean Titers of serum HAI and Neut antibody at baseline and at approximately 8 and 21 days after each study vaccination.(Days 0, 8, 21, 29, and 42)