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

• Sponsor: Novartis Vaccines (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01636102
• Collaborator: (none)
• Enrollment: 126
• Location: 1
• Arm: 1

Study Details

Study Description

Brief Summary

To evaluate the safety of a single intramuscular (IM) injection of trivalent nonadjuvated influenza study vaccine, formulation 2012/2013, in adult and 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 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
Human Influenza	Biological: Trivalent influenza virus vaccine (TIV)	Phase 2

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 II Open Label, Uncontrolled, Multicenter Study to Evaluate Safety and Immunogenicity of a Surface Antigen, Inactivated, Influenza Vaccine (Agrippal®), Formulation 2012/2013, When Administered to Adult and Elderly Subjects
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1	Biological: Trivalent influenza virus vaccine (TIV); A single 0.5 mL dose of the study vaccine supplied in prefilled syringes and administered intramuscularly in the deltoid muscle of (preferably) the non dominant arm

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Who Achieved Seroconversion or Significant Increase in SRH Area Against Each of Three Vaccine Strains After One Vaccination of TIV [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 >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 TIV [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 >2.5 (≥18 years to ≤60 years) or >2.0 (≥61 years).

3. Percentage of Subjects Who Achieved SRH Area ≥25 mm2 Against Each of Three Vaccine Strains After One Vaccination of TIV [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 TIV vaccination (day 22). This criterion was met according to CHMP guideline if percentage of subjects achieving SRH area ≥25 mm2 is >70% (≥18 years to ≤60) or 60% (≥61 years).

Secondary Outcome Measures

1. Numbers 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 the TIV vaccination.

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, 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 (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. to eggs or eggs product as well as ovalbumin, chicken protein, chicken feathers, influenza viral protein, kanamycin and neomycin sulphate).

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 derivates 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 could have interfered with the safety of the subject.

3. Individuals who were 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, posed 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 were 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 who 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 were part of study personnel or close family members conducting this study.

6. BMI >35 kg/m2.

7. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Ghent, Center for Vaccinology, Prof.Dr. G Leroux Roels	Ghent		Belgium	BC001

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: NCT01636102
• Other Study ID Numbers: V71_32S; 2012-000063-24
• First Posted: Jul 10, 2012
• Last Update Posted: Nov 30, 2015
• Last Verified: Nov 1, 2015

• 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 1 site in Belgium.
Pre-assignment Detail	All subjects enrolled 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 TIV vaccination	Subjects ≥61 years of age who received one TIV vaccination
Period Title: Overall Study
STARTED	63	63
COMPLETED	63	63
NOT COMPLETED	0	0

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 TIV vaccination	Subjects ≥61 years of age who received one TIV vaccination	Total of all reporting groups
Overall Participants	63	63	126
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.9 (12.8)	69.2 (5.7)	53.6 (18.5)
Sex: Female, Male (Count of Participants)
Female	39 61.9%	26 41.3%	65 51.6%
Male	24 38.1%	37 58.7%	61 48.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Who Achieved Seroconversion or Significant Increase in SRH Area Against Each of Three Vaccine Strains After One Vaccination of TIV
Description	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 >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 TIV vaccination	Subjects ≥61 years of age who received one TIV vaccination
Measure Participants	62	62
A/H1N1	84	53
A/H3N2	81	65
B	69	73

2. Primary Outcome

Title	Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIV
Description	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 >2.5 (≥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 TIV vaccination	Subjects ≥61 years of age who received one TIV vaccination
Measure Participants	62	62
A/H1N1	5.7	2.88
A/H3N2	5.52	3.02
B	3.72	4.06

3. Primary Outcome

Title	Percentage of Subjects Who Achieved SRH Area ≥25 mm2 Against Each of Three Vaccine Strains After One Vaccination of TIV
Description	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 TIV vaccination (day 22). This criterion was met according to CHMP guideline if percentage of subjects achieving SRH area ≥25 mm2 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 TIV vaccination	Subjects ≥61 years of age who received one TIV vaccination
Measure Participants	62	62
A/H1N1 (Day 1)	34	27
A/H1N1 (Day 22)	95	71
A/H3N2 (Day 1)	23	45
A/H3N2 (Day 22)	85	92
B (Day 1)	61	21
B (Day 22)	97	82

4. Secondary Outcome

Title	Numbers 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 the TIV 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 TIV vaccination	Subjects ≥61 years of age who received one TIV vaccination
Measure Participants	62	63
Injection site pain	24	9
Injection site ecchymosis	0	1
Injection site erythema	3	4
Injection site induration	4	0
Injection site swelling	4	1
Chills/shivering	0	0
Malaise	2	1
Myalgia	5	3
Arthralgia	2	1
Headache	9	6
Sweating	3	2
Fatigue	8	3
Body temperature (≥38°C)	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 TIV vaccination		Subjects ≥61 years of age who received one TIV 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	28/63 (44.4%)		18/63 (28.6%)
General disorders
Fatigue	8/63 (12.7%)		3/63 (4.8%)
Injection Site Erythema	3/63 (4.8%)		5/63 (7.9%)
Injection Site Induration	4/63 (6.3%)		0/63 (0%)
Injection Site Pain	24/63 (38.1%)		10/63 (15.9%)
Injection Site Swelling	4/63 (6.3%)		1/63 (1.6%)
Musculoskeletal and connective tissue disorders
Myalgia	5/63 (7.9%)		3/63 (4.8%)
Nervous system disorders
Headache	9/63 (14.3%)		6/63 (9.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.