Study to Evaluate Safety and Immunogenicity of Sub-unit Adjuvanted Influenza Vaccine Administered to Elderly Subjects, Formulation 2011-2012

• Sponsor: Novartis Vaccines (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01344057
• Collaborator: (none)
• Enrollment: 63
• Locations: 6
• Arm: 1
• Duration (Months): 1
• Patients Per Site: 10.5
• Patients Per Site Per Month: 10.3

Study Details

Study Description

Brief Summary

This study will evaluate the safety and immunogenicity of a sub-unit, adjuvanted Influenza Vaccine Administered to Elderly Subjects.

Condition or Disease	Intervention/Treatment	Phase
Seasonal Influenza	Biological: Seasonal Influenza Vaccine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase II, Open Label, Uncontrolled, Multi Center Study to Evaluate Safety and Immunogenicity of a Surface Antigen, Inactivated, Adjuvanted With MF59C.1 Influenza Vaccine, Formulation 2011-2012, When Administered to Elderly Subjects
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Other: Sub unit, Inactivated, MF59C.1 Adjuvanted Influenza Vaccine No comparator is administered, only one IM single dose of trivalent subunit inactivated influenza vaccine is administered during the vaccination visit	Biological: Seasonal Influenza Vaccine; This phase II is performed as a multicenter study in elderly subjects. Enrolled subjects received one single IM dose of trivalent subunit inactivated adjuvanted flu vaccine during the vaccination visit, according to the study protocol (follow-up period: until day 22) .

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved Seroconversion or Significant Increase in Single Radial Hemolysis (SRH) Area Against Each of Three Vaccine Strains After One Vaccination of FLUAD [day 22]

   Immunogenicity was measured as the percentage of participants who achieved seroconversion or significant increase in single radial hemolysis (SRH) area, against each of the three vaccine strains, three weeks after vaccination (day 22), evaluated using SRH assay. Seroconversion: proportion of participants with negative pre-vaccination serum and a post-vaccination serum area ≥ 25 mm2. Significant increase: proportion of participants with at least a 50% increase in area from positive pre-vaccination serum. Seroconversion or significant increase: proportion of participants with either seroconversion or significant increase. The European (Committee for Medicinal Products for Human Use [CHMP]) criterion is met, if percentage of participants achieving seroconversion or significant increase in SRH area is 30% (≥65 years).

2. Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD [day 22]

   Geometric mean ratio (GMR) of participants was calculated as the ratio of post-vaccination to pre-vaccination SRH geometric mean areas (GMAs), directed against each of the three vaccine strains, three weeks after FLUAD 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).

3. Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD [day 22]

   Immunogenicity was measured as the percentage of participants achieving SRH area ≥25 mm2 against each of the three vaccine strains at baseline (day 1) and three weeks after FLUAD vaccination (day 22). This criterion is met according to CHMP guideline if percentage of participants achieving SRH area ≥25 mm2 is 60% (≥65 years).

Secondary Outcome Measures

1. Number of Participants Who Reported Solicited Local and Systemic Reactions [1 to 4 days post-vaccination]

   Safety was assessed for participants who reported solicited local and systemic reactions from day 1 up to and including day 4 after the FLUAD vaccination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Key Inclusion Criteria:

• Males and females volunteers of 65 years of age or older, mentally competent, willing and able to give written informed consent prior to study entry.

• Individuals able to comply with all the study requirements.

• Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.

• Written informed consent must be obtained for all the subjects before enrollment into the study after the nature of the study has been explained.

Key Exclusion Criteria:

• Individuals with any serious chronic or acute disease.

• Individuals with history of any anaphylactic reaction and/or serious allergic reaction following a vaccination.

• Individuals with known or suspected impairment/alteration of immune function.

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

• 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.

• Individuals within the past 6 months, they have: had any seasonal or pandemic laboratory confirmed influenza disease; received any seasonal or pandemic influenza vaccine.

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

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

• 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.

• Individuals who received any other vaccines within 4 weeks prior to enrollment in this study or who are planning to receive any vaccine within 4 weeks from the study vaccines.

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

• BMI > 35 kg/m2.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dipartimento di Medicina e Scienze dell'Invecchiamento, Università G. D'Annunzio	Via dei Vestini	Chieti	Italy	66100
2	Department of "Scienze della Salute" University of Genova Via Pastore 1	Genova		Italy	16132
3	Satellite: "ASL Lanciano - Vasto", sede legale Via S Spaventa 37	Lanciano		Italy	66034
4	Satellite: "Distretto Sanitario di Base di Fossacesia" in Via Polidoro-Vasto	Lanciano		Italy
5	Vaccine and Immunotherapy Research Center Department of Infectious and Tropical Diseases San Raffaele Scientific Institute Via Stamira d'Ancona 20	Milano		Italy	20127
6	Department of "malattie infettive" Ospedale San Gerardo, via Pergolesi 33	Monza		Italy	20052

Sponsors and Collaborators

• Novartis Vaccines

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Vaccines
• ClinicalTrials.gov Identifier: NCT01344057
• Other Study ID Numbers: V70_32S; 2010-021841-38
• First Posted: Apr 28, 2011
• Last Update Posted: Jan 28, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Novartis Vaccines: Seasonal Influenza, vaccine
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	Overall, 63 participants were ≥65 years of age were enrolled at 4 sites in Italy.
Pre-assignment Detail	Blood sample for immunogenicity assays were collected before vaccination (Day 1) and after 21 Days.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single intramuscular (IM) dose of 0.5 milliliter (mL) of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until day 22.
Period Title: Overall Study
STARTED	63
COMPLETED	62
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM dose of 0.5 mL of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until day 22.
Overall Participants	63
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	73.2 (5.2)
Sex: Female, Male (Count of Participants)
Female	31 49.2%
Male	32 50.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved Seroconversion or Significant Increase in Single Radial Hemolysis (SRH) Area Against Each of Three Vaccine Strains After One Vaccination of FLUAD
Description	Immunogenicity was measured as the percentage of participants who achieved seroconversion or significant increase in single radial hemolysis (SRH) area, against each of the three vaccine strains, three weeks after vaccination (day 22), evaluated using SRH assay. Seroconversion: proportion of participants with negative pre-vaccination serum and a post-vaccination serum area ≥ 25 mm2. Significant increase: proportion of participants with at least a 50% increase in area from positive pre-vaccination serum. Seroconversion or significant increase: proportion of participants with either seroconversion or significant increase. The European (Committee for Medicinal Products for Human Use [CHMP]) criterion is met, if percentage of participants achieving seroconversion or significant increase in SRH area is 30% (≥65 years).
Time Frame	day 22

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set included all enrolled participants who had correctly received the vaccine, provided evaluable serum samples before and after vaccination, and had no major protocol violations.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM dose of 0.5 mL of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until day 22.
Measure Participants	63
A/H1N1 (N= 62)	69 109.5%
A/H3N2 (N= 62)	50 79.4%
B (N= 62)	26 41.3%

2. Secondary Outcome

Title	Number of Participants Who Reported Solicited Local and Systemic Reactions
Description	Safety was assessed for participants who reported solicited local and systemic reactions from day 1 up to and including day 4 after the FLUAD vaccination.
Time Frame	1 to 4 days post-vaccination

Outcome Measure Data

Analysis Population Description

Analysis was done using the safety dataset; participants who received study vaccination and who provided post-vaccination safety data.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM dose of 0.5 mL of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until day 22.
Measure Participants	63
Injection site ecchymosis (N= 62)	3 4.8%
Injection site erythema (N= 62)	7 11.1%
Injection site induration (N= 62)	4 6.3%
Injection site swelling (N= 62)	7 11.1%
Injection site pain (N= 62)	21 33.3%
Chills Shivering (N= 62)	4 6.3%
Malaise (N= 62)	3 4.8%
Myalgia (N= 62)	6 9.5%
Arthralgia (N= 62)	4 6.3%
Headache (N= 62)	4 6.3%
Sweating (N= 62)	1 1.6%
Fatigue (N= 62)	2 3.2%
Fever (≥38°C) (N= 61)	0 0%

3. Primary Outcome

Title	Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD
Description	Geometric mean ratio (GMR) of participants was calculated as the ratio of post-vaccination to pre-vaccination SRH geometric mean areas (GMAs), directed against each of the three vaccine strains, three weeks after FLUAD 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).
Time Frame	day 22

Outcome Measure Data

Analysis Population Description

Analysis was done using PP set.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM dose of 0.5 mL of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until day 22.
Measure Participants	63
A/H1N1 (N= 62)	2.54
A/H3N2 (N= 62)	1.9
B (N= 62)	1.36

4. Primary Outcome

Title	Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD
Description	Immunogenicity was measured as the percentage of participants achieving SRH area ≥25 mm2 against each of the three vaccine strains at baseline (day 1) and three weeks after FLUAD vaccination (day 22). This criterion is met according to CHMP guideline if percentage of participants achieving SRH area ≥25 mm2 is 60% (≥65 years).
Time Frame	day 22

Outcome Measure Data

Analysis Population Description

Analysis was done using PP set.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM dose of 0.5 mL of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until day 22.
Measure Participants	63
A/H1N1 (N= 62)	89 141.3%
A/H3N2 (N= 62)	69 109.5%
B (N= 62)	94 149.2%

Adverse Events

Time Frame	From Day 1 through Day 22.
Adverse Event Reporting Description	Adverse events other than local and systemic reactions or solicited reactions lasting longer than 3 days after vaccination were documented during the study period.
Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of trivalent subunit inactivated adjuvanted influenza vaccine FLUAD during the vaccination visit, according to the study protocol (follow-up period: until day 22).
All Cause Mortality
	FLUAD
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	FLUAD
	Affected / at Risk (%)	# Events
Total	0/63 (0%)
Other (Not Including Serious) Adverse Events
	FLUAD
	Affected / at Risk (%)	# Events
Total	6/63 (9.5%)
General disorders
Injection site erythema	3/63 (4.8%)
Injection site haemorrhage	2/63 (3.2%)
Injection site induration	2/63 (3.2%)
Injection site pain	2/63 (3.2%)
Injection site swelling	2/63 (3.2%)
Infections and infestations
Mastoiditis	1/63 (1.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/63 (3.2%)
Myalgia	2/63 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreement with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publications of the pooled data (i.e., data from all sites) in the clinical trial.