Clinical trial NCT02126761: Safety and Immunogenicity of Different Formulations of an Adjuvanted, Trivalent Subunit Influenza Vaccine in Elderly Subjects 65 Years of Age and Above
Official title: A Phase 1, Randomized, Observer Blind, Antigen and Adjuvant Dosage-Finding Study to Evaluate the Safety and Immunogenicity of an Adjuvanted, Trivalent Subunit Influenza Vaccine in Elderly Subjects ≥65 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Keywords: Influenza
elderly
adjuvant
Lead sponsor: Seqirus
Sponsor class: INDUSTRY
Collaborators: name: Novartis Vaccines
First posted: 2014-04-30
Enrollment: 196
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: In this study, the safety and immunogenicity of the current formulation of aTIV will be compared to aTIV-modified formulations in which the dosage of the MF59 adjuvant will be doubled or tripled and/or the dosage of the 3 influenza virus strains will be doubled, in independently-living elderly subjects ≥ 65 years of age.


Eligibility criteria: Inclusion Criteria:

1. Male and female subjects ≥65 years of age on the day of screening who are healthy or have chronic illnesses that are stable and well controlled.
2. Subjects assessed as mentally competent, who have given informed consent after the nature of the study has been explained according to local requirements
3. In good health as determined by:

   1. Ability to live independently
   2. Medical history
   3. Physical examination
   4. Clinical judgment of the Investigator
4. Able to understand and comply with all study procedures and visits, and are able to complete an eDiary
5. Individuals who have access to a working telephone and are able to receive periodic telephone calls

Exclusion Criteria:

1. Individuals who have received any type of influenza vaccine (licensed or experimental) within the past 6 months
2. Individuals who have received any other licensed vaccines within 30 days (for inactivated vaccines) or 42 days (for live vaccines) prior to enrollment in this study
3. Individuals who have cancer except for:

   1. Benign localized skin cancer
   2. Localized prostate cancer that has been clinically stable for ≥ 2 years without treatment
   3. Cancer in remission for ≥ 10 years (from end of cancer treatment)
4. Individuals with autoimmune disease (including rheumatoid arthritis)
5. Individuals with diabetes mellitus, type I
6. Individuals with a body mass index (BMI) ≤18 or ≥35.
7. Asthma that is greater than mild in severity and / or has exacerbations more than 2 days per week
8. Congestive heart failure with symptoms as severe as or more severe than dyspnea with short walks or climbing a single flight of stairs (for example, greater than New York Heart Association class 2)
9. History of progressive or severe neurologic disorders including but not limited to multiple sclerosis, Parkinson's disease, Guillain-Barré syndrome, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, epilepsy disorders requiring medication for control, encephalitis, Alzheimer's and CVA
10. Individuals who are hypersensitive to ovalbumin, chicken protein, chicken feathers, influenza viral protein, kanamycin and neomycin sulfate or any other component of the vaccines in study
11. Individuals who have a history of neurological symptoms or signs, or anaphylactic shock following administration of any vaccine
12. Individuals who have a known or suspected (or have a high risk of developing) impairment/alteration of immune function resulting from, for example,

    a. Receipt of immunosuppressive therapy (defined as follows) within the past 60 days and/or anticipated to receive immunosuppressive therapy at any point within 21 days of Visit 1.

    i. Cancer chemotherapy/radiotherapy ii. Systemic corticosteroids ( i.e., 15 mg or greater per day of prednisone or equivalent) iii. Chronic use of inhaled/intranasal high potency corticosteroids (budesonide 800 μg per day or fluticasone 750 μg per day) b. Receipt of immunostimulants c. Receipt of parenteral immunoglobulin preparation, blood products and/or plasma derivate within the past 3 months and for the full length of the study d. Suspected or known HIV infection or HIV-related disease
13. Individuals who have a known or suspected history of drug or alcohol abuse
14. Individuals who, within the past 12 months, have had laboratory confirmed influenza disease
15. Individuals who, within the past 30 days have received any investigational agent.
16. Individuals who plan to receive another vaccine within 30 days of receipt of the study vaccination.
17. Individuals who, within the past 14 days, have experienced:

    1. Any acute disease including any worsening of underlying respiratory diseases such as asthma or COPD
    2. Infections requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable)
18. Individuals who are taking part in another clinical study
19. Individuals who are research staff directly involved with the clinical study or family members or household members of research staff. Research staff includes an individual with direct or indirect contact with study subjects, or study site personnel who have access to any study documents containing subject information. This would include receptionists, persons scheduling appointments or making screening calls, regulatory specialists, laboratory technicians, etc.
20. Individuals with behavioral or cognitive impairment or a psychiatric condition that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
21. Vulnerable subjects, e.g. subjects kept in detention, soldiers, employees of the sponsor or a clinical research organization involved in this study
22. Individuals who have any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.

Primary outcomes:
measure: Reactogenicity up to 7 days after vaccination
timeFrame: Days 1-7 post-vaccination
measure: Unsolicited AEs within 28 days after vaccination
timeFrame: Days 1-28 post-vaccination
measure: SAEs, non-scheduled physician visits, unsolicited medically attended AEs, unsolicited AEs leading to study withdrawal, NOCDs, and AESIs from study start to study completion.
timeFrame: Days 1-366 post-vaccination
measure: Seroconversion/significant increase in antibody HI titers; ≥4-fold rise in MN titer 21 days post-vaccination.
timeFrame: Day 22 post-vaccination
measure: HI and MN GMT and GMR at baseline and 21 days post-vaccination.
timeFrame: Day 1; Day 22 post-vaccination
Secondary outcomes:
measure: Seroconversion/significant increase in antibody HI titers; ≥4-fold rise in MN titer, 7 days and 6 months post-vaccination.
timeFrame: Day 8 and 181 post-vaccination
measure: HI and MN (GMT) 7 days and 6 months post-vaccination.
timeFrame: Day 8 and 181 post-vaccination
measure: HI and MN (GMR) 7 days, 21 days, and 6 months post-vaccination.
timeFrame: Day 1, 8, 22, and 181 post-vaccination
measure: Percentage of subjects with HI titers ≥1:40, ≥1:110, ≥1:160, and ≥1:330 7 days, 21 days, and 6 months post-vaccination.
timeFrame: Day 8, 22, and 181 post-vaccination
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: PAREXEL Early Phase Clinical Unit
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines
role: STUDY_CHAIR
References: