Safety and Immunogenicity of a Cell Derived Subunit Trivalent Nonadjuvated Influenza Study Vaccine in Adults Aged 18 Years and Above

• Sponsor: Novartis Vaccines (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01640314
• Collaborator: (none)
• Enrollment: 126
• Location: 1
• Arm: 1
• Duration (Months): 1
• Patients Per Site Per Month: 123.7

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety of a single intramuscular (IM) injection of the cell derived subunit trivalent nonadjuvanted influenza vaccine in adult and elderly subjects and the antibody response to each influenza vaccine antigen, as measured by hemagglutination inhibition (HI) at approximately 21 days postimmunization in adult and elderly subjects in compliance with the requirements of the current EU recommendations for clinical trials related to yearly licensing of influenza vaccines.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: Cell derived subunit trivalent nonadjuvanted vaccine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 126 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 3 Open Label, Uncontrolled, Multi Center Study to Evaluate Safety and Immunogenicity of a Surface Antigen, Inactivated, Influenza Vaccine Produced in Mammalian Cell Culture (Optaflu®), Formulation 2012/2013, When Administered to Adult and Elderly Subjects
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cell derived subunit trivalent nonadjuvanted vaccine	Biological: Cell derived subunit trivalent nonadjuvanted vaccine; A single 0.5 mL dose of the cell derived subunit trivalent nonadjuvated influenza vaccine (TIVc) supplied in prefilled syringes and administered intramuscularly in the deltoid muscle (preferably) of the non dominant arm.

Outcome Measures

Primary Outcome Measures

1. Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc [Day 22]

   Immunogenicity was measured as the percentage of subjects who achieved seroconversion or significant increase in hemagglutination inhibition (HI) titer, against each of three vaccine strains, three weeks after vaccination (day 22), evaluated using HI cell-derived antigen assay. As per the European (CHMP) criteria, seroconversion or significant increase in titer is defined as the percentage of subjects with a prevaccination HI titer <10 to a postvaccination HI titer ≥40; or in subjects with a prevaccination HI titer ≥10, a ≥4-fold increase in postvaccination HI antibody titer. This criterion is met according to CHMP guideline if percentage of subjects achieving seroconversion or significant increase in HI titer is >40% (≥18 years to ≤60 years) or 30% (≥61 years).

2. Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc [Day 22]

   Geometric mean ratio (GMR) of subjects was calculated as the ratio of postvaccination to prevaccination HI geometric mean titers (GMTs), 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 HI antibody titer is >2.5 (≥18 years to ≤60 years) or >2.0 (≥61 years).

3. Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc [Day 1 and 22]

   Immunogenicity was measured as the percentage of subjects achieving HI titer ≥40 against each of three vaccine strains at baseline (day 1) and three weeks after TIVc vaccination (day 22). This criterion was met according to CHMP guideline if percentage of subjects achieving HI titer ≥40 is >70% (≥18 years to ≤60) or 60% (≥61 years).

Secondary Outcome Measures

1. Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) [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 TIVc vaccination.

2. Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. [Day 1 to Day 22]

   The number of subjects in both age groups reporting any unsolicited AEs between Day 1 to Day 22 after receiving one dose of TIVc.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Male and female volunteers of 18 years of age or older;

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, may 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.

1. 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.Influenza viral protein).

2. 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 derivatives within the past 3 months and for the full length of the study;

• suspected or known HIV infection or HIV-related disease.

1. Individuals with known or suspected history of drug or alcohol abuse.

2. 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.

3. Individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study.

4. 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.

5. Individuals who within the past 6 months have:

• had any laboratory confirmed seasonal or pandemic influenza disease;

• received any seasonal or pandemic influenza vaccine.

1. 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.

2. Individuals with any acute or chronic infections requiring systemic antibiotic treatment or antiviral therapy within the last 7 days.

3. Individuals that have experienced fever (i.e., axillary temperature ≥38°C) within the last 3 days of intended study vaccination.

4. 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.

5. Individuals who are part of study personnel or close family members conducting this study.

6. BMI >35 kg/m2.

7. Females who are pregnant (confirmed by positive urine pregnancy test) or nursing (breastfeeding). Females of childbearing potential who refuse to use an acceptable method of birth control for the whole duration of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bernhard Nocht Institute	Bernhard-Nocht-Strasse 74	Hamburg	Germany	D-20359

Sponsors and Collaborators

• Novartis Vaccines

Investigators

• Study Chair: Novartis Vaccines and Diagnostics, Novartis Vaccines

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Vaccines
• ClinicalTrials.gov Identifier: NCT01640314
• Other Study ID Numbers: V58_32S; 2011-006277-25
• First Posted: Jul 13, 2012
• Last Update Posted: Feb 17, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by Novartis Vaccines: Influenza; Adults; Elderly; Immunology; Safety
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at one study centre in Germany.
Pre-assignment Detail	All enrolled subjects were included in the trial.

Arm/Group Title	18-60 Y	≥ 61 Y
Arm/Group Description	Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	Subjects ≥61 years of age who received one TIVc vaccination
Period Title: Overall Study
STARTED	63	63
COMPLETED	63	62
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	18-60 Y	≥ 61 Y	Total
Arm/Group Description	Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	Subjects ≥61 years of age who received one TIVc vaccination	Total of all reporting groups
Overall Participants	63	63	126
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.4 (11.4)	68.0 (4.7)	52.7 (17.7)
Sex: Female, Male (Count of Participants)
Female	33 52.4%	31 49.2%	64 50.8%
Male	30 47.6%	32 50.8%	62 49.2%

Outcome Measures

1. Primary Outcome

Title	Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc
Description	Immunogenicity was measured as the percentage of subjects who achieved seroconversion or significant increase in hemagglutination inhibition (HI) titer, against each of three vaccine strains, three weeks after vaccination (day 22), evaluated using HI cell-derived antigen assay. As per the European (CHMP) criteria, seroconversion or significant increase in titer is defined as the percentage of subjects with a prevaccination HI titer <10 to a postvaccination HI titer ≥40; or in subjects with a prevaccination HI titer ≥10, a ≥4-fold increase in postvaccination HI antibody titer. This criterion is met according to CHMP guideline if percentage of subjects achieving seroconversion or significant increase in HI titer is >40% (≥18 years to ≤60 years) or 30% (≥61 years).
Time Frame	Day 22

Outcome Measure Data

Analysis Population Description

Analysis was done on the per-protocol (PP) set, i.e. the subjects who received the vaccine correctly; provided evaluable serum samples at the relevant time points; and had no major protocol violations as defined prior to analysis.

Arm/Group Title	18-60 Y	≥ 61 Y
Arm/Group Description	Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	Subjects ≥61 years of age who received one TIVc vaccination
Measure Participants	63	62
A/H1N1	73	58
A/H3N2	67	45
B	63	42

2. Primary Outcome

Title	Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc
Description	Geometric mean ratio (GMR) of subjects was calculated as the ratio of postvaccination to prevaccination HI geometric mean titers (GMTs), 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 HI antibody titer is >2.5 (≥18 years to ≤60 years) or >2.0 (≥61 years).
Time Frame	Day 22

Outcome Measure Data

Analysis Population Description

Analysis was done on the PP set.

Arm/Group Title	18-60 Y	≥ 61 Y
Arm/Group Description	Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	Subjects ≥61 years of age who received one TIVc vaccination
Measure Participants	63	62
A/H1N1	13	5.79
A/H3N2	6.38	4.21
B	5.63	3.54

3. Primary Outcome

Title	Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc
Description	Immunogenicity was measured as the percentage of subjects achieving HI titer ≥40 against each of three vaccine strains at baseline (day 1) and three weeks after TIVc vaccination (day 22). This criterion was met according to CHMP guideline if percentage of subjects achieving HI titer ≥40 is >70% (≥18 years to ≤60) or 60% (≥61 years).
Time Frame	Day 1 and 22

Outcome Measure Data

Analysis Population Description

Analysis was done on the PP set.

Arm/Group Title	18-60 Y	≥ 61 Y
Arm/Group Description	Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	Subjects ≥61 years of age who received one TIVc vaccination
Measure Participants	63	62
A/H1N1 (Day 1)	56	61
A/H1N1 (Day 22)	98	100
A/H3N2 (Day 1)	86	85
A/H3N2 (Day 22)	100	100
B (Day 1)	54	40
B (Day 22)	98	85

4. Secondary Outcome

Title	Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination)
Description	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 TIVc vaccination.
Time Frame	From day 1 through day 4 postvaccination

Outcome Measure Data

Analysis Population Description

Analysis was done on the safety dataset i.e. the subjects in the exposed population who provided postvaccination safety data.

Arm/Group Title	18-60 Y	≥ 61 Y
Arm/Group Description	Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	Subjects ≥61 years of age who received one TIVc vaccination
Measure Participants	63	63
Injection site ecchymosis	1	4
Injection site erythema	1	0
Injection site swelling	1	2
Injection site induration	0	2
Injection site pain	29	17
Chills/shivering	1	1
Malaise	5	2
Myalgia	27	12
Arthralgia	2	0
Headache	13	4
Sweating	10	7
Fatigue	15	7
Fever (≥38°C)	0	0

5. Secondary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc.
Description	The number of subjects in both age groups reporting any unsolicited AEs between Day 1 to Day 22 after receiving one dose of TIVc.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Analysis was done on the safety set population.

Arm/Group Title	18-60 Y	≥ 61 Y
Arm/Group Description	Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	Subjects ≥61 years of age who received one TIVc vaccination
Measure Participants	63	63
Any AEs	9	12
At least possibly related AEs	5	7
Serious AEs	0	0
At least possibly related SAEs	0	0
AEs leading to withdrawal	0	0

Adverse Events

Time Frame	From day 1 through day 22
Adverse Event Reporting Description	Serious adverse events (SAEs) were collected from day 1 through day 22.
Arm/Group Title	18-60 Y		≥ 61 Y
Arm/Group Description	Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination		Subjects ≥61 years of age who received one TIVc vaccination
All Cause Mortality
	18-60 Y		≥ 61 Y
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	18-60 Y		≥ 61 Y
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/63 (0%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	18-60 Y		≥ 61 Y
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/63 (71.4%)		30/63 (47.6%)
General disorders
Fatigue	15/63 (23.8%)	15	7/63 (11.1%)	7
Injection site haemorrhage	1/63 (1.6%)	1	4/63 (6.3%)	4
Injection site pain	29/63 (46%)	29	17/63 (27%)	17
Malaise	5/63 (7.9%)	5	2/63 (3.2%)	2
Musculoskeletal and connective tissue disorders
Myalgia	27/63 (42.9%)	27	12/63 (19%)	12
Nervous system disorders
Headache	13/63 (20.6%)	13	4/63 (6.3%)	4
Skin and subcutaneous tissue disorders
Hyperhidrosis	10/63 (15.9%)	10	7/63 (11.1%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.