Safety and Immunogenicity of a Surface Antigen, Inactivated, Adjuvanted With MF59C.1, Seasonal Influenza Vaccine, Formulation 2009-2010

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00956761
• Collaborator: Novartis Vaccines (Industry)
• Enrollment: 63
• Locations: 2
• Arm: 1
• Patients Per Site: 31.5

Study Details

Study Description

Brief Summary

This is a trial for annual registration of the updated seasonal influenza vaccine formulation.

Condition or Disease	Intervention/Treatment	Phase
Seasonal Influenza	Biological: Seasonal Influenza Vaccine (MF59C.1)	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 FLUAD® Surface Antigen, Inactivated, Adjuvanted With MF59C.1 Influenza Vaccine, Formulation 2009-2010, When Administered to Elderly Subjects
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Biological: Seasonal Influenza Vaccine (MF59C.1); 1 dose of a surface antigen, inactivated, adjuvanted with MF59C.1, seasonal influenza vaccine, formulation 2009-2010

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 21]

   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 21), 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 21]

   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 21). The CHMP criterion was met if the geometric mean increase (GMR, day 21/day 0) 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 21]

   Immunogenicity was measured as the percentage of participants achieving SRH area ≥25 mm2 against each of the three vaccine strains at baseline (day 0) and three weeks after FLUAD vaccination (day 21). This criterion is met according to CHMP guideline if percentage of participants achieving SRH area ≥25 mm2 is 60% (≥65 years).

4. Number of Participants Who Reported Solicited Local and Systemic Reactions [0-3 days post-vaccination]

   Safety was assessed for participants who reported solicited local and systemic reactions from day 0 up to and including day 3 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:

• Subjects of 65 years of age or older

• Mentally competent

• Willing and able to give written informed consent prior to study entry

• Able to comply with all the study requirements

• In general good health

Key Exclusion Criteria:

• Any serious chronic or acute disease disease

• History of any anaphylactic reaction and/or serious allergic reaction following a vaccination

• A proven hypersensitivity to any component of the study vaccine

• Known or suspected (or have a high risk of developing) impairment/alteration of immune function (excluding that normally associated with advanced age)

• Bleeding diathesis or conditions associated with prolonged bleeding time that in the investigator's opinion would interfere with the safety of the subject

• Within the past 12 months, participants had received more than one injection of influenza vaccine

• Within the past 6 months, participants had laboratory confirmed influenza disease or received influenza vaccine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 2: Ufficio Igiene e Sanità Pubblica di Lanciano, ASL Lanciano - Vasto, sede legale Via S. Spaventa, 37	Lanciano		Italy	66034
2	Site 3: Pianiga Distretto n. 2 - Area Sud - Azienda ULSS 13 Mirano-Via Nazionale 48	Pianiga		Italy	30034

Sponsors and Collaborators

• Novartis
• Novartis Vaccines

Investigators

• Study Chair: Novartis Vaccines, Novartis Vaccines

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT00956761
• Other Study ID Numbers: V70_09S; 2009-010586-23
• First Posted: Aug 11, 2009
• Last Update Posted: Jan 27, 2016
• Last Verified: Dec 1, 2015

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

Study Results

Participant Flow

Recruitment Details	Overall, 63 participants ≥65 years of age were enrolled at 2 sites in Italy.
Pre-assignment Detail	Blood samples for the determination of antibody titers were drawn on Day 0 prior to vaccination.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single intramuscular (IM) 0.5 milliliter (mL) dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2009/2010 influenza season, into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Period Title: Overall Study
STARTED	63
COMPLETED	63
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2009/2010 influenza season, into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Overall Participants	63
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	72.9 (6.0)
Sex: Female, Male (Count of Participants)
Female	27 42.9%
Male	36 57.1%

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 21), 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 21

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set included all enrolled participants who had received the relevant dose of vaccine correctly on Day 0, provided evaluable serum samples with the relevant time windows, and had no major protocol violations.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2009/2010 influenza season, into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Measure Participants	61
A/H1N1	43 68.3%
A/H3N2	46 73%
B	43 68.3%

2. 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 21). The CHMP criterion was met if the geometric mean increase (GMR, day 21/day 0) in SRH antibody area is >2.0 (≥65 years).
Time Frame	day 21

Outcome Measure Data

Analysis Population Description

Analysis was done using PP set.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2009/2010 influenza season, into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Measure Participants	61
A/H1N1	1.55
A/H3N2	1.53
B	1.59

3. 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 0) and three weeks after FLUAD vaccination (day 21). This criterion is met according to CHMP guideline if percentage of participants achieving SRH area ≥25 mm2 is 60% (≥65 years).
Time Frame	day 21

Outcome Measure Data

Analysis Population Description

Analysis was done using PP set.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2009/2010 influenza season, into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Measure Participants	61
A/H1N1	93 147.6%
A/H3N2	93 147.6%
B	98 155.6%

4. Primary 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 0 up to and including day 3 after the FLUAD vaccination.
Time Frame	0-3 days post-vaccination

Outcome Measure Data

Analysis Population Description

Analysis was done using the safety dataset; participants in the exposed population who provided post-vaccination safety data.

Arm/Group Title	FLUAD
Arm/Group Description	Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2009/2010 influenza season, into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 3.
Measure Participants	63
Injection site ecchymosis	2 3.2%
Injection site erythema	8 12.7%
Injection site induration	3 4.8%
Injection site swelling	6 9.5%
Injection site pain	9 14.3%
Chills Shivering	1 1.6%
Malaise	1 1.6%
Myalgia	0 0%
Arthralgia	1 1.6%
Headache	5 7.9%
Sweating	0 0%
Fatigue	1 1.6%
Fever (≥38°C)	0 0%

Adverse Events

Time Frame	From Day 0 through Day 21.
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 FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2009/2010 influenza season, into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
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	2/63 (3.2%)
General disorders
Injection site ecchymosis	1/63 (1.6%)
Injection site erythema	1/63 (1.6%)
Injection site induration	1/63 (1.6%)

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.