Safety and Immunogenicity of a Trivalent Influenza Vaccine When Administered to Elderly Subjects

• ClinicalTrials.gov Identifier: NCT01651104
• Recruitment Status: Completed
• First Posted: July 26, 2012
• Results First Posted: January 27, 2014
• Last Update Posted: April 21, 2014
• Sponsor: Novartis Vaccines
• Information provided by (Responsible Party): Novartis ( Novartis Vaccines )

Tracking Information

• First Submitted Date: July 24, 2012
• First Posted Date: July 26, 2012
• Results First Submitted Date: July 11, 2013
• Results First Posted Date: January 27, 2014
• Last Update Posted Date: April 21, 2014
• Study Start Date: July 2012
• Actual Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 19, 2013)

• Percentages of Subjects Who Achieved Seroconversion or Significant Increase in SRH Area Against Each of Three Vaccine Strains After One Vaccination of aTIV [ Time Frame: Day 22 ]
  Immunogenicity was measured as the percentage of subjects who achieved seroconversion or significant increase in single radial hemolysis (SRH) area, against each of three vaccine strains, three weeks after vaccination (day 22), evaluated using SRH assay. Seroconversion or significant increase in SRH area was defined as the percentage of subjects with a negative prevaccination serum (SRH area ≤4 mm2) to a postvaccination SRH area ≥25 mm2; or a significant increase in antibody titer from a non-negative prevaccination serum, i.e., at least a 50% increase in area. The European (CHMP) criterion is met if percentage of subjects achieving seroconversion or significant increase in SRH area is 30% (≥65 years).
• Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of aTIV [ Time Frame: Day 22 ]
  Geometric mean ratio (GMR) of subjects was calculated as the ratio of postvaccination to prevaccination SRH geometric mean areas (GMAs), directed against each of three vaccine strains, three weeks after vaccination (day 22). The CHMP criterion was met if the geometric mean increase (GMR, day 22/day 1) in SRH antibody area is >2.0 (≥65 years).
• Percentages of Subjects Who Achieved SRH Area ≥25 mm2 Against Each of Three Vaccine Strains After One Vaccination of aTIV [ Time Frame: Day 1 and 22 ]
  Immunogenicity was measured as the percentage of subjects achieving SRH area ≥25 mm2 against each of three vaccine strains at baseline (day 1) and three weeks after aTIV vaccination (day 22). This criterion is met according to CHMP guideline if percentage of subjects achieving SRH area ≥25 mm2 is 60% (≥65 years).

Original Primary Outcome Measures (submitted: July 24, 2012)

• Antibody response to each influenza vaccine antigen, as measured by single radial hemolysis (SRH) in elderly subjects. [ Time Frame: 21 days post vaccination ]
  In compliance with the requirements of the current EU recommendations for clinical trials related to yearly licensing of influenza vaccines.
• Hemagglutination inhibition (HI) [ Time Frame: 21 days postvaccination ]
• Local and systemic reactions [ Time Frame: For 3 days post the day of vaccination ]
• All adverse events [ Time Frame: 4 days (day 1 through day 4) ]
• Adverse events necessitating a physician's visit or consultation and/or leading to premature study discontinuation and SAEs [ Time Frame: Day 5 to end of study ]

Current Secondary Outcome Measures (submitted: December 19, 2013)

Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) [ Time Frame: From day 1 through day 4 postvaccination ]

Safety was assessed as the number of subjects who reported solicited local and systemic reactions from day 1 up to and including day 4 after the aTIV vaccination.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Immunogenicity of a Trivalent Influenza Vaccine When Administered to Elderly Subjects
• Official Title: A Phase 2, Open Label, Uncontrolled, Multicenter Study to Evaluate Safety and Immunogenicity of a Surface Antigen, Inactivated, Adjuvanted With MF59C.1 Influenza Vaccine (Fluad®), Formulation 2012/2013, When Administered to Elderly Subjects
• Brief Summary: To evaluate the safety of a single intramuscular (IM) injection of trivalent adjuvanted influenza study vaccine, formulation 2012/2013, in elderly subjects and the antibody response to each influenza vaccine antigen, as measured by single radial hemolysis (SRH) and hemagglutination inhibition (HI) at approximately 21 days postimmunization in elderly subjects in compliance with the requirements of the current EU recommendations for clinical trials related to yearly licensing of influenza vaccines.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Human Influenza

Intervention

Biological: Adjuvanted Trivalent Influenza Virus Vaccine (aTIV)

A single 0.5 mL dose of study vaccine supplied in prefilled syringes was administered intramuscularly in the deltoid muscle, preferably of the non dominant arm.

Study Arms

Experimental: Adjuvanted Trivalent Influenza Virus Vaccine

Intervention: Biological: Adjuvanted Trivalent Influenza Virus Vaccine (aTIV)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 24, 2012): 63
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 2012
• Actual Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male and female volunteers of 65 years of age or older, mentally competent, willing and able to give written informed consent prior to study entry;
2. Individuals able to comply 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 interfere 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 (ie. 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 have 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 would interfere 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, pose additional risk to the subjects due to participation in the study.

9. Individuals who within the past 6 months 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 are planning to receive any vaccine during the study.
11. Individuals with any acute or chronic infections requiring systemic antibiotic treatment or antiviral therapy within the last 7 days.
12. Individuals that have experienced fever (i.e., axillary temperature ≥38°C) within the last 3 days of intended study vaccination.
13. Individuals participating 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 65 Years and older (Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium

Administrative Information

• NCT Number: NCT01651104
• Other Study ID Numbers: V70_39S; 2012-000085-38 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Novartis ( Novartis Vaccines )
• Study Sponsor: Novartis Vaccines
• Collaborators: Not Provided

Investigators

• Study Chair: Novartis Vaccines and Diagnostics; Novartis Vaccines

• PRS Account: Novartis
• Verification Date: April 2014