Clinical trial NCT01640327: Safety and Immunogenicity of One Dose of Seasonal Trivalent Influenza Virus Vaccine (TIVf, Purified Surface Antigen, Inactivated, Egg Derived) in Adults Aged 18 Years and Above
Official title: A Phase 3, Open Label, Uncontrolled, Multicenter Study to Evaluate Safety and Immunogenicity of a Surface Antigen, Inactivated, Influenza Vaccine (Fluvirin®), Formulation 2012/2013, When Administered to Adult and Elderly Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Human
Influenza
Keywords: Interpandemic influenza
Adult
Elderly
Safety
Tolerability
Immunology
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-07-13
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This protocol was designed to evaluate the safety, clinical tolerability and immunogenicity of the Trivalent Influenza Virus Vaccine (TIVf, purified surface antigen, inactivated, egg derived), Northern Hemisphere formulation 2012/2013. The principal aim was to provide safety and immunogenicity data, in compliance to current EU Guidelines, with the intent of obtaining marketing approval of the vaccine formulation intended for use prior to the next influenza season in the Northern Hemisphere.

The antibody response to each influenza vaccine antigen, was measured by hemagglutination inhibition (HI) and single radial hemolysis (SRH) at approximately 21 days postimmunization in adult and elderly subjects. The safety and immunogenicity of a single intramuscular (IM) injection of the vaccine was evaluated in compliance with the requirements of the current EU recommendations for clinical trials related to yearly licensing of influenza vaccines (CPMP/BWP/214/96).


Eligibility criteria: Inclusion Criteria:

1. Male and female volunteers of 18 years of age or older, mentally competent, were willing and gave written informed consent prior to study entry;
2. Individuals who complied with all the study requirements;
3. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.

Exclusion Criteria:

1. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, could have interfered with the subject's ability to participate in the study.
2. Individuals with any serious chronic or acute disease (in the judgment of the investigator), including but not limited to:

   * Medically significant cancer (except for benign or localized skin cancer, cancer in remission for ≥10 years or localized prostate cancer that has been clinically stable for more than 2 years without treatment);
   * Medically significant advanced congestive heart failure (i.e., NYHA class III and IV);
   * Chronic obstructive pulmonary disease (COPD; i.e., GOLD Stage III and IV);
   * Autoimmune disease (including rheumatoid arthritis, except for Hashimoto's thyroiditis that has been clinically stable for ≥5 years);
   * Diabetes mellitus type I;
   * Poorly controlled diabetes mellitus type II;
   * Advanced arteriosclerotic disease;
   * History of underlying medical condition such as major congenital abnormalities requiring surgery, chronic treatment, or associated with developmental delay (e.g., Down's syndrome);
   * Acute or progressive hepatic disease;
   * Acute or progressive renal disease;
   * Severe neurological (es. Guillain-Barré syndrome) or psychiatric disorder;
   * Severe asthma.
3. Individuals with history of any anaphylactic reaction and/or serious allergic reaction following a vaccination, a proven hypersensitivity to any component of the study vaccine (e.g. to eggs or eggs product as well as ovalbumin, chicken protein, chicken feathers, influenza viral protein, kanamycin and neomycin sulphate).
4. Individuals with known or suspected (or had a high risk of developing) impairment/alteration of immune function (excluding that normally associated with advanced age) resulting, for example, from:

   * receipt of immunosuppressive therapy (any parenteral or oral corticosteroid or cancer chemotherapy/radiotherapy) within the past 60 days and for the full length of the study;
   * receipt of immunostimulants;
   * receipt of parenteral immunoglobulin preparation, blood products and/or plasma derivates within the past 3 months and for the full length of the study;
   * suspected or known HIV infection or HIV-related disease.
5. Individuals with known or suspected history of drug or alcohol abuse.
6. Individuals with a bleeding diathesis or conditions associated with prolonged bleeding time that in the investigator's opinion could have interfered with the safety of the subject.
7. Individuals who were not able to comprehend and to follow all required study procedures for the whole period of the study.
8. Individuals with history or any illness that, in the opinion of the investigator, posed additional risk to the subjects due to participation in the study.
9. Individuals who within the past 6 months (prior to study enrollement) have:

   * had any laboratory confirmed seasonal or pandemic influenza disease;
   * received any seasonal or pandemic influenza vaccine.
10. Individuals who received any other vaccine within 4 weeks prior to enrollment in this study or who were planning to receive any vaccine during the study.
11. Individuals with any acute or chronic infections required systemic antibiotic treatment or antiviral therapy within the last 7 days.
12. Individuals who had experienced fever (i.e., axillary temperature ≥38°C) within the last 3 days of intended study vaccination.
13. Individuals who participated in any clinical trial with another investigational product 4 weeks prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study.
14. Individuals who were part of study personnel or close family members conducting this study.
15. BMI \>35 kg/m2.
16. Females who were pregnant (confirmed by positive urine pregnancy test) or nursing (breastfeeding). Females of childbearing potential who refused to use an acceptable method of birth control for the whole duration of the study.

Primary outcomes:
measure: Percentage of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVf
timeFrame: Day 22
measure: Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVf
timeFrame: Day 22
measure: Percentage of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVf
timeFrame: Day 1 and 22
Secondary outcomes:
measure: Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination)
timeFrame: From day 1 through day 4 postvaccination
Other outcomes:
Locations:
city: Rostock
country: Germany
facility: University of Rostock, Department Tropical Medicine and Infectious Diseases
state: Mecklenburg-Western Pomerania
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines and Diagnostics
role: STUDY_CHAIR
References: